Bruce Jancin

 

EXPERT ANALYSIS FROM THE NORTHWESTERN VASCULAR SYMPOSIUM

CHICAGO – Postoperative ischemic colitis after abdominal aortic aneurysm (AAA) repair is a feared, potentially devastating complication with a mortality approaching 50%, but early diagnosis can mitigate that risk, Roy M. Fujitani, MD, said at a symposium on vascular surgery sponsored by Northwestern University in Chicago.

Bruce Jancin/Frontline Medical News

The key is to be familiar with the risk factors for this complication. Close surveillance of patients with multiple risk factors is particularly important for the first 4 days after AAA repair since more than three-quarters of cases are diagnosed in this time frame, according to Dr. Fujitani, professor and vice chair of surgery at University of California, Irvine.

The most common etiology of ischemic colitis following AAA repair is hypoperfusion of the mesenteric vasculature leading to nonocclusive ischemia. Caught early – in the initial hyperactive phase of colonic ischemia – the complication is typically transient and can be managed medically without further sequelae. Improvement is generally noted within a day or 2, with complete resolution within 1-2 weeks.

The earliest indicator that a patient is in the hyperactive phase of ischemic colitis following completion of an AAA repair can be defecation while still on the operating table.

“When you’ve just completed an operation and the patient has a bowel movement right on the operating table, that always makes me very, very concerned because of the likelihood of an associated ischemic colitis,” the surgeon noted.

A conscious patient in the first phase of ischemic colitis will describe an urgent desire to defecate, along with crampy pain and loose bowel movements with or without blood in the stool.

In the second, paralytic phase of ischemic colitis, the pain diminishes in intensity but becomes more continuous and diffuse, usually in the lateral borders of the abdomen. The abdomen becomes distended and much more tender, and there are no bowel sounds.

In patients whose ischemic colitis has been misdiagnosed or undiagnosed, the shock phase comes next. This is marked by massive fluid, protein, and electrolyte loss through the gangrenous mucosa. The result is severe dehydration, metabolic acidosis, and hypovolemic shock.

Nonocclusive colonic ischemia most often affects the watershed areas of the colon, such as the Sudeck point at the rectosigmoid junction.

The two other etiologies of ischemic colitis occurring as a complication of AAA repair are acute arterial occlusion, typically caused by iatrogenic embolization from a proximal source, often during endovascular aneurysm repair (EVAR), or rarely, venous thrombosis.
 

Making the diagnosis

When a patient is suspected of having ischemic colitis, one of the easiest ways of advancing toward a diagnosis is to obtain an abdominal plain x-ray, which classically shows thumb printing indicative of submucosal edema. CT with IV contrast typically shows bowel wall thickening, pericolonic fat stranding, and – most significantly – there may be free air within the colonic wall, an indicator of more advanced ischemia that occurs shortly before transmural gangrenous changes.

Colonoscopy is, however, the mainstay of diagnosis. It should be performed in any patient where postoperative ischemic colitis is suspected.
 

Ischemic colitis risk factors and outcomes

Dr. Fujitani was senior author of the largest ever study of risk factors for and outcomes of postoperative ischemic colitis in patients undergoing contemporary methods of open and endovascular AAA repair. This retrospective analysis of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database included 3,486 patients who underwent AAA repair in U.S. hospitals during 2011-2012. Twelve percent had an open repair, while the other 88% underwent EVAR.

The incidence of postoperative ischemic colitis was 2.2%. The median time of diagnosis was on postoperative day 2. The rate was nearly threefold higher in the open repair group: 5.2% versus 1.8%. However, the open-repair group had a higher rate of emergency admission, ruptured aneurysm before surgery, and other high-risk features. Upon multivariate analysis, the adjusted risk of postoperative ischemic colitis was no longer significantly different in the open-repair and EVAR groups.

The mean hospital length of stay in patients with postoperative ischemic colitis was 20 days, compared with 5 days in those without the complication. The unadjusted in-hospital mortality rate in patients with ischemic colitis was 39% versus 4% in those without ischemic colitis.

Of the 75 patients who developed postoperative ischemic colitis, 37 were managed medically, 38 surgically.

“What was quite surprising was that there was a 56.8% in-hospital mortality in the surgically treated patients. The point being that if you end up having ischemic colitis, there’s a 50% chance you’ll end up requiring an operation, and if you do undergo an operation you have more than a 50% chance of succumbing from the process,” Dr. Fujitani observed.

Dr. Fujitani and his coinvestigators scrutinized a plethora of potential risk factors for postoperative ischemic colitis. Six emerged as significant upon multivariate analysis: ruptured aneurysm before surgery, with an associated adjusted 4.1-fold increased risk; need for intra- or postoperative transfusion, with a 6-fold increased risk; renal failure requiring dialysis, with a 3.9-fold risk; proximal extension of the aneurysm, with a 2.2-fold elevation in risk; diabetes, with a 1.9-fold risk; and female sex, with an adjusted 1.75-fold increased risk (J Vasc Surg. 2016 Apr;63[4]:866-72).

Of note, these risk factors are largely unmodifiable, which underscores the importance of vigorous surveillance for possible signs of ischemic colitis during the first 4 days after AAA repair, especially in patients with multiple risk factors, Dr. Fujitani said.

Also, careful intraoperative assessment of the collateral mesenteric vascular anatomy is important in assessing a patient’s risk for postoperative ischemic colitis. This assessment should include the superior and inferior mesenteric arteries, as well as the celiac and internal iliac arteries. It’s worth bearing in mind that, even though collateral flow may appear adequate, it can be affected by hypovolemia, hypotension, or low cardiac output, the surgeon continued.

In the NSQIP data analysis, no patients who underwent reimplantation of the inferior mesenteric artery during open repair developed postoperative ischemic colitis. While this is an encouraging finding, the numbers were too small to draw definitive conclusions as to whether reimplantation of the artery is protective. It’s an important issue for further study, though, since so few of the recognized risk factors for the complication are modifiable, Dr. Fujitani noted.

He reported having no financial conflicts regarding his presentation.

 

bjancin@frontlinemedcom.com

 

EXPERT ANALYSIS FROM THE NORTHWESTERN VASCULAR SYMPOSIUM

CHICAGO – Postoperative ischemic colitis after abdominal aortic aneurysm (AAA) repair is a feared, potentially devastating complication with a mortality approaching 50%, but early diagnosis can mitigate that risk, Roy M. Fujitani, MD, said at a symposium on vascular surgery sponsored by Northwestern University in Chicago.

Bruce Jancin/Frontline Medical News

The key is to be familiar with the risk factors for this complication. Close surveillance of patients with multiple risk factors is particularly important for the first 4 days after AAA repair since more than three-quarters of cases are diagnosed in this time frame, according to Dr. Fujitani, professor and vice chair of surgery at University of California, Irvine.

The most common etiology of ischemic colitis following AAA repair is hypoperfusion of the mesenteric vasculature leading to nonocclusive ischemia. Caught early – in the initial hyperactive phase of colonic ischemia – the complication is typically transient and can be managed medically without further sequelae. Improvement is generally noted within a day or 2, with complete resolution within 1-2 weeks.

The earliest indicator that a patient is in the hyperactive phase of ischemic colitis following completion of an AAA repair can be defecation while still on the operating table.

“When you’ve just completed an operation and the patient has a bowel movement right on the operating table, that always makes me very, very concerned because of the likelihood of an associated ischemic colitis,” the surgeon noted.

A conscious patient in the first phase of ischemic colitis will describe an urgent desire to defecate, along with crampy pain and loose bowel movements with or without blood in the stool.

In the second, paralytic phase of ischemic colitis, the pain diminishes in intensity but becomes more continuous and diffuse, usually in the lateral borders of the abdomen. The abdomen becomes distended and much more tender, and there are no bowel sounds.

In patients whose ischemic colitis has been misdiagnosed or undiagnosed, the shock phase comes next. This is marked by massive fluid, protein, and electrolyte loss through the gangrenous mucosa. The result is severe dehydration, metabolic acidosis, and hypovolemic shock.

Nonocclusive colonic ischemia most often affects the watershed areas of the colon, such as the Sudeck point at the rectosigmoid junction.

The two other etiologies of ischemic colitis occurring as a complication of AAA repair are acute arterial occlusion, typically caused by iatrogenic embolization from a proximal source, often during endovascular aneurysm repair (EVAR), or rarely, venous thrombosis.
 

Making the diagnosis

When a patient is suspected of having ischemic colitis, one of the easiest ways of advancing toward a diagnosis is to obtain an abdominal plain x-ray, which classically shows thumb printing indicative of submucosal edema. CT with IV contrast typically shows bowel wall thickening, pericolonic fat stranding, and – most significantly – there may be free air within the colonic wall, an indicator of more advanced ischemia that occurs shortly before transmural gangrenous changes.

Colonoscopy is, however, the mainstay of diagnosis. It should be performed in any patient where postoperative ischemic colitis is suspected.
 

Ischemic colitis risk factors and outcomes

Dr. Fujitani was senior author of the largest ever study of risk factors for and outcomes of postoperative ischemic colitis in patients undergoing contemporary methods of open and endovascular AAA repair. This retrospective analysis of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database included 3,486 patients who underwent AAA repair in U.S. hospitals during 2011-2012. Twelve percent had an open repair, while the other 88% underwent EVAR.

The incidence of postoperative ischemic colitis was 2.2%. The median time of diagnosis was on postoperative day 2. The rate was nearly threefold higher in the open repair group: 5.2% versus 1.8%. However, the open-repair group had a higher rate of emergency admission, ruptured aneurysm before surgery, and other high-risk features. Upon multivariate analysis, the adjusted risk of postoperative ischemic colitis was no longer significantly different in the open-repair and EVAR groups.

The mean hospital length of stay in patients with postoperative ischemic colitis was 20 days, compared with 5 days in those without the complication. The unadjusted in-hospital mortality rate in patients with ischemic colitis was 39% versus 4% in those without ischemic colitis.

Of the 75 patients who developed postoperative ischemic colitis, 37 were managed medically, 38 surgically.

“What was quite surprising was that there was a 56.8% in-hospital mortality in the surgically treated patients. The point being that if you end up having ischemic colitis, there’s a 50% chance you’ll end up requiring an operation, and if you do undergo an operation you have more than a 50% chance of succumbing from the process,” Dr. Fujitani observed.

Dr. Fujitani and his coinvestigators scrutinized a plethora of potential risk factors for postoperative ischemic colitis. Six emerged as significant upon multivariate analysis: ruptured aneurysm before surgery, with an associated adjusted 4.1-fold increased risk; need for intra- or postoperative transfusion, with a 6-fold increased risk; renal failure requiring dialysis, with a 3.9-fold risk; proximal extension of the aneurysm, with a 2.2-fold elevation in risk; diabetes, with a 1.9-fold risk; and female sex, with an adjusted 1.75-fold increased risk (J Vasc Surg. 2016 Apr;63[4]:866-72).

Of note, these risk factors are largely unmodifiable, which underscores the importance of vigorous surveillance for possible signs of ischemic colitis during the first 4 days after AAA repair, especially in patients with multiple risk factors, Dr. Fujitani said.

Also, careful intraoperative assessment of the collateral mesenteric vascular anatomy is important in assessing a patient’s risk for postoperative ischemic colitis. This assessment should include the superior and inferior mesenteric arteries, as well as the celiac and internal iliac arteries. It’s worth bearing in mind that, even though collateral flow may appear adequate, it can be affected by hypovolemia, hypotension, or low cardiac output, the surgeon continued.

In the NSQIP data analysis, no patients who underwent reimplantation of the inferior mesenteric artery during open repair developed postoperative ischemic colitis. While this is an encouraging finding, the numbers were too small to draw definitive conclusions as to whether reimplantation of the artery is protective. It’s an important issue for further study, though, since so few of the recognized risk factors for the complication are modifiable, Dr. Fujitani noted.

He reported having no financial conflicts regarding his presentation.

 

bjancin@frontlinemedcom.com

 

EXPERT ANALYSIS FROM THE NORTHWESTERN VASCULAR SYMPOSIUM

CHICAGO – Postoperative ischemic colitis after abdominal aortic aneurysm (AAA) repair is a feared, potentially devastating complication with a mortality approaching 50%, but early diagnosis can mitigate that risk, Roy M. Fujitani, MD, said at a symposium on vascular surgery sponsored by Northwestern University in Chicago.

Bruce Jancin/Frontline Medical News

The key is to be familiar with the risk factors for this complication. Close surveillance of patients with multiple risk factors is particularly important for the first 4 days after AAA repair since more than three-quarters of cases are diagnosed in this time frame, according to Dr. Fujitani, professor and vice chair of surgery at University of California, Irvine.

The most common etiology of ischemic colitis following AAA repair is hypoperfusion of the mesenteric vasculature leading to nonocclusive ischemia. Caught early – in the initial hyperactive phase of colonic ischemia – the complication is typically transient and can be managed medically without further sequelae. Improvement is generally noted within a day or 2, with complete resolution within 1-2 weeks.

The earliest indicator that a patient is in the hyperactive phase of ischemic colitis following completion of an AAA repair can be defecation while still on the operating table.

“When you’ve just completed an operation and the patient has a bowel movement right on the operating table, that always makes me very, very concerned because of the likelihood of an associated ischemic colitis,” the surgeon noted.

A conscious patient in the first phase of ischemic colitis will describe an urgent desire to defecate, along with crampy pain and loose bowel movements with or without blood in the stool.

In the second, paralytic phase of ischemic colitis, the pain diminishes in intensity but becomes more continuous and diffuse, usually in the lateral borders of the abdomen. The abdomen becomes distended and much more tender, and there are no bowel sounds.

In patients whose ischemic colitis has been misdiagnosed or undiagnosed, the shock phase comes next. This is marked by massive fluid, protein, and electrolyte loss through the gangrenous mucosa. The result is severe dehydration, metabolic acidosis, and hypovolemic shock.

Nonocclusive colonic ischemia most often affects the watershed areas of the colon, such as the Sudeck point at the rectosigmoid junction.

The two other etiologies of ischemic colitis occurring as a complication of AAA repair are acute arterial occlusion, typically caused by iatrogenic embolization from a proximal source, often during endovascular aneurysm repair (EVAR), or rarely, venous thrombosis.
 

Making the diagnosis

When a patient is suspected of having ischemic colitis, one of the easiest ways of advancing toward a diagnosis is to obtain an abdominal plain x-ray, which classically shows thumb printing indicative of submucosal edema. CT with IV contrast typically shows bowel wall thickening, pericolonic fat stranding, and – most significantly – there may be free air within the colonic wall, an indicator of more advanced ischemia that occurs shortly before transmural gangrenous changes.

Colonoscopy is, however, the mainstay of diagnosis. It should be performed in any patient where postoperative ischemic colitis is suspected.
 

Ischemic colitis risk factors and outcomes

Dr. Fujitani was senior author of the largest ever study of risk factors for and outcomes of postoperative ischemic colitis in patients undergoing contemporary methods of open and endovascular AAA repair. This retrospective analysis of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database included 3,486 patients who underwent AAA repair in U.S. hospitals during 2011-2012. Twelve percent had an open repair, while the other 88% underwent EVAR.

The incidence of postoperative ischemic colitis was 2.2%. The median time of diagnosis was on postoperative day 2. The rate was nearly threefold higher in the open repair group: 5.2% versus 1.8%. However, the open-repair group had a higher rate of emergency admission, ruptured aneurysm before surgery, and other high-risk features. Upon multivariate analysis, the adjusted risk of postoperative ischemic colitis was no longer significantly different in the open-repair and EVAR groups.

The mean hospital length of stay in patients with postoperative ischemic colitis was 20 days, compared with 5 days in those without the complication. The unadjusted in-hospital mortality rate in patients with ischemic colitis was 39% versus 4% in those without ischemic colitis.

Of the 75 patients who developed postoperative ischemic colitis, 37 were managed medically, 38 surgically.

“What was quite surprising was that there was a 56.8% in-hospital mortality in the surgically treated patients. The point being that if you end up having ischemic colitis, there’s a 50% chance you’ll end up requiring an operation, and if you do undergo an operation you have more than a 50% chance of succumbing from the process,” Dr. Fujitani observed.

Dr. Fujitani and his coinvestigators scrutinized a plethora of potential risk factors for postoperative ischemic colitis. Six emerged as significant upon multivariate analysis: ruptured aneurysm before surgery, with an associated adjusted 4.1-fold increased risk; need for intra- or postoperative transfusion, with a 6-fold increased risk; renal failure requiring dialysis, with a 3.9-fold risk; proximal extension of the aneurysm, with a 2.2-fold elevation in risk; diabetes, with a 1.9-fold risk; and female sex, with an adjusted 1.75-fold increased risk (J Vasc Surg. 2016 Apr;63[4]:866-72).

Of note, these risk factors are largely unmodifiable, which underscores the importance of vigorous surveillance for possible signs of ischemic colitis during the first 4 days after AAA repair, especially in patients with multiple risk factors, Dr. Fujitani said.

Also, careful intraoperative assessment of the collateral mesenteric vascular anatomy is important in assessing a patient’s risk for postoperative ischemic colitis. This assessment should include the superior and inferior mesenteric arteries, as well as the celiac and internal iliac arteries. It’s worth bearing in mind that, even though collateral flow may appear adequate, it can be affected by hypovolemia, hypotension, or low cardiac output, the surgeon continued.

In the NSQIP data analysis, no patients who underwent reimplantation of the inferior mesenteric artery during open repair developed postoperative ischemic colitis. While this is an encouraging finding, the numbers were too small to draw definitive conclusions as to whether reimplantation of the artery is protective. It’s an important issue for further study, though, since so few of the recognized risk factors for the complication are modifiable, Dr. Fujitani noted.

He reported having no financial conflicts regarding his presentation.

 

bjancin@frontlinemedcom.com

 

ANAHEIM, CALIF. – Variability in fasting lipid levels over time in statin-treated patients is of prognostic importance, David D. Waters, MD, reported at the American Heart Association scientific sessions.

More specifically, above-average visit-to-visit variability in fasting triglycerides, LDL cholesterol, or HDL cholesterol in atorvastatin-treated patients with known coronary artery disease proved to be a strong and independent predictor of coronary and cardiovascular events in a post hoc analysis of the landmark Treating to New Targets (TNT) trial (N Engl J Med 2005;352:1425-35).

Bruce Jancin/Frontline Medical News

Also, high variability in triglyceride and LDL cholesterol levels – but not HDL cholesterol – independently predicted new-onset diabetes, added Dr. Waters, emeritus professor of medicine at the University of California, San Francisco.

The TNT trial randomized more than 10,000 subjects with known coronary artery disease and a baseline LDL cholesterol level below 130 mg/dL to receive either 10 or 80 mg/day of atorvastatin, with fasting lipids measured in a central laboratory at 3 and 12 months, then annually. The trial demonstrated that high-intensity statin therapy was more effective at preventing cardiovascular events than moderate-intensity therapy, thereby ushering in major changes in clinical practice guidelines.

The TNT investigators had previously reported that higher visit-to-visit variability in LDL cholesterol was independently associated with an increased rate of cardiovascular events during the median 4.9 years of study follow-up. In a multivariate regression analysis, each 1 standard deviation increase in average successive variability – that is, the average absolute difference between successive LDL cholesterol values – was associated with a 16% increase in the risk of any coronary event, an 11% increase in risk of any cardiovascular event, a 10% increase in MI, an 17% increase in stroke, and a 23% higher all-cause mortality independent of assignment treatment, achieved LDL cholesterol, demographics, and baseline cardiovascular risk factors.

At the AHA meeting in Anaheim, Dr. Waters presented an expanded analysis of 9,572 TNT participants that incorporated visit-to-visit variability in HDL cholesterol and triglycerides (J Am Coll Cardiol. 2015 Apr 21;65[15]:1539-48). Patients with 1 standard deviation of average successive variability (ASV) in triglycerides – that is, more than 30 mg/dL of visit-to-visit variability – had a 9% increased risk of coronary events during follow-up in a multivariate analysis. Patients with more than 4 mg/dL of variability in HDL cholesterol had a 16% increased risk compared with those with lesser variability.

“For both coronary and cardiovascular events, most of the increased risk appears to reside in the uppermost quintile,” the cardiologist observed.

Indeed, when the investigators divided patients into quintiles of ASV, the top quintile in terms of triglyceride variability had a 34% greater risk of coronary events, a 31% increase in risk of cardiovascular events, a 63% increase in stroke, a 65% increase in nonfatal MI, and a 92% greater likelihood of new-onset diabetes compared with patients in the lowest quintile of ASV. In contrast, these risks were not significantly elevated in the second, third, and fourth quintiles.

Similarly, patients in the top quintile for HDL cholesterol ASV had a 50% greater rate of coronary events, a 56% increased risk of cardiovascular events, a 70% increase in stroke, and a 61% increase in nonfatal MI, compared with those in the lowest quintile. Again, risks weren’t significantly increased in the second through fourth quintiles. Unlike with triglycerides, greater variability in fasting HDL cholesterol over time wasn’t predictive of new-onset diabetes.

Observers noted that these findings could be clinically relevant for patients who remain at high residual risk for atherosclerotic cardiovascular events even after aggressive LDL cholesterol lowering.

Variability in levels of the three lipids was only weakly correlated.

Dr. Waters made a plea to his audience, “The mechanisms accounting for these associations are unknown. If you can suggest for me any possibility of what the causes are, I’d be very happy to hear it and go back to try to verify it.”

He reported serving as a consultant to Resverlogix, CSL Limited, the Medicines Company, Pfizer, and Sanofi-Aventis.
 

bjancin@frontlinemedcom.com

 

ANAHEIM, CALIF. – Variability in fasting lipid levels over time in statin-treated patients is of prognostic importance, David D. Waters, MD, reported at the American Heart Association scientific sessions.

More specifically, above-average visit-to-visit variability in fasting triglycerides, LDL cholesterol, or HDL cholesterol in atorvastatin-treated patients with known coronary artery disease proved to be a strong and independent predictor of coronary and cardiovascular events in a post hoc analysis of the landmark Treating to New Targets (TNT) trial (N Engl J Med 2005;352:1425-35).

Bruce Jancin/Frontline Medical News

Also, high variability in triglyceride and LDL cholesterol levels – but not HDL cholesterol – independently predicted new-onset diabetes, added Dr. Waters, emeritus professor of medicine at the University of California, San Francisco.

The TNT trial randomized more than 10,000 subjects with known coronary artery disease and a baseline LDL cholesterol level below 130 mg/dL to receive either 10 or 80 mg/day of atorvastatin, with fasting lipids measured in a central laboratory at 3 and 12 months, then annually. The trial demonstrated that high-intensity statin therapy was more effective at preventing cardiovascular events than moderate-intensity therapy, thereby ushering in major changes in clinical practice guidelines.

The TNT investigators had previously reported that higher visit-to-visit variability in LDL cholesterol was independently associated with an increased rate of cardiovascular events during the median 4.9 years of study follow-up. In a multivariate regression analysis, each 1 standard deviation increase in average successive variability – that is, the average absolute difference between successive LDL cholesterol values – was associated with a 16% increase in the risk of any coronary event, an 11% increase in risk of any cardiovascular event, a 10% increase in MI, an 17% increase in stroke, and a 23% higher all-cause mortality independent of assignment treatment, achieved LDL cholesterol, demographics, and baseline cardiovascular risk factors.

At the AHA meeting in Anaheim, Dr. Waters presented an expanded analysis of 9,572 TNT participants that incorporated visit-to-visit variability in HDL cholesterol and triglycerides (J Am Coll Cardiol. 2015 Apr 21;65[15]:1539-48). Patients with 1 standard deviation of average successive variability (ASV) in triglycerides – that is, more than 30 mg/dL of visit-to-visit variability – had a 9% increased risk of coronary events during follow-up in a multivariate analysis. Patients with more than 4 mg/dL of variability in HDL cholesterol had a 16% increased risk compared with those with lesser variability.

“For both coronary and cardiovascular events, most of the increased risk appears to reside in the uppermost quintile,” the cardiologist observed.

Indeed, when the investigators divided patients into quintiles of ASV, the top quintile in terms of triglyceride variability had a 34% greater risk of coronary events, a 31% increase in risk of cardiovascular events, a 63% increase in stroke, a 65% increase in nonfatal MI, and a 92% greater likelihood of new-onset diabetes compared with patients in the lowest quintile of ASV. In contrast, these risks were not significantly elevated in the second, third, and fourth quintiles.

Similarly, patients in the top quintile for HDL cholesterol ASV had a 50% greater rate of coronary events, a 56% increased risk of cardiovascular events, a 70% increase in stroke, and a 61% increase in nonfatal MI, compared with those in the lowest quintile. Again, risks weren’t significantly increased in the second through fourth quintiles. Unlike with triglycerides, greater variability in fasting HDL cholesterol over time wasn’t predictive of new-onset diabetes.

Observers noted that these findings could be clinically relevant for patients who remain at high residual risk for atherosclerotic cardiovascular events even after aggressive LDL cholesterol lowering.

Variability in levels of the three lipids was only weakly correlated.

Dr. Waters made a plea to his audience, “The mechanisms accounting for these associations are unknown. If you can suggest for me any possibility of what the causes are, I’d be very happy to hear it and go back to try to verify it.”

He reported serving as a consultant to Resverlogix, CSL Limited, the Medicines Company, Pfizer, and Sanofi-Aventis.
 

bjancin@frontlinemedcom.com

 

ANAHEIM, CALIF. – Variability in fasting lipid levels over time in statin-treated patients is of prognostic importance, David D. Waters, MD, reported at the American Heart Association scientific sessions.

More specifically, above-average visit-to-visit variability in fasting triglycerides, LDL cholesterol, or HDL cholesterol in atorvastatin-treated patients with known coronary artery disease proved to be a strong and independent predictor of coronary and cardiovascular events in a post hoc analysis of the landmark Treating to New Targets (TNT) trial (N Engl J Med 2005;352:1425-35).

Bruce Jancin/Frontline Medical News

Also, high variability in triglyceride and LDL cholesterol levels – but not HDL cholesterol – independently predicted new-onset diabetes, added Dr. Waters, emeritus professor of medicine at the University of California, San Francisco.

The TNT trial randomized more than 10,000 subjects with known coronary artery disease and a baseline LDL cholesterol level below 130 mg/dL to receive either 10 or 80 mg/day of atorvastatin, with fasting lipids measured in a central laboratory at 3 and 12 months, then annually. The trial demonstrated that high-intensity statin therapy was more effective at preventing cardiovascular events than moderate-intensity therapy, thereby ushering in major changes in clinical practice guidelines.

The TNT investigators had previously reported that higher visit-to-visit variability in LDL cholesterol was independently associated with an increased rate of cardiovascular events during the median 4.9 years of study follow-up. In a multivariate regression analysis, each 1 standard deviation increase in average successive variability – that is, the average absolute difference between successive LDL cholesterol values – was associated with a 16% increase in the risk of any coronary event, an 11% increase in risk of any cardiovascular event, a 10% increase in MI, an 17% increase in stroke, and a 23% higher all-cause mortality independent of assignment treatment, achieved LDL cholesterol, demographics, and baseline cardiovascular risk factors.

At the AHA meeting in Anaheim, Dr. Waters presented an expanded analysis of 9,572 TNT participants that incorporated visit-to-visit variability in HDL cholesterol and triglycerides (J Am Coll Cardiol. 2015 Apr 21;65[15]:1539-48). Patients with 1 standard deviation of average successive variability (ASV) in triglycerides – that is, more than 30 mg/dL of visit-to-visit variability – had a 9% increased risk of coronary events during follow-up in a multivariate analysis. Patients with more than 4 mg/dL of variability in HDL cholesterol had a 16% increased risk compared with those with lesser variability.

“For both coronary and cardiovascular events, most of the increased risk appears to reside in the uppermost quintile,” the cardiologist observed.

Indeed, when the investigators divided patients into quintiles of ASV, the top quintile in terms of triglyceride variability had a 34% greater risk of coronary events, a 31% increase in risk of cardiovascular events, a 63% increase in stroke, a 65% increase in nonfatal MI, and a 92% greater likelihood of new-onset diabetes compared with patients in the lowest quintile of ASV. In contrast, these risks were not significantly elevated in the second, third, and fourth quintiles.

Similarly, patients in the top quintile for HDL cholesterol ASV had a 50% greater rate of coronary events, a 56% increased risk of cardiovascular events, a 70% increase in stroke, and a 61% increase in nonfatal MI, compared with those in the lowest quintile. Again, risks weren’t significantly increased in the second through fourth quintiles. Unlike with triglycerides, greater variability in fasting HDL cholesterol over time wasn’t predictive of new-onset diabetes.

Observers noted that these findings could be clinically relevant for patients who remain at high residual risk for atherosclerotic cardiovascular events even after aggressive LDL cholesterol lowering.

Variability in levels of the three lipids was only weakly correlated.

Dr. Waters made a plea to his audience, “The mechanisms accounting for these associations are unknown. If you can suggest for me any possibility of what the causes are, I’d be very happy to hear it and go back to try to verify it.”

He reported serving as a consultant to Resverlogix, CSL Limited, the Medicines Company, Pfizer, and Sanofi-Aventis.
 

bjancin@frontlinemedcom.com

 

SNOWMASS, COLO. – One of the toughest tasks in all of preventive cardiology is to convince statin-phobic patients at increased cardiovascular risk that they should take a statin, Robert A. Vogel, MD, observed.

“The two hardest challenges I have in my practice are getting people to stop smoking and getting people who have fear of statins to take statins. That’s half my practice. If I could conquer those two goals it would be like climbing Mount Everest,” declared Dr. Vogel, a cardiologist at the University of Colorado, Denver.

Bruce Jancin/Frontline Medical News

In his talk, he tackled the various safety concerns about statins that have been raised over the years, including statin-induced cognitive decline, myalgias, new-onset diabetes, hepatic dysfunction, and hemorrhagic stroke. Some of these concerns have turned out to be meritless, others are real but often widely overblown on irresponsible Internet sites frequented by patients. And then there is hemorrhagic stroke.

“There is one true harm of a statin that I always worry about, and that’s hemorrhagic stroke. It’s rare, but it does occur,” the cardiologist said at the Annual Cardiovascular Conference at Snowmass.

Dr. Vogel highlighted key studies that he believes have convincingly addressed impaired cognition and other proposed statin side effects. He also provided an update on the safety profile of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.

Neurocognitive problems: The Food and Drug Administration really ratcheted up patient fretting when it mandated in 2012 that the labeling for all statins must include a warning of postmarketing reports of adverse events involving ill-defined memory impairment and confusion that were reversed upon drug discontinuation.

“I can tell you, I’ve had dozens of patients come in and say, ‘What about this warning? I’m afraid of dementia,’ ” Dr. Vogel said.

It’s tough to refute anecdotal case reports, but Dr. Vogel pointed to several published meta-analyses of prospective cohort studies, randomized controlled trials, and cross-sectional studies to illustrate his point. For example, investigators at Johns Hopkins University in Baltimore analyzed the results of 16 high-quality randomized trials and prospective cohort studies and found that the short-term studies showed no effect of statin therapy on measurable cognitive endpoints. Moreover, the pooled results of eight long-term studies, including more than 23,000 patients, showed a significant 29% reduction in new-onset dementia in statin-treated patients (Mayo Clin Proc. 2013 Nov;88[11]1213-21).

Another meta-analysis, this one including 27 studies, concluded there is “moderate-quality evidence” to suggest statin users have no increased incidence of dementia, mild cognitive impairment, or any change in neurocognitive scores related to executive function, declarative memory, processing speed, or global cognitive performance.

In this same report, the investigators delved into the FDA’s adverse event reporting database and determined that the rate of reported cognitive-related adverse events was 1.9 cases per 1 million statin prescriptions, identical to the rate for clopidogrel and essentially the same as the 1.6 cases per 1 million rate for losartan (Ann Intern Med. 2013 Nov 19;159[10]:688-97).

“It shows that if you take any drug and put it in the type of population we give these drugs to, you’re going to see about the same frequency of these anecdotal reports, with no signal that statins are any worse than any other drugs we use in cardiology. Is this proof that statins don’t cause cognitive impairment? No, but it’s suggestive that if you give drugs, people have adverse events that may or may not be related to those drugs. So this was reassuring to me that we’ll see this stuff anecdotally, but it probably isn’t due to the statin itself,” Dr. Vogel continued.

Myalgia: In the STOMP study (Effect of Statins on Skeletal Muscle Function and Performance), investigators at Hartford (Conn.) Hospital randomized 420 healthy, statin-naive subjects in a double-blind fashion to 80 mg/day of atorvastatin or placebo for 6 months. The incidence of myalgia was 9.4% in the atorvastatin group compared with 4.6% in placebo-treated controls. Of note, muscle strength on formal testing wasn’t reduced to a greater extent in myalgic patients on atorvastatin than in myalgic patients on placebo (Circulation. 2013 Jan 1;127[1]:96-103).

“There is a signal there,” Dr. Vogel commented. “So the true [placebo-subtracted] incidence of myalgias on a high-dose statin is about 5%. It’s not 20%, it’s not 30%, it’s about 1 patient in 20. It’s real, but it’s not everybody. Those are the numbers you have to think about. If half your patients on statin therapy are getting myalgias, you need to go into a different practice because you’ve got a bunch of Web-searching patients.”

Diabetes: A meta-analysis of 13 randomized controlled trials of statins with more than 91,000 participants and a mean of 4 years of follow-up concluded that for every 255 patients treated with a statin for 4 years, there would be one extra case of new-onset type 2 diabetes, a harm dwarfed by the reduction in cardiovascular events (Lancet. 2010 Feb 27;375[9716]:735-42).

The mechanism for this statin-related, slightly increased risk of developing type 2 diabetes has been clarified by a genetic analysis involving more than 223,000 participants in 43 genetic studies. A large multicenter team of investigators showed that genetic polymorphisms resulting in a less active 3-hydroxy-3-methylglutaryl-coenzyme A reductase gene are associated with lower LDL cholesterol, slightly higher body weight and waist circumference, and increased plasma insulin and plasma glucose. The investigators showed that the more of these alleles an individual possessed, the greater the risk of type 2 diabetes (Lancet. 2015 Jan 24;385[9965]:351-61).

Hemorrhagic stroke: In the SPARCL study (Stroke Prevention by Aggressive Reduction in Cholesterol Levels), 4,731 patients with a recent stroke or transient ischemic attack – 67% of which were ischemic strokes, 2% hemorrhagic strokes – were randomized to high-dose atorvastatin or placebo. Atorvastatin for secondary prevention markedly reduced the overall stroke risk. But this was due to a dramatic decrease in ischemic strokes. The incidence of hemorrhagic stroke was 2.3% in patients on atorvastatin at 80 mg/day for secondary prevention, compared with 1.4% in placebo-treated controls.

In multivariate analysis, the SPARCL investigators found that hemorrhagic stroke risk was increased by an adjusted 68% in patients on atorvastatin, 465% in patients whose prior stroke was hemorrhagic, and 519% in patients with a blood pressure reading of 160-179/100-109 mm Hg at their last clinic visit prior to the hemorrhagic stroke (Neurology. 2008 Jun 10;70[24 Pt 2]:2364-70).

Hepatic dysfunction: This event is extremely rare, so much so that it’s not listed as a side effect in statin labeling. Monitoring of liver function tests is no longer recommended in patients on statin therapy. If elevated tests are seen, find out about the patient’s alcohol consumption – the explanation is far more likely to lie there, according to Dr. Vogel.

 

What about the safety of the PCSK9 inhibitors?

Dr. Vogel is the U.S. national coordinator for the ongoing phase 3 ODYSSEY Outcomes Study, which is due to report initial results at the 2018 annual meeting of the American College of Cardiology. So far, albeit with only a couple of years worth of data in the large randomized outcome trials, the PCSK9 inhibitors haven’t been associated with muscle problems, cognitive impairment, hepatic dysfunction, or hemorrhagic stroke.

“I think we will eventually see an increased risk of hemorrhagic stroke. I don’t know why we wouldn’t because the mechanism is an antiplatelet mechanism, as with statins. But I don’t know what the incidence will be,” he said.

The EBBINGHAUS substudy of the ongoing FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) of the PCSK9 inhibitor evolocumab(Repatha) provides welcome data on cognition. EBBINGHAUS included 1,974 patients with atherosclerotic cardiovascular disease and normal cognition at baseline who underwent serial testing using the Cambridge Neuropsychological Test Automated Battery over the course of 2 years of prospective follow-up. No signal was seen of any impairment in spatial working memory, learning ability, or the elements of executive function, including planning, organization, and attention. Nor did structured assessment of patient self-reported everyday cognition differ between the active treatment and control arms. Ditto for investigators’ assessment of cognitive adverse events. Moreover, when it did occur, measurable cognitive decline proved unrelated to achieved LDL cholesterol level.

“Two-year data is not 20-year data. And cognitive decline is of great concern. Those of us in this field are going to remain vigilant and look for this, but at least for the present, when you put a patient on a PCSK9 inhibitor and see an LDL drop to 15 or 10 mg/dL – and you will see that happen – the data so far say we do not see cognitive decline,” Dr. Vogel said.

He reported serving as a paid consultant to the National Football League and receiving a research grant from and serving on the speakers bureau for Sanofi.

bjancin@frontlinemedcom.com

 

SNOWMASS, COLO. – One of the toughest tasks in all of preventive cardiology is to convince statin-phobic patients at increased cardiovascular risk that they should take a statin, Robert A. Vogel, MD, observed.

“The two hardest challenges I have in my practice are getting people to stop smoking and getting people who have fear of statins to take statins. That’s half my practice. If I could conquer those two goals it would be like climbing Mount Everest,” declared Dr. Vogel, a cardiologist at the University of Colorado, Denver.

Bruce Jancin/Frontline Medical News

In his talk, he tackled the various safety concerns about statins that have been raised over the years, including statin-induced cognitive decline, myalgias, new-onset diabetes, hepatic dysfunction, and hemorrhagic stroke. Some of these concerns have turned out to be meritless, others are real but often widely overblown on irresponsible Internet sites frequented by patients. And then there is hemorrhagic stroke.

“There is one true harm of a statin that I always worry about, and that’s hemorrhagic stroke. It’s rare, but it does occur,” the cardiologist said at the Annual Cardiovascular Conference at Snowmass.

Dr. Vogel highlighted key studies that he believes have convincingly addressed impaired cognition and other proposed statin side effects. He also provided an update on the safety profile of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.

Neurocognitive problems: The Food and Drug Administration really ratcheted up patient fretting when it mandated in 2012 that the labeling for all statins must include a warning of postmarketing reports of adverse events involving ill-defined memory impairment and confusion that were reversed upon drug discontinuation.

“I can tell you, I’ve had dozens of patients come in and say, ‘What about this warning? I’m afraid of dementia,’ ” Dr. Vogel said.

It’s tough to refute anecdotal case reports, but Dr. Vogel pointed to several published meta-analyses of prospective cohort studies, randomized controlled trials, and cross-sectional studies to illustrate his point. For example, investigators at Johns Hopkins University in Baltimore analyzed the results of 16 high-quality randomized trials and prospective cohort studies and found that the short-term studies showed no effect of statin therapy on measurable cognitive endpoints. Moreover, the pooled results of eight long-term studies, including more than 23,000 patients, showed a significant 29% reduction in new-onset dementia in statin-treated patients (Mayo Clin Proc. 2013 Nov;88[11]1213-21).

Another meta-analysis, this one including 27 studies, concluded there is “moderate-quality evidence” to suggest statin users have no increased incidence of dementia, mild cognitive impairment, or any change in neurocognitive scores related to executive function, declarative memory, processing speed, or global cognitive performance.

In this same report, the investigators delved into the FDA’s adverse event reporting database and determined that the rate of reported cognitive-related adverse events was 1.9 cases per 1 million statin prescriptions, identical to the rate for clopidogrel and essentially the same as the 1.6 cases per 1 million rate for losartan (Ann Intern Med. 2013 Nov 19;159[10]:688-97).

“It shows that if you take any drug and put it in the type of population we give these drugs to, you’re going to see about the same frequency of these anecdotal reports, with no signal that statins are any worse than any other drugs we use in cardiology. Is this proof that statins don’t cause cognitive impairment? No, but it’s suggestive that if you give drugs, people have adverse events that may or may not be related to those drugs. So this was reassuring to me that we’ll see this stuff anecdotally, but it probably isn’t due to the statin itself,” Dr. Vogel continued.

Myalgia: In the STOMP study (Effect of Statins on Skeletal Muscle Function and Performance), investigators at Hartford (Conn.) Hospital randomized 420 healthy, statin-naive subjects in a double-blind fashion to 80 mg/day of atorvastatin or placebo for 6 months. The incidence of myalgia was 9.4% in the atorvastatin group compared with 4.6% in placebo-treated controls. Of note, muscle strength on formal testing wasn’t reduced to a greater extent in myalgic patients on atorvastatin than in myalgic patients on placebo (Circulation. 2013 Jan 1;127[1]:96-103).

“There is a signal there,” Dr. Vogel commented. “So the true [placebo-subtracted] incidence of myalgias on a high-dose statin is about 5%. It’s not 20%, it’s not 30%, it’s about 1 patient in 20. It’s real, but it’s not everybody. Those are the numbers you have to think about. If half your patients on statin therapy are getting myalgias, you need to go into a different practice because you’ve got a bunch of Web-searching patients.”

Diabetes: A meta-analysis of 13 randomized controlled trials of statins with more than 91,000 participants and a mean of 4 years of follow-up concluded that for every 255 patients treated with a statin for 4 years, there would be one extra case of new-onset type 2 diabetes, a harm dwarfed by the reduction in cardiovascular events (Lancet. 2010 Feb 27;375[9716]:735-42).

The mechanism for this statin-related, slightly increased risk of developing type 2 diabetes has been clarified by a genetic analysis involving more than 223,000 participants in 43 genetic studies. A large multicenter team of investigators showed that genetic polymorphisms resulting in a less active 3-hydroxy-3-methylglutaryl-coenzyme A reductase gene are associated with lower LDL cholesterol, slightly higher body weight and waist circumference, and increased plasma insulin and plasma glucose. The investigators showed that the more of these alleles an individual possessed, the greater the risk of type 2 diabetes (Lancet. 2015 Jan 24;385[9965]:351-61).

Hemorrhagic stroke: In the SPARCL study (Stroke Prevention by Aggressive Reduction in Cholesterol Levels), 4,731 patients with a recent stroke or transient ischemic attack – 67% of which were ischemic strokes, 2% hemorrhagic strokes – were randomized to high-dose atorvastatin or placebo. Atorvastatin for secondary prevention markedly reduced the overall stroke risk. But this was due to a dramatic decrease in ischemic strokes. The incidence of hemorrhagic stroke was 2.3% in patients on atorvastatin at 80 mg/day for secondary prevention, compared with 1.4% in placebo-treated controls.

In multivariate analysis, the SPARCL investigators found that hemorrhagic stroke risk was increased by an adjusted 68% in patients on atorvastatin, 465% in patients whose prior stroke was hemorrhagic, and 519% in patients with a blood pressure reading of 160-179/100-109 mm Hg at their last clinic visit prior to the hemorrhagic stroke (Neurology. 2008 Jun 10;70[24 Pt 2]:2364-70).

Hepatic dysfunction: This event is extremely rare, so much so that it’s not listed as a side effect in statin labeling. Monitoring of liver function tests is no longer recommended in patients on statin therapy. If elevated tests are seen, find out about the patient’s alcohol consumption – the explanation is far more likely to lie there, according to Dr. Vogel.

 

What about the safety of the PCSK9 inhibitors?

Dr. Vogel is the U.S. national coordinator for the ongoing phase 3 ODYSSEY Outcomes Study, which is due to report initial results at the 2018 annual meeting of the American College of Cardiology. So far, albeit with only a couple of years worth of data in the large randomized outcome trials, the PCSK9 inhibitors haven’t been associated with muscle problems, cognitive impairment, hepatic dysfunction, or hemorrhagic stroke.

“I think we will eventually see an increased risk of hemorrhagic stroke. I don’t know why we wouldn’t because the mechanism is an antiplatelet mechanism, as with statins. But I don’t know what the incidence will be,” he said.

The EBBINGHAUS substudy of the ongoing FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) of the PCSK9 inhibitor evolocumab(Repatha) provides welcome data on cognition. EBBINGHAUS included 1,974 patients with atherosclerotic cardiovascular disease and normal cognition at baseline who underwent serial testing using the Cambridge Neuropsychological Test Automated Battery over the course of 2 years of prospective follow-up. No signal was seen of any impairment in spatial working memory, learning ability, or the elements of executive function, including planning, organization, and attention. Nor did structured assessment of patient self-reported everyday cognition differ between the active treatment and control arms. Ditto for investigators’ assessment of cognitive adverse events. Moreover, when it did occur, measurable cognitive decline proved unrelated to achieved LDL cholesterol level.

“Two-year data is not 20-year data. And cognitive decline is of great concern. Those of us in this field are going to remain vigilant and look for this, but at least for the present, when you put a patient on a PCSK9 inhibitor and see an LDL drop to 15 or 10 mg/dL – and you will see that happen – the data so far say we do not see cognitive decline,” Dr. Vogel said.

He reported serving as a paid consultant to the National Football League and receiving a research grant from and serving on the speakers bureau for Sanofi.

bjancin@frontlinemedcom.com

 

SNOWMASS, COLO. – One of the toughest tasks in all of preventive cardiology is to convince statin-phobic patients at increased cardiovascular risk that they should take a statin, Robert A. Vogel, MD, observed.

“The two hardest challenges I have in my practice are getting people to stop smoking and getting people who have fear of statins to take statins. That’s half my practice. If I could conquer those two goals it would be like climbing Mount Everest,” declared Dr. Vogel, a cardiologist at the University of Colorado, Denver.

Bruce Jancin/Frontline Medical News

In his talk, he tackled the various safety concerns about statins that have been raised over the years, including statin-induced cognitive decline, myalgias, new-onset diabetes, hepatic dysfunction, and hemorrhagic stroke. Some of these concerns have turned out to be meritless, others are real but often widely overblown on irresponsible Internet sites frequented by patients. And then there is hemorrhagic stroke.

“There is one true harm of a statin that I always worry about, and that’s hemorrhagic stroke. It’s rare, but it does occur,” the cardiologist said at the Annual Cardiovascular Conference at Snowmass.

Dr. Vogel highlighted key studies that he believes have convincingly addressed impaired cognition and other proposed statin side effects. He also provided an update on the safety profile of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.

Neurocognitive problems: The Food and Drug Administration really ratcheted up patient fretting when it mandated in 2012 that the labeling for all statins must include a warning of postmarketing reports of adverse events involving ill-defined memory impairment and confusion that were reversed upon drug discontinuation.

“I can tell you, I’ve had dozens of patients come in and say, ‘What about this warning? I’m afraid of dementia,’ ” Dr. Vogel said.

It’s tough to refute anecdotal case reports, but Dr. Vogel pointed to several published meta-analyses of prospective cohort studies, randomized controlled trials, and cross-sectional studies to illustrate his point. For example, investigators at Johns Hopkins University in Baltimore analyzed the results of 16 high-quality randomized trials and prospective cohort studies and found that the short-term studies showed no effect of statin therapy on measurable cognitive endpoints. Moreover, the pooled results of eight long-term studies, including more than 23,000 patients, showed a significant 29% reduction in new-onset dementia in statin-treated patients (Mayo Clin Proc. 2013 Nov;88[11]1213-21).

Another meta-analysis, this one including 27 studies, concluded there is “moderate-quality evidence” to suggest statin users have no increased incidence of dementia, mild cognitive impairment, or any change in neurocognitive scores related to executive function, declarative memory, processing speed, or global cognitive performance.

In this same report, the investigators delved into the FDA’s adverse event reporting database and determined that the rate of reported cognitive-related adverse events was 1.9 cases per 1 million statin prescriptions, identical to the rate for clopidogrel and essentially the same as the 1.6 cases per 1 million rate for losartan (Ann Intern Med. 2013 Nov 19;159[10]:688-97).

“It shows that if you take any drug and put it in the type of population we give these drugs to, you’re going to see about the same frequency of these anecdotal reports, with no signal that statins are any worse than any other drugs we use in cardiology. Is this proof that statins don’t cause cognitive impairment? No, but it’s suggestive that if you give drugs, people have adverse events that may or may not be related to those drugs. So this was reassuring to me that we’ll see this stuff anecdotally, but it probably isn’t due to the statin itself,” Dr. Vogel continued.

Myalgia: In the STOMP study (Effect of Statins on Skeletal Muscle Function and Performance), investigators at Hartford (Conn.) Hospital randomized 420 healthy, statin-naive subjects in a double-blind fashion to 80 mg/day of atorvastatin or placebo for 6 months. The incidence of myalgia was 9.4% in the atorvastatin group compared with 4.6% in placebo-treated controls. Of note, muscle strength on formal testing wasn’t reduced to a greater extent in myalgic patients on atorvastatin than in myalgic patients on placebo (Circulation. 2013 Jan 1;127[1]:96-103).

“There is a signal there,” Dr. Vogel commented. “So the true [placebo-subtracted] incidence of myalgias on a high-dose statin is about 5%. It’s not 20%, it’s not 30%, it’s about 1 patient in 20. It’s real, but it’s not everybody. Those are the numbers you have to think about. If half your patients on statin therapy are getting myalgias, you need to go into a different practice because you’ve got a bunch of Web-searching patients.”

Diabetes: A meta-analysis of 13 randomized controlled trials of statins with more than 91,000 participants and a mean of 4 years of follow-up concluded that for every 255 patients treated with a statin for 4 years, there would be one extra case of new-onset type 2 diabetes, a harm dwarfed by the reduction in cardiovascular events (Lancet. 2010 Feb 27;375[9716]:735-42).

The mechanism for this statin-related, slightly increased risk of developing type 2 diabetes has been clarified by a genetic analysis involving more than 223,000 participants in 43 genetic studies. A large multicenter team of investigators showed that genetic polymorphisms resulting in a less active 3-hydroxy-3-methylglutaryl-coenzyme A reductase gene are associated with lower LDL cholesterol, slightly higher body weight and waist circumference, and increased plasma insulin and plasma glucose. The investigators showed that the more of these alleles an individual possessed, the greater the risk of type 2 diabetes (Lancet. 2015 Jan 24;385[9965]:351-61).

Hemorrhagic stroke: In the SPARCL study (Stroke Prevention by Aggressive Reduction in Cholesterol Levels), 4,731 patients with a recent stroke or transient ischemic attack – 67% of which were ischemic strokes, 2% hemorrhagic strokes – were randomized to high-dose atorvastatin or placebo. Atorvastatin for secondary prevention markedly reduced the overall stroke risk. But this was due to a dramatic decrease in ischemic strokes. The incidence of hemorrhagic stroke was 2.3% in patients on atorvastatin at 80 mg/day for secondary prevention, compared with 1.4% in placebo-treated controls.

In multivariate analysis, the SPARCL investigators found that hemorrhagic stroke risk was increased by an adjusted 68% in patients on atorvastatin, 465% in patients whose prior stroke was hemorrhagic, and 519% in patients with a blood pressure reading of 160-179/100-109 mm Hg at their last clinic visit prior to the hemorrhagic stroke (Neurology. 2008 Jun 10;70[24 Pt 2]:2364-70).

Hepatic dysfunction: This event is extremely rare, so much so that it’s not listed as a side effect in statin labeling. Monitoring of liver function tests is no longer recommended in patients on statin therapy. If elevated tests are seen, find out about the patient’s alcohol consumption – the explanation is far more likely to lie there, according to Dr. Vogel.

 

What about the safety of the PCSK9 inhibitors?

Dr. Vogel is the U.S. national coordinator for the ongoing phase 3 ODYSSEY Outcomes Study, which is due to report initial results at the 2018 annual meeting of the American College of Cardiology. So far, albeit with only a couple of years worth of data in the large randomized outcome trials, the PCSK9 inhibitors haven’t been associated with muscle problems, cognitive impairment, hepatic dysfunction, or hemorrhagic stroke.

“I think we will eventually see an increased risk of hemorrhagic stroke. I don’t know why we wouldn’t because the mechanism is an antiplatelet mechanism, as with statins. But I don’t know what the incidence will be,” he said.

The EBBINGHAUS substudy of the ongoing FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) of the PCSK9 inhibitor evolocumab(Repatha) provides welcome data on cognition. EBBINGHAUS included 1,974 patients with atherosclerotic cardiovascular disease and normal cognition at baseline who underwent serial testing using the Cambridge Neuropsychological Test Automated Battery over the course of 2 years of prospective follow-up. No signal was seen of any impairment in spatial working memory, learning ability, or the elements of executive function, including planning, organization, and attention. Nor did structured assessment of patient self-reported everyday cognition differ between the active treatment and control arms. Ditto for investigators’ assessment of cognitive adverse events. Moreover, when it did occur, measurable cognitive decline proved unrelated to achieved LDL cholesterol level.

“Two-year data is not 20-year data. And cognitive decline is of great concern. Those of us in this field are going to remain vigilant and look for this, but at least for the present, when you put a patient on a PCSK9 inhibitor and see an LDL drop to 15 or 10 mg/dL – and you will see that happen – the data so far say we do not see cognitive decline,” Dr. Vogel said.

He reported serving as a paid consultant to the National Football League and receiving a research grant from and serving on the speakers bureau for Sanofi.

bjancin@frontlinemedcom.com

 

CHICAGO – The use of therapeutic-dose anticoagulation in hospitalized patients with calf vein thrombosis significantly reduces the risk of venous thromboembolic complications, compared with lower-dose prophylactic anticoagulation or surveillance alone, Heron E. Rodriguez, MD, said at a symposium on vascular surgery sponsored by Northwestern University.

Moreover, placement of an inferior vena cava filter in patients with calf vein thrombosis when anticoagulation is contraindicated accomplishes nothing beneficial and had a 10% complication rate in a large retrospective single-center study, added Dr. Rodriguez of Northwestern University, Chicago.

Bruce Jancin/Frontline Medical News

“In our population – patients that are in the hospital with risk factors for venous thromboembolic complications – we think that anticoagulation is a good idea. Low-risk patients or patients in whom anticoagulation is contraindicated should not be getting a filter. There’s really not any advantage in putting in a filter,” the vascular surgeon said.

Deep vein thrombosis (DVT) remains a significant source of morbidity and mortality despite worldwide awareness of the problem.

“Specifically, calf vein thrombosis [CVT] is very common, and we know that in some series up to 30% of patients end up propagating proximally if they’re not treated, and a good number of them develop chronic venous insufficiency, with long-term consequences,” he noted.

“Unfortunately there is no consensus regarding treatment. The guidelines are very vague. For example, there is no mention [in current American College of Chest Physicians guidelines] of how to manage muscular vein thrombosis and much ambiguity on how to treat calf vein thrombosis,” he continued.

Dr. Rodriguez cited as an indication of the lack of consensus on management of CVT a single-institution survey by other investigators of the practices of physicians in various specialties. Forty-nine percent of respondents indicated they anticoagulate patients with CVT; 51% don’t. Of those who did, 62% prescribed low-molecular-weight heparin and 11% intravenous heparin. Fifty-eight percent of physicians who anticoagulated did so for 3 months, 30% for 6. And 46% of physicians used an inferior vena cava (IVC) filter when anticoagulation was contraindicated (Vascular. 2014 Apr;22[2]:93-7).

That rate of IVC placement “seemed really high” given the paucity of supporting evidence for safety and efficacy of filter placement in the setting of CVT, so Dr. Rodriguez and coinvestigators decided to conduct a retrospective review of practices at Northwestern Memorial Hospital. He explained the study hypothesis: “Our thinking was that these kinds of thrombi are associated with low risk of propagation and pulmonary embolism, and they can and should be managed conservatively.”

Of 647 patients with isolated thrombosis of the anterior and posterior tibial, soleal, peroneal, or gastrocnemius veins, 44% received an IVC filter, and the rest got medical treatment alone. Of the 362 patients managed medically, 49% received therapeutic anticoagulation, 12% got low-dose prophylactic anticoagulation, and 39% underwent surveillance without anticoagulation.

The primary outcome was the incidence of venous thromboembolic complications – that is, propagation of DVT or pulmonary embolism. The incidence was 35% in the surveillance-only group, 30% with prophylactic anticoagulation, and 10% in patients who got therapeutic anticoagulation.

Of note, the rate of the most feared complication, pulmonary embolism, was low and similar in the filter recipients and medically managed group: 2.5% in the IVC group, 3.3% with medical management.

“Distal vein thromboses have low rates of pulmonary embolism, regardless of whether or not they are so-called protected with a filter. On the other hand, a filter was associated with a 10% rate of complications. I have to make clear that these were radiographic abnormalities – tilting, migration, caval perforation – that didn’t have clinical consequences, but we were very aggressive in removing the IVC filters, and I’m guessing if they’d been left inside they would create problems in the long term,” Dr. Rodriguez said.

An important point about this study is that these were all sick patients, and most were hospitalized. The filter recipients and medical groups differed in key ways. For example, 49% of the filter patients had a malignancy, and 56% had a baseline history of venous thromboembolic events, compared with 26% and 16%, respectively, of the medical group. For that reason, the investigators performed propensity score matching and came up with 157 closely matched patient pairs. The outcomes remained unchanged.

Of course, this was a retrospective study, with its inherent limitations, but Dr. Rodriguez characterized the published randomized trials on management of CVT as “small and limited.” The most frequently quoted study is the double-blind multicenter CACTUS trial, which randomized 252 outpatients with symptomatic CVT to 6 weeks of low-molecular-weight heparin or placebo and found no difference in the rates of proximal extension of venous thromboembolic events (Lancet Haematol. 2016 Dec;3[12]:e556-62). But these were all low-risk patients. Prior DVT or malignancy were exclusion criteria, so this was a very different population than treated at Northwestern.

Based upon the results of the retrospective study at Northwestern, which have been published (J Vasc Surg Venous Lymphat Disord. 2017 Jan;5[1]:25-32), the vascular surgery service has developed a management algorithm for DVT management based upon the lesion site. For acute isolated lower extremity DVT, the algorithm calls for 3 months of therapeutic anticoagulation. If a patient is unable to undergo anticoagulation, venous duplex ultrasound is repeated at 1 week. If the imaging shows propagation into the popliteal vein and anticoagulation remains contraindicated, only then is placement of an IVC filter warranted.

Dr. Rodriguez reported serving as a paid speaker for Abbott, Endologix, and W.L. Gore.

bjancin@frontlinemedcom.com

 

CHICAGO – The use of therapeutic-dose anticoagulation in hospitalized patients with calf vein thrombosis significantly reduces the risk of venous thromboembolic complications, compared with lower-dose prophylactic anticoagulation or surveillance alone, Heron E. Rodriguez, MD, said at a symposium on vascular surgery sponsored by Northwestern University.

Moreover, placement of an inferior vena cava filter in patients with calf vein thrombosis when anticoagulation is contraindicated accomplishes nothing beneficial and had a 10% complication rate in a large retrospective single-center study, added Dr. Rodriguez of Northwestern University, Chicago.

Bruce Jancin/Frontline Medical News

“In our population – patients that are in the hospital with risk factors for venous thromboembolic complications – we think that anticoagulation is a good idea. Low-risk patients or patients in whom anticoagulation is contraindicated should not be getting a filter. There’s really not any advantage in putting in a filter,” the vascular surgeon said.

Deep vein thrombosis (DVT) remains a significant source of morbidity and mortality despite worldwide awareness of the problem.

“Specifically, calf vein thrombosis [CVT] is very common, and we know that in some series up to 30% of patients end up propagating proximally if they’re not treated, and a good number of them develop chronic venous insufficiency, with long-term consequences,” he noted.

“Unfortunately there is no consensus regarding treatment. The guidelines are very vague. For example, there is no mention [in current American College of Chest Physicians guidelines] of how to manage muscular vein thrombosis and much ambiguity on how to treat calf vein thrombosis,” he continued.

Dr. Rodriguez cited as an indication of the lack of consensus on management of CVT a single-institution survey by other investigators of the practices of physicians in various specialties. Forty-nine percent of respondents indicated they anticoagulate patients with CVT; 51% don’t. Of those who did, 62% prescribed low-molecular-weight heparin and 11% intravenous heparin. Fifty-eight percent of physicians who anticoagulated did so for 3 months, 30% for 6. And 46% of physicians used an inferior vena cava (IVC) filter when anticoagulation was contraindicated (Vascular. 2014 Apr;22[2]:93-7).

That rate of IVC placement “seemed really high” given the paucity of supporting evidence for safety and efficacy of filter placement in the setting of CVT, so Dr. Rodriguez and coinvestigators decided to conduct a retrospective review of practices at Northwestern Memorial Hospital. He explained the study hypothesis: “Our thinking was that these kinds of thrombi are associated with low risk of propagation and pulmonary embolism, and they can and should be managed conservatively.”

Of 647 patients with isolated thrombosis of the anterior and posterior tibial, soleal, peroneal, or gastrocnemius veins, 44% received an IVC filter, and the rest got medical treatment alone. Of the 362 patients managed medically, 49% received therapeutic anticoagulation, 12% got low-dose prophylactic anticoagulation, and 39% underwent surveillance without anticoagulation.

The primary outcome was the incidence of venous thromboembolic complications – that is, propagation of DVT or pulmonary embolism. The incidence was 35% in the surveillance-only group, 30% with prophylactic anticoagulation, and 10% in patients who got therapeutic anticoagulation.

Of note, the rate of the most feared complication, pulmonary embolism, was low and similar in the filter recipients and medically managed group: 2.5% in the IVC group, 3.3% with medical management.

“Distal vein thromboses have low rates of pulmonary embolism, regardless of whether or not they are so-called protected with a filter. On the other hand, a filter was associated with a 10% rate of complications. I have to make clear that these were radiographic abnormalities – tilting, migration, caval perforation – that didn’t have clinical consequences, but we were very aggressive in removing the IVC filters, and I’m guessing if they’d been left inside they would create problems in the long term,” Dr. Rodriguez said.

An important point about this study is that these were all sick patients, and most were hospitalized. The filter recipients and medical groups differed in key ways. For example, 49% of the filter patients had a malignancy, and 56% had a baseline history of venous thromboembolic events, compared with 26% and 16%, respectively, of the medical group. For that reason, the investigators performed propensity score matching and came up with 157 closely matched patient pairs. The outcomes remained unchanged.

Of course, this was a retrospective study, with its inherent limitations, but Dr. Rodriguez characterized the published randomized trials on management of CVT as “small and limited.” The most frequently quoted study is the double-blind multicenter CACTUS trial, which randomized 252 outpatients with symptomatic CVT to 6 weeks of low-molecular-weight heparin or placebo and found no difference in the rates of proximal extension of venous thromboembolic events (Lancet Haematol. 2016 Dec;3[12]:e556-62). But these were all low-risk patients. Prior DVT or malignancy were exclusion criteria, so this was a very different population than treated at Northwestern.

Based upon the results of the retrospective study at Northwestern, which have been published (J Vasc Surg Venous Lymphat Disord. 2017 Jan;5[1]:25-32), the vascular surgery service has developed a management algorithm for DVT management based upon the lesion site. For acute isolated lower extremity DVT, the algorithm calls for 3 months of therapeutic anticoagulation. If a patient is unable to undergo anticoagulation, venous duplex ultrasound is repeated at 1 week. If the imaging shows propagation into the popliteal vein and anticoagulation remains contraindicated, only then is placement of an IVC filter warranted.

Dr. Rodriguez reported serving as a paid speaker for Abbott, Endologix, and W.L. Gore.

bjancin@frontlinemedcom.com

 

CHICAGO – The use of therapeutic-dose anticoagulation in hospitalized patients with calf vein thrombosis significantly reduces the risk of venous thromboembolic complications, compared with lower-dose prophylactic anticoagulation or surveillance alone, Heron E. Rodriguez, MD, said at a symposium on vascular surgery sponsored by Northwestern University.

Moreover, placement of an inferior vena cava filter in patients with calf vein thrombosis when anticoagulation is contraindicated accomplishes nothing beneficial and had a 10% complication rate in a large retrospective single-center study, added Dr. Rodriguez of Northwestern University, Chicago.

Bruce Jancin/Frontline Medical News

“In our population – patients that are in the hospital with risk factors for venous thromboembolic complications – we think that anticoagulation is a good idea. Low-risk patients or patients in whom anticoagulation is contraindicated should not be getting a filter. There’s really not any advantage in putting in a filter,” the vascular surgeon said.

Deep vein thrombosis (DVT) remains a significant source of morbidity and mortality despite worldwide awareness of the problem.

“Specifically, calf vein thrombosis [CVT] is very common, and we know that in some series up to 30% of patients end up propagating proximally if they’re not treated, and a good number of them develop chronic venous insufficiency, with long-term consequences,” he noted.

“Unfortunately there is no consensus regarding treatment. The guidelines are very vague. For example, there is no mention [in current American College of Chest Physicians guidelines] of how to manage muscular vein thrombosis and much ambiguity on how to treat calf vein thrombosis,” he continued.

Dr. Rodriguez cited as an indication of the lack of consensus on management of CVT a single-institution survey by other investigators of the practices of physicians in various specialties. Forty-nine percent of respondents indicated they anticoagulate patients with CVT; 51% don’t. Of those who did, 62% prescribed low-molecular-weight heparin and 11% intravenous heparin. Fifty-eight percent of physicians who anticoagulated did so for 3 months, 30% for 6. And 46% of physicians used an inferior vena cava (IVC) filter when anticoagulation was contraindicated (Vascular. 2014 Apr;22[2]:93-7).

That rate of IVC placement “seemed really high” given the paucity of supporting evidence for safety and efficacy of filter placement in the setting of CVT, so Dr. Rodriguez and coinvestigators decided to conduct a retrospective review of practices at Northwestern Memorial Hospital. He explained the study hypothesis: “Our thinking was that these kinds of thrombi are associated with low risk of propagation and pulmonary embolism, and they can and should be managed conservatively.”

Of 647 patients with isolated thrombosis of the anterior and posterior tibial, soleal, peroneal, or gastrocnemius veins, 44% received an IVC filter, and the rest got medical treatment alone. Of the 362 patients managed medically, 49% received therapeutic anticoagulation, 12% got low-dose prophylactic anticoagulation, and 39% underwent surveillance without anticoagulation.

The primary outcome was the incidence of venous thromboembolic complications – that is, propagation of DVT or pulmonary embolism. The incidence was 35% in the surveillance-only group, 30% with prophylactic anticoagulation, and 10% in patients who got therapeutic anticoagulation.

Of note, the rate of the most feared complication, pulmonary embolism, was low and similar in the filter recipients and medically managed group: 2.5% in the IVC group, 3.3% with medical management.

“Distal vein thromboses have low rates of pulmonary embolism, regardless of whether or not they are so-called protected with a filter. On the other hand, a filter was associated with a 10% rate of complications. I have to make clear that these were radiographic abnormalities – tilting, migration, caval perforation – that didn’t have clinical consequences, but we were very aggressive in removing the IVC filters, and I’m guessing if they’d been left inside they would create problems in the long term,” Dr. Rodriguez said.

An important point about this study is that these were all sick patients, and most were hospitalized. The filter recipients and medical groups differed in key ways. For example, 49% of the filter patients had a malignancy, and 56% had a baseline history of venous thromboembolic events, compared with 26% and 16%, respectively, of the medical group. For that reason, the investigators performed propensity score matching and came up with 157 closely matched patient pairs. The outcomes remained unchanged.

Of course, this was a retrospective study, with its inherent limitations, but Dr. Rodriguez characterized the published randomized trials on management of CVT as “small and limited.” The most frequently quoted study is the double-blind multicenter CACTUS trial, which randomized 252 outpatients with symptomatic CVT to 6 weeks of low-molecular-weight heparin or placebo and found no difference in the rates of proximal extension of venous thromboembolic events (Lancet Haematol. 2016 Dec;3[12]:e556-62). But these were all low-risk patients. Prior DVT or malignancy were exclusion criteria, so this was a very different population than treated at Northwestern.

Based upon the results of the retrospective study at Northwestern, which have been published (J Vasc Surg Venous Lymphat Disord. 2017 Jan;5[1]:25-32), the vascular surgery service has developed a management algorithm for DVT management based upon the lesion site. For acute isolated lower extremity DVT, the algorithm calls for 3 months of therapeutic anticoagulation. If a patient is unable to undergo anticoagulation, venous duplex ultrasound is repeated at 1 week. If the imaging shows propagation into the popliteal vein and anticoagulation remains contraindicated, only then is placement of an IVC filter warranted.

Dr. Rodriguez reported serving as a paid speaker for Abbott, Endologix, and W.L. Gore.

bjancin@frontlinemedcom.com

 

ANAHEIM, CALIF. – Eating an ounce and a half of walnuts daily led to favorable changes in gut microbiome composition and diversity in a prospective randomized controlled trial, Klaus G. Parhofer, MD, reported at the American Heart Association scientific session.

These changes in intestinal flora may account for the reductions in LDL cholesterol, triglycerides, apolipoprotein B, and non-HDL cholesterol previously documented with walnut consumption in the same trial, according to Dr. Parhofer, professor of endocrinology and metabolism at the University of Munich.

Bruce Jancin/Frontline Medical News

The study included 204 healthy white men and women with a mean age of 63 years and a mean body mass index of 25.1 kg/m², who were randomized to an 8-week diet that included 43 g of shelled walnuts per day or to an isocaloric nut-free control diet. Then, after a 4-week washout, participants crossed over to the other study arm. Stool samples were collected from 142 subjects at the end of each diet phase for microbiome analysis of bacterial ribosomal RNA.



The gut microbiome composition during the walnut and control phases differed by about 5%. The proportion of the microbiome composed of probiotic and butyric acid–producing organisms in the phylum Bacteroidetes – especially Ruminococcacaeae and Bifidobacteria – increased during the walnut-eating phase, while the Clostridium cluster XIVa microorganisms in the genera Blautia and Anaerostipes decreased significantly, compared with the control diet.

“It is unclear whether these changes are preserved during longer walnut consumption and how these changes can be associated with the observed changes in lipid metabolism,” the endocrinologist noted.

An earlier report focused on the fasting lipid reductions seen in response to walnut consumption in the full study population. LDL cholesterol fell by an average of 7.4 mg/dL after 8 weeks of daily walnut consumption, compared with a 1.7-mg/dL reduction on the nut-free diet; triglycerides fell by 5.0 mg/dL, while increasing by 3.7 mg/dL on the control diet; non-HDL cholesterol declined by 10.3 mg/dL on the walnut diet and by a far more modest 1.4 mg/dL during the control phase; and apolipoprotein B dropped by 6.7 mg/dL compared with a 0.5 mg/dL reduction on the nut-free diet. All of these differences were statistically significant. However, levels of HDL and lipoprotein (a) weren’t affected.

The California Walnut Commission provided Dr. Parhofer with a research grant to conduct the trial.
 

bjancin@frontlinemedcom.com

 

ANAHEIM, CALIF. – Eating an ounce and a half of walnuts daily led to favorable changes in gut microbiome composition and diversity in a prospective randomized controlled trial, Klaus G. Parhofer, MD, reported at the American Heart Association scientific session.

These changes in intestinal flora may account for the reductions in LDL cholesterol, triglycerides, apolipoprotein B, and non-HDL cholesterol previously documented with walnut consumption in the same trial, according to Dr. Parhofer, professor of endocrinology and metabolism at the University of Munich.

Bruce Jancin/Frontline Medical News

The study included 204 healthy white men and women with a mean age of 63 years and a mean body mass index of 25.1 kg/m², who were randomized to an 8-week diet that included 43 g of shelled walnuts per day or to an isocaloric nut-free control diet. Then, after a 4-week washout, participants crossed over to the other study arm. Stool samples were collected from 142 subjects at the end of each diet phase for microbiome analysis of bacterial ribosomal RNA.



The gut microbiome composition during the walnut and control phases differed by about 5%. The proportion of the microbiome composed of probiotic and butyric acid–producing organisms in the phylum Bacteroidetes – especially Ruminococcacaeae and Bifidobacteria – increased during the walnut-eating phase, while the Clostridium cluster XIVa microorganisms in the genera Blautia and Anaerostipes decreased significantly, compared with the control diet.

“It is unclear whether these changes are preserved during longer walnut consumption and how these changes can be associated with the observed changes in lipid metabolism,” the endocrinologist noted.

An earlier report focused on the fasting lipid reductions seen in response to walnut consumption in the full study population. LDL cholesterol fell by an average of 7.4 mg/dL after 8 weeks of daily walnut consumption, compared with a 1.7-mg/dL reduction on the nut-free diet; triglycerides fell by 5.0 mg/dL, while increasing by 3.7 mg/dL on the control diet; non-HDL cholesterol declined by 10.3 mg/dL on the walnut diet and by a far more modest 1.4 mg/dL during the control phase; and apolipoprotein B dropped by 6.7 mg/dL compared with a 0.5 mg/dL reduction on the nut-free diet. All of these differences were statistically significant. However, levels of HDL and lipoprotein (a) weren’t affected.

The California Walnut Commission provided Dr. Parhofer with a research grant to conduct the trial.
 

bjancin@frontlinemedcom.com

 

ANAHEIM, CALIF. – Eating an ounce and a half of walnuts daily led to favorable changes in gut microbiome composition and diversity in a prospective randomized controlled trial, Klaus G. Parhofer, MD, reported at the American Heart Association scientific session.

These changes in intestinal flora may account for the reductions in LDL cholesterol, triglycerides, apolipoprotein B, and non-HDL cholesterol previously documented with walnut consumption in the same trial, according to Dr. Parhofer, professor of endocrinology and metabolism at the University of Munich.

Bruce Jancin/Frontline Medical News

The study included 204 healthy white men and women with a mean age of 63 years and a mean body mass index of 25.1 kg/m², who were randomized to an 8-week diet that included 43 g of shelled walnuts per day or to an isocaloric nut-free control diet. Then, after a 4-week washout, participants crossed over to the other study arm. Stool samples were collected from 142 subjects at the end of each diet phase for microbiome analysis of bacterial ribosomal RNA.



The gut microbiome composition during the walnut and control phases differed by about 5%. The proportion of the microbiome composed of probiotic and butyric acid–producing organisms in the phylum Bacteroidetes – especially Ruminococcacaeae and Bifidobacteria – increased during the walnut-eating phase, while the Clostridium cluster XIVa microorganisms in the genera Blautia and Anaerostipes decreased significantly, compared with the control diet.

“It is unclear whether these changes are preserved during longer walnut consumption and how these changes can be associated with the observed changes in lipid metabolism,” the endocrinologist noted.

An earlier report focused on the fasting lipid reductions seen in response to walnut consumption in the full study population. LDL cholesterol fell by an average of 7.4 mg/dL after 8 weeks of daily walnut consumption, compared with a 1.7-mg/dL reduction on the nut-free diet; triglycerides fell by 5.0 mg/dL, while increasing by 3.7 mg/dL on the control diet; non-HDL cholesterol declined by 10.3 mg/dL on the walnut diet and by a far more modest 1.4 mg/dL during the control phase; and apolipoprotein B dropped by 6.7 mg/dL compared with a 0.5 mg/dL reduction on the nut-free diet. All of these differences were statistically significant. However, levels of HDL and lipoprotein (a) weren’t affected.

The California Walnut Commission provided Dr. Parhofer with a research grant to conduct the trial.
 

bjancin@frontlinemedcom.com

 

ANAHEIM, CALIF. – Adults older than age 75 years with known atherosclerotic cardiovascular disease are significantly less likely than younger patients to receive a high-intensity statin for secondary prevention, even though they actually tolerate statin therapy better, Michael G. Nanna, MD, said at the American Heart Association scientific sessions.

This was among the eye-opening findings from his analysis of data from the PALM (Patient and Provider Assessment of Lipid Management) Registry, a national registry that provides a snapshot of how cardiologists, primary care physicians, and endocrinologists in real-world community practice care for their patients with known atherosclerotic cardiovascular disease (ASCVD) or at high risk for it.

Bruce Jancin/Frontline Medical News

The analysis included 7,736 patients receiving care in 138 U.S. cardiology, primary care, and endocrinology practices, including 1,704 patients over age 75, 1,038 of whom had known ASCVD and thus were candidates for secondary prevention measures, explained Dr. Nanna, a second-year cardiology fellow at Duke University in Durham, N.C.

The impetus for this study was the dearth of information about what’s going on in everyday clinical practice in terms of statin utilization and side effects in the elderly since release of the 2013 American College of Cardiology and American Heart Association cholesterol guidelines. Those guidelines highlighted the lack of randomized clinical trial data to support the use of statins in patients over age 75, who had typically been excluded from participation in the major studies.

The guidelines recommended moderate-intensity statin therapy for secondary prevention in the elderly, and didn’t take a firm position regarding statins for primary prevention in older patients.
 

What’s happening in community practice

For primary prevention in the elderly, physicians appear to be extrapolating from their practice patterns in younger at-risk patients. Sixty-three percent of patients younger than age 75 at high risk for ASCVD were on a statin for primary prevention, as were an equal percentage of older patients. Moreover, 10.2% of older patients were on a high-intensity statin for primary prevention, a rate not significantly different from the 12.3% in younger at-risk patients.

Statin therapy for secondary prevention in the elderly was a different story. Older patients were significantly less likely to receive any statin for secondary prevention. And they were much less likely to get a high-intensity statin, by a margin of 23.5% to 36.2%.

Indeed, in a multivariate regression analysis adjusted for patient demographics, diabetes, smoking, heart failure, body mass index, insurance type, income, and whether a patient saw a cardiologist, older patients with ASCVD were 42% less likely to receive a high-intensity statin than patients younger than age 75.

“It’s interesting that older patients who have ASCVD are actually the group at highest risk of events, yet they’re the least likely to receive a high-intensity statin,” Dr. Nanna observed in an interview.

Of note, older patients were significantly less likely to report any side effect on a statin, by a margin of 41.3% to 46.6%. They were also markedly less likely to report myalgias, by a margin of 23.3% to 33.3%.

“One of the reasons why folks have shied away from treating older patients with statins, and especially with high-intensity statins, is the theoretical risk of more side effects and drug interactions. We didn’t see that,” Dr. Nanna said.
 

What’s next

“My dream is that studies like this will motivate folks to fund a randomized clinical trial looking at high-intensity statins in older adults,” Dr. Nanna said. “I think there are funding challenges because both rosuvastatin and atorvastatin are generic at this point. But I think it needs to be done.”

Rumor has it, he added, that the first randomized trial of statin therapy in the elderly will be in the primary prevention setting. “That’s an area where we’re all essentially operating in an evidence-free zone,” Dr. Nanna said.

Regeneron and Sanofi fund the PALM Registry. Dr. Nanna reported having no relevant financial conflicts of interest.

bjancin@frontlinemedcom.com

 

ANAHEIM, CALIF. – Adults older than age 75 years with known atherosclerotic cardiovascular disease are significantly less likely than younger patients to receive a high-intensity statin for secondary prevention, even though they actually tolerate statin therapy better, Michael G. Nanna, MD, said at the American Heart Association scientific sessions.

This was among the eye-opening findings from his analysis of data from the PALM (Patient and Provider Assessment of Lipid Management) Registry, a national registry that provides a snapshot of how cardiologists, primary care physicians, and endocrinologists in real-world community practice care for their patients with known atherosclerotic cardiovascular disease (ASCVD) or at high risk for it.

Bruce Jancin/Frontline Medical News

The analysis included 7,736 patients receiving care in 138 U.S. cardiology, primary care, and endocrinology practices, including 1,704 patients over age 75, 1,038 of whom had known ASCVD and thus were candidates for secondary prevention measures, explained Dr. Nanna, a second-year cardiology fellow at Duke University in Durham, N.C.

The impetus for this study was the dearth of information about what’s going on in everyday clinical practice in terms of statin utilization and side effects in the elderly since release of the 2013 American College of Cardiology and American Heart Association cholesterol guidelines. Those guidelines highlighted the lack of randomized clinical trial data to support the use of statins in patients over age 75, who had typically been excluded from participation in the major studies.

The guidelines recommended moderate-intensity statin therapy for secondary prevention in the elderly, and didn’t take a firm position regarding statins for primary prevention in older patients.
 

What’s happening in community practice

For primary prevention in the elderly, physicians appear to be extrapolating from their practice patterns in younger at-risk patients. Sixty-three percent of patients younger than age 75 at high risk for ASCVD were on a statin for primary prevention, as were an equal percentage of older patients. Moreover, 10.2% of older patients were on a high-intensity statin for primary prevention, a rate not significantly different from the 12.3% in younger at-risk patients.

Statin therapy for secondary prevention in the elderly was a different story. Older patients were significantly less likely to receive any statin for secondary prevention. And they were much less likely to get a high-intensity statin, by a margin of 23.5% to 36.2%.

Indeed, in a multivariate regression analysis adjusted for patient demographics, diabetes, smoking, heart failure, body mass index, insurance type, income, and whether a patient saw a cardiologist, older patients with ASCVD were 42% less likely to receive a high-intensity statin than patients younger than age 75.

“It’s interesting that older patients who have ASCVD are actually the group at highest risk of events, yet they’re the least likely to receive a high-intensity statin,” Dr. Nanna observed in an interview.

Of note, older patients were significantly less likely to report any side effect on a statin, by a margin of 41.3% to 46.6%. They were also markedly less likely to report myalgias, by a margin of 23.3% to 33.3%.

“One of the reasons why folks have shied away from treating older patients with statins, and especially with high-intensity statins, is the theoretical risk of more side effects and drug interactions. We didn’t see that,” Dr. Nanna said.
 

What’s next

“My dream is that studies like this will motivate folks to fund a randomized clinical trial looking at high-intensity statins in older adults,” Dr. Nanna said. “I think there are funding challenges because both rosuvastatin and atorvastatin are generic at this point. But I think it needs to be done.”

Rumor has it, he added, that the first randomized trial of statin therapy in the elderly will be in the primary prevention setting. “That’s an area where we’re all essentially operating in an evidence-free zone,” Dr. Nanna said.

Regeneron and Sanofi fund the PALM Registry. Dr. Nanna reported having no relevant financial conflicts of interest.

bjancin@frontlinemedcom.com

 

ANAHEIM, CALIF. – Adults older than age 75 years with known atherosclerotic cardiovascular disease are significantly less likely than younger patients to receive a high-intensity statin for secondary prevention, even though they actually tolerate statin therapy better, Michael G. Nanna, MD, said at the American Heart Association scientific sessions.

This was among the eye-opening findings from his analysis of data from the PALM (Patient and Provider Assessment of Lipid Management) Registry, a national registry that provides a snapshot of how cardiologists, primary care physicians, and endocrinologists in real-world community practice care for their patients with known atherosclerotic cardiovascular disease (ASCVD) or at high risk for it.

Bruce Jancin/Frontline Medical News

The analysis included 7,736 patients receiving care in 138 U.S. cardiology, primary care, and endocrinology practices, including 1,704 patients over age 75, 1,038 of whom had known ASCVD and thus were candidates for secondary prevention measures, explained Dr. Nanna, a second-year cardiology fellow at Duke University in Durham, N.C.

The impetus for this study was the dearth of information about what’s going on in everyday clinical practice in terms of statin utilization and side effects in the elderly since release of the 2013 American College of Cardiology and American Heart Association cholesterol guidelines. Those guidelines highlighted the lack of randomized clinical trial data to support the use of statins in patients over age 75, who had typically been excluded from participation in the major studies.

The guidelines recommended moderate-intensity statin therapy for secondary prevention in the elderly, and didn’t take a firm position regarding statins for primary prevention in older patients.
 

What’s happening in community practice

For primary prevention in the elderly, physicians appear to be extrapolating from their practice patterns in younger at-risk patients. Sixty-three percent of patients younger than age 75 at high risk for ASCVD were on a statin for primary prevention, as were an equal percentage of older patients. Moreover, 10.2% of older patients were on a high-intensity statin for primary prevention, a rate not significantly different from the 12.3% in younger at-risk patients.

Statin therapy for secondary prevention in the elderly was a different story. Older patients were significantly less likely to receive any statin for secondary prevention. And they were much less likely to get a high-intensity statin, by a margin of 23.5% to 36.2%.

Indeed, in a multivariate regression analysis adjusted for patient demographics, diabetes, smoking, heart failure, body mass index, insurance type, income, and whether a patient saw a cardiologist, older patients with ASCVD were 42% less likely to receive a high-intensity statin than patients younger than age 75.

“It’s interesting that older patients who have ASCVD are actually the group at highest risk of events, yet they’re the least likely to receive a high-intensity statin,” Dr. Nanna observed in an interview.

Of note, older patients were significantly less likely to report any side effect on a statin, by a margin of 41.3% to 46.6%. They were also markedly less likely to report myalgias, by a margin of 23.3% to 33.3%.

“One of the reasons why folks have shied away from treating older patients with statins, and especially with high-intensity statins, is the theoretical risk of more side effects and drug interactions. We didn’t see that,” Dr. Nanna said.
 

What’s next

“My dream is that studies like this will motivate folks to fund a randomized clinical trial looking at high-intensity statins in older adults,” Dr. Nanna said. “I think there are funding challenges because both rosuvastatin and atorvastatin are generic at this point. But I think it needs to be done.”

Rumor has it, he added, that the first randomized trial of statin therapy in the elderly will be in the primary prevention setting. “That’s an area where we’re all essentially operating in an evidence-free zone,” Dr. Nanna said.

Regeneron and Sanofi fund the PALM Registry. Dr. Nanna reported having no relevant financial conflicts of interest.

bjancin@frontlinemedcom.com

 

CHICAGO – Modern medical management is as effective as carotid artery reintervention for stroke prevention in asymptomatic patients with a carotid in-stent restenosis in excess of 70%, Jayer Chung, MD, asserted at a symposium on vascular surgery sponsored by Northwestern University.

That, in his view, makes medical management the clear preferred strategy.

Bruce Jancin/Frontline Medical News

“A carotid intervention costs about $17,000. If we choose medical management, we can better allocate our resources. Furthermore, if it doesn’t really help, I don’t want to do one of these procedures to my patients. I want to avoid the periprocedural risks. Early on, the stroke and death rates are higher in the intervention arm,” explained Dr. Chung, a vascular surgeon at Baylor College of Medicine, Houston.

A growing body of evidence, mainly from nested cohorts within randomized controlled trials, indicates that the late ipsilateral stroke rate associated with post–carotid endarterectomy restenosis (CEA) is much higher than that for carotid in-stent restenosis (C-ISR). In a recent meta-analysis of nine randomized trials, the difference in risk was more than 10-fold, with a 9.2% stroke rate at a mean of 37 months of follow-up in patients with post-CEA restenosis, compared with a 0.8% rate with 50 months of follow-up in patients with C-ISR (Eur J Vasc Endovasc Surg. 2017 Jun;53[6]:766-75).

“These pathologies behave very, very differently,” Dr. Chung observed. “The C-ISR lesions tend to be less embologenic.”

C-ISR is an uncommon event. Extrapolating from the landmark CREST (Carotid Revascularization Endarterectomy versus Stenting Trial) and other randomized trials, about 6% of patients who undergo percutaneous carotid stenting will be develop C-ISR within 2 years. But since the proportion of all carotid revascularizations that are done by carotid stent angioplasty has steadily increased over the past 15 years as the frequency of CEA has dropped, C-ISR is a problem that vascular specialists will continue to encounter on a regular basis.

Symptomatic C-ISR warrants reintervention; broad agreement exists on that. But there is a paucity of data to guide treatment decisions regarding asymptomatic yet angiographically severe C-ISR. Indeed, Dr. Chung was lead author of the only retrospective study of the natural history of untreated C-ISR, as opposed to carefully selected cohorts from randomized trials involving highly experienced operators. This study was a retrospective review of 59 patients with 75 C-ISRs of at least 50% seen at a single Veterans Affairs medical center over a 13-year period. Three-quarters of the ISRs were asymptomatic.

Forty of the 79 C-ISRs underwent percutaneous intervention at the physician’s discretion. Those patients did not differ from the observation-only group in age, comorbid conditions, type of original stent, or clopidogrel use. Reintervention was safe: There was one stent thrombosis resulting in stroke and death within 30 days in the reintervention group and no 30-day strokes in the observation-only group. During a mean 2.6 years of follow-up, the composite rate of death, stroke, or MI was low and not statistically significantly different between the two groups. Indeed, during up to 13 years of follow-up only one patient with untreated C-ISR experienced an ipsilateral stroke, as did two patients in the percutaneous intervention group (J Vasc Surg. 2016 Nov;64[5]:1286-94).
 

Dr. Chung does the math

According to data from the National Inpatient Sample, vascular surgeons do an average of 15 carotid angioplasty and stenting procedures per year. If 6% of those stents develop in-stent restenosis, and with a number needed to treat with revascularization of 25 to prevent 1 stroke, Dr. Chung estimated that hypothetically it would take the typical vascular surgeon 27 years to prevent one stroke due to C-ISR.

“That’s a very long time to prevent one stroke, in my opinion,” he said.
 

How his study has affected his own practice

Dr. Chung now intervenes only for symptomatic C-ISRs, and only after an affected patient is on optimal medical therapy, including a statin and dual-antiplatelet therapy.

“I try to do an open procedure if possible, especially if the restenosis is above C-2. The ones I tend to do percutaneously are the post-irradiation stenoses or those with excessive scarring, and I use a cerebral protection device,” the surgeon explained.

He emphasized, however, that the final word on the appropriate management of C-ISRs isn’t in yet. A standardized definition of C-ISR is needed, as are multicenter prospective registries of medically managed patients as well as those undergoing various forms of reintervention. And a pathologic study is warranted to confirm the hypothesis that the histopathology of post-CEA and post-stent restenosis – and hence the natural history – is markedly different.

Dr. Chung reported having no financial conflicts regarding his presentation.

bjancin@frontlinemedcom.com

 

CHICAGO – Modern medical management is as effective as carotid artery reintervention for stroke prevention in asymptomatic patients with a carotid in-stent restenosis in excess of 70%, Jayer Chung, MD, asserted at a symposium on vascular surgery sponsored by Northwestern University.

That, in his view, makes medical management the clear preferred strategy.

Bruce Jancin/Frontline Medical News

“A carotid intervention costs about $17,000. If we choose medical management, we can better allocate our resources. Furthermore, if it doesn’t really help, I don’t want to do one of these procedures to my patients. I want to avoid the periprocedural risks. Early on, the stroke and death rates are higher in the intervention arm,” explained Dr. Chung, a vascular surgeon at Baylor College of Medicine, Houston.

A growing body of evidence, mainly from nested cohorts within randomized controlled trials, indicates that the late ipsilateral stroke rate associated with post–carotid endarterectomy restenosis (CEA) is much higher than that for carotid in-stent restenosis (C-ISR). In a recent meta-analysis of nine randomized trials, the difference in risk was more than 10-fold, with a 9.2% stroke rate at a mean of 37 months of follow-up in patients with post-CEA restenosis, compared with a 0.8% rate with 50 months of follow-up in patients with C-ISR (Eur J Vasc Endovasc Surg. 2017 Jun;53[6]:766-75).

“These pathologies behave very, very differently,” Dr. Chung observed. “The C-ISR lesions tend to be less embologenic.”

C-ISR is an uncommon event. Extrapolating from the landmark CREST (Carotid Revascularization Endarterectomy versus Stenting Trial) and other randomized trials, about 6% of patients who undergo percutaneous carotid stenting will be develop C-ISR within 2 years. But since the proportion of all carotid revascularizations that are done by carotid stent angioplasty has steadily increased over the past 15 years as the frequency of CEA has dropped, C-ISR is a problem that vascular specialists will continue to encounter on a regular basis.

Symptomatic C-ISR warrants reintervention; broad agreement exists on that. But there is a paucity of data to guide treatment decisions regarding asymptomatic yet angiographically severe C-ISR. Indeed, Dr. Chung was lead author of the only retrospective study of the natural history of untreated C-ISR, as opposed to carefully selected cohorts from randomized trials involving highly experienced operators. This study was a retrospective review of 59 patients with 75 C-ISRs of at least 50% seen at a single Veterans Affairs medical center over a 13-year period. Three-quarters of the ISRs were asymptomatic.

Forty of the 79 C-ISRs underwent percutaneous intervention at the physician’s discretion. Those patients did not differ from the observation-only group in age, comorbid conditions, type of original stent, or clopidogrel use. Reintervention was safe: There was one stent thrombosis resulting in stroke and death within 30 days in the reintervention group and no 30-day strokes in the observation-only group. During a mean 2.6 years of follow-up, the composite rate of death, stroke, or MI was low and not statistically significantly different between the two groups. Indeed, during up to 13 years of follow-up only one patient with untreated C-ISR experienced an ipsilateral stroke, as did two patients in the percutaneous intervention group (J Vasc Surg. 2016 Nov;64[5]:1286-94).
 

Dr. Chung does the math

According to data from the National Inpatient Sample, vascular surgeons do an average of 15 carotid angioplasty and stenting procedures per year. If 6% of those stents develop in-stent restenosis, and with a number needed to treat with revascularization of 25 to prevent 1 stroke, Dr. Chung estimated that hypothetically it would take the typical vascular surgeon 27 years to prevent one stroke due to C-ISR.

“That’s a very long time to prevent one stroke, in my opinion,” he said.
 

How his study has affected his own practice

Dr. Chung now intervenes only for symptomatic C-ISRs, and only after an affected patient is on optimal medical therapy, including a statin and dual-antiplatelet therapy.

“I try to do an open procedure if possible, especially if the restenosis is above C-2. The ones I tend to do percutaneously are the post-irradiation stenoses or those with excessive scarring, and I use a cerebral protection device,” the surgeon explained.

He emphasized, however, that the final word on the appropriate management of C-ISRs isn’t in yet. A standardized definition of C-ISR is needed, as are multicenter prospective registries of medically managed patients as well as those undergoing various forms of reintervention. And a pathologic study is warranted to confirm the hypothesis that the histopathology of post-CEA and post-stent restenosis – and hence the natural history – is markedly different.

Dr. Chung reported having no financial conflicts regarding his presentation.

bjancin@frontlinemedcom.com

 

CHICAGO – Modern medical management is as effective as carotid artery reintervention for stroke prevention in asymptomatic patients with a carotid in-stent restenosis in excess of 70%, Jayer Chung, MD, asserted at a symposium on vascular surgery sponsored by Northwestern University.

That, in his view, makes medical management the clear preferred strategy.

Bruce Jancin/Frontline Medical News

“A carotid intervention costs about $17,000. If we choose medical management, we can better allocate our resources. Furthermore, if it doesn’t really help, I don’t want to do one of these procedures to my patients. I want to avoid the periprocedural risks. Early on, the stroke and death rates are higher in the intervention arm,” explained Dr. Chung, a vascular surgeon at Baylor College of Medicine, Houston.

A growing body of evidence, mainly from nested cohorts within randomized controlled trials, indicates that the late ipsilateral stroke rate associated with post–carotid endarterectomy restenosis (CEA) is much higher than that for carotid in-stent restenosis (C-ISR). In a recent meta-analysis of nine randomized trials, the difference in risk was more than 10-fold, with a 9.2% stroke rate at a mean of 37 months of follow-up in patients with post-CEA restenosis, compared with a 0.8% rate with 50 months of follow-up in patients with C-ISR (Eur J Vasc Endovasc Surg. 2017 Jun;53[6]:766-75).

“These pathologies behave very, very differently,” Dr. Chung observed. “The C-ISR lesions tend to be less embologenic.”

C-ISR is an uncommon event. Extrapolating from the landmark CREST (Carotid Revascularization Endarterectomy versus Stenting Trial) and other randomized trials, about 6% of patients who undergo percutaneous carotid stenting will be develop C-ISR within 2 years. But since the proportion of all carotid revascularizations that are done by carotid stent angioplasty has steadily increased over the past 15 years as the frequency of CEA has dropped, C-ISR is a problem that vascular specialists will continue to encounter on a regular basis.

Symptomatic C-ISR warrants reintervention; broad agreement exists on that. But there is a paucity of data to guide treatment decisions regarding asymptomatic yet angiographically severe C-ISR. Indeed, Dr. Chung was lead author of the only retrospective study of the natural history of untreated C-ISR, as opposed to carefully selected cohorts from randomized trials involving highly experienced operators. This study was a retrospective review of 59 patients with 75 C-ISRs of at least 50% seen at a single Veterans Affairs medical center over a 13-year period. Three-quarters of the ISRs were asymptomatic.

Forty of the 79 C-ISRs underwent percutaneous intervention at the physician’s discretion. Those patients did not differ from the observation-only group in age, comorbid conditions, type of original stent, or clopidogrel use. Reintervention was safe: There was one stent thrombosis resulting in stroke and death within 30 days in the reintervention group and no 30-day strokes in the observation-only group. During a mean 2.6 years of follow-up, the composite rate of death, stroke, or MI was low and not statistically significantly different between the two groups. Indeed, during up to 13 years of follow-up only one patient with untreated C-ISR experienced an ipsilateral stroke, as did two patients in the percutaneous intervention group (J Vasc Surg. 2016 Nov;64[5]:1286-94).
 

Dr. Chung does the math

According to data from the National Inpatient Sample, vascular surgeons do an average of 15 carotid angioplasty and stenting procedures per year. If 6% of those stents develop in-stent restenosis, and with a number needed to treat with revascularization of 25 to prevent 1 stroke, Dr. Chung estimated that hypothetically it would take the typical vascular surgeon 27 years to prevent one stroke due to C-ISR.

“That’s a very long time to prevent one stroke, in my opinion,” he said.
 

How his study has affected his own practice

Dr. Chung now intervenes only for symptomatic C-ISRs, and only after an affected patient is on optimal medical therapy, including a statin and dual-antiplatelet therapy.

“I try to do an open procedure if possible, especially if the restenosis is above C-2. The ones I tend to do percutaneously are the post-irradiation stenoses or those with excessive scarring, and I use a cerebral protection device,” the surgeon explained.

He emphasized, however, that the final word on the appropriate management of C-ISRs isn’t in yet. A standardized definition of C-ISR is needed, as are multicenter prospective registries of medically managed patients as well as those undergoing various forms of reintervention. And a pathologic study is warranted to confirm the hypothesis that the histopathology of post-CEA and post-stent restenosis – and hence the natural history – is markedly different.

Dr. Chung reported having no financial conflicts regarding his presentation.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – Isolated severe tricuspid regurgitation is a recently recognized, greatly underdiagnosed, and growing problem that’s treatable, provided affected patients are referred for surgery before the clinical course progresses to intractable right heart disease with cirrhosis and liver failure, Rick A. Nishimura, MD, said at the Annual Cardiovascular Conference at Snowmass.

“This is an emerging disease that you’re all going to see in your practices this year. You’ve got to know what to do with these patients. Get to them early,” urged Dr. Nishimura, professor of cardiovascular sciences and hypertension at the Mayo Clinic in Rochester, Minn.

The medical textbooks don’t discuss isolated severe tricuspid regurgitation (ISTR) or its etiology. ISTR is a disorder of progressive right ventricular dilation and dysfunction whose etiology involves either longstanding atrial fibrillation or valvular disruption due to interference from a crossing lead of a permanent pacemaker or implantable cardioverter defibrillator.

“This is something different. These patients have a normal left heart and left heart valves and normal pressures, with no pulmonary hypertension. So it doesn’t fit into any of the textbook categories of tricuspid regurgitation,” the cardiologist said.

Bruce Jancin/Frontline Medical News

Moreover, the current American College of Cardiology/American Heart Association guidelines on valvular heart disease don’t address ISTR, either. Physicians who attempt to apply the guidelines in deciding when to refer a patient with ISTR for surgery will oftentimes find they’ve waited too long and the patient has started to develop end-stage disease, according to Dr. Nishimura.

And he should know: He was lead author of the current ACC/AHA guidelines (J Am Coll Cardiol. 2014 Jun 10;63[22]:2438-88).

Decades ago, Eugene Braunwald, MD, of Harvard Medical School, Boston, famously called the tricuspid valve “the forgotten valve.” The history of the Snowmass winter cardiology conference bears that out. During 2007-2017, the conference featured an average of 5.4 sessions per year on aortic valve disease, 4.5 sessions per year on mitral valve disease, and not a single session on tricuspid valve disease. But the tricuspid valve is forgotten no longer, Dr. Nishimura emphasized.
 

How ISTR presents

The affected patient has a history of either longstanding atrial fibrillation or a permanent pacemaker or ICD.

“This is something that 4 or 5 years ago people said didn’t exist. Our pacemaker people told me, ‘Nah, you can never get tricuspid regurgitation from our leads.’ Now it’s one of the leading causes of tricuspid regurgitation going to operation,” said Dr. Nishimura.

The presenting symptoms of ISTR are typically ascites, edema, and shortness of breath.

“Why should patients with a right heart problem get dyspnea? It turns out that when the right ventricle dilates it pushes the septum in, so the effective operative compliance of the left ventricle decreases and you actually see the pulmonary artery wedge pressure go up,” he explained.

On physical examination, the patient will have elevated jugular venous pressure with large V waves.

“This is a clue that something is going on. The patient will have neck veins jumping up to her ear lobes. The ear lobes are going to wiggle with every heart beat – boom, boom, boom. If you see that, you start to figure out what’s going on. You need nothing else,” Dr. Nishimura said.

The patient will likely also have a pulsatile enlarged liver and, even though this is valve disease, a murmur that’s either soft or inaudible.
 

Echocardiographic diagnosis

Echocardiography will show a dilated right ventricle and right atrium, a dilated inferior vena cava, and a normal left ventricle with no pulmonary hypertension. The classic sign of ISTR on continuous wave Doppler echocardiography is a dagger-shaped tricuspid regurgitation peak velocity signal of less than 2.5 meters/sec, which indicates the absence of pulmonary hypertension. This dagger shape occurs because the right atrial pressure equalizes the right ventricular pressure.

It’s also important to point the echo probe at the hepatic veins to spot another echocardiographic hallmark of ISTR: systolic reversal.

A thorough echo exam makes hemodynamic catheterization unnecessary in these patients, Dr. Nishimura added.
 

When to refer for tricuspid valve repair or replacement

The clinical course of ISTR is progressive, often rapidly so. It starts with elevated jugular venous pressure, then comes fatigue and shortness of breath, moving on to ascites and edema, then finally cirrhosis and renal failure. It’s a vicious cycle in which tricuspid regurgitation begets annular dilation, which causes chordal stretching and worsening tricuspid regurgitation, leading to further annular dilation.

Patients typically aren’t referred for surgery – and may not even present to a physician – until they’ve already developed end-stage disease. That’s probably why the outcomes of surgery for ISTR are so poor. Dr. Nishimura was senior investigator of a recent retrospective study of national trends and outcomes for ISTR surgery based on the National Inpatient Sample. The number of operations increased by 250% during a recent 10-year period, but the surgery is still rare: 290 operations in 2004, climbing to 780 nationwide in 2013.

In-hospital mortality remained steady over time at 8.8%, far higher than rates of in-hospital mortality for surgery for aortic and mitral valve disease, which today stand at 1%-2% or less. The adjusted risk of in-hospital mortality for tricuspid valve replacement in patients with ISTR was 1.9-fold greater than for valve repair (J Am Coll Cardiol. 2017 Dec 19;70[24]:2953-60).

“I think the reason the operative risk of valve surgery for ISTR is so high is that we’re waiting until patients have end-stage disease,” Dr. Nishimura said.

Indeed, he recommends referral for surgery as soon as the echocardiographic diagnosis of ISTR is made in a patient with huge neck veins.

“This will probably take the operative risk down by going to a time when the right ventricle can still recover,” he added.

In a patient with ISTR and pacemaker or defibrillator leads crossing the valve, tricuspid valve repair or replacement should be accompanied by exteriorization of the leads.

Dr. Nishimura reported having no financial conflicts of interest regarding his presentation.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – Isolated severe tricuspid regurgitation is a recently recognized, greatly underdiagnosed, and growing problem that’s treatable, provided affected patients are referred for surgery before the clinical course progresses to intractable right heart disease with cirrhosis and liver failure, Rick A. Nishimura, MD, said at the Annual Cardiovascular Conference at Snowmass.

“This is an emerging disease that you’re all going to see in your practices this year. You’ve got to know what to do with these patients. Get to them early,” urged Dr. Nishimura, professor of cardiovascular sciences and hypertension at the Mayo Clinic in Rochester, Minn.

The medical textbooks don’t discuss isolated severe tricuspid regurgitation (ISTR) or its etiology. ISTR is a disorder of progressive right ventricular dilation and dysfunction whose etiology involves either longstanding atrial fibrillation or valvular disruption due to interference from a crossing lead of a permanent pacemaker or implantable cardioverter defibrillator.

“This is something different. These patients have a normal left heart and left heart valves and normal pressures, with no pulmonary hypertension. So it doesn’t fit into any of the textbook categories of tricuspid regurgitation,” the cardiologist said.

Bruce Jancin/Frontline Medical News

Moreover, the current American College of Cardiology/American Heart Association guidelines on valvular heart disease don’t address ISTR, either. Physicians who attempt to apply the guidelines in deciding when to refer a patient with ISTR for surgery will oftentimes find they’ve waited too long and the patient has started to develop end-stage disease, according to Dr. Nishimura.

And he should know: He was lead author of the current ACC/AHA guidelines (J Am Coll Cardiol. 2014 Jun 10;63[22]:2438-88).

Decades ago, Eugene Braunwald, MD, of Harvard Medical School, Boston, famously called the tricuspid valve “the forgotten valve.” The history of the Snowmass winter cardiology conference bears that out. During 2007-2017, the conference featured an average of 5.4 sessions per year on aortic valve disease, 4.5 sessions per year on mitral valve disease, and not a single session on tricuspid valve disease. But the tricuspid valve is forgotten no longer, Dr. Nishimura emphasized.
 

How ISTR presents

The affected patient has a history of either longstanding atrial fibrillation or a permanent pacemaker or ICD.

“This is something that 4 or 5 years ago people said didn’t exist. Our pacemaker people told me, ‘Nah, you can never get tricuspid regurgitation from our leads.’ Now it’s one of the leading causes of tricuspid regurgitation going to operation,” said Dr. Nishimura.

The presenting symptoms of ISTR are typically ascites, edema, and shortness of breath.

“Why should patients with a right heart problem get dyspnea? It turns out that when the right ventricle dilates it pushes the septum in, so the effective operative compliance of the left ventricle decreases and you actually see the pulmonary artery wedge pressure go up,” he explained.

On physical examination, the patient will have elevated jugular venous pressure with large V waves.

“This is a clue that something is going on. The patient will have neck veins jumping up to her ear lobes. The ear lobes are going to wiggle with every heart beat – boom, boom, boom. If you see that, you start to figure out what’s going on. You need nothing else,” Dr. Nishimura said.

The patient will likely also have a pulsatile enlarged liver and, even though this is valve disease, a murmur that’s either soft or inaudible.
 

Echocardiographic diagnosis

Echocardiography will show a dilated right ventricle and right atrium, a dilated inferior vena cava, and a normal left ventricle with no pulmonary hypertension. The classic sign of ISTR on continuous wave Doppler echocardiography is a dagger-shaped tricuspid regurgitation peak velocity signal of less than 2.5 meters/sec, which indicates the absence of pulmonary hypertension. This dagger shape occurs because the right atrial pressure equalizes the right ventricular pressure.

It’s also important to point the echo probe at the hepatic veins to spot another echocardiographic hallmark of ISTR: systolic reversal.

A thorough echo exam makes hemodynamic catheterization unnecessary in these patients, Dr. Nishimura added.
 

When to refer for tricuspid valve repair or replacement

The clinical course of ISTR is progressive, often rapidly so. It starts with elevated jugular venous pressure, then comes fatigue and shortness of breath, moving on to ascites and edema, then finally cirrhosis and renal failure. It’s a vicious cycle in which tricuspid regurgitation begets annular dilation, which causes chordal stretching and worsening tricuspid regurgitation, leading to further annular dilation.

Patients typically aren’t referred for surgery – and may not even present to a physician – until they’ve already developed end-stage disease. That’s probably why the outcomes of surgery for ISTR are so poor. Dr. Nishimura was senior investigator of a recent retrospective study of national trends and outcomes for ISTR surgery based on the National Inpatient Sample. The number of operations increased by 250% during a recent 10-year period, but the surgery is still rare: 290 operations in 2004, climbing to 780 nationwide in 2013.

In-hospital mortality remained steady over time at 8.8%, far higher than rates of in-hospital mortality for surgery for aortic and mitral valve disease, which today stand at 1%-2% or less. The adjusted risk of in-hospital mortality for tricuspid valve replacement in patients with ISTR was 1.9-fold greater than for valve repair (J Am Coll Cardiol. 2017 Dec 19;70[24]:2953-60).

“I think the reason the operative risk of valve surgery for ISTR is so high is that we’re waiting until patients have end-stage disease,” Dr. Nishimura said.

Indeed, he recommends referral for surgery as soon as the echocardiographic diagnosis of ISTR is made in a patient with huge neck veins.

“This will probably take the operative risk down by going to a time when the right ventricle can still recover,” he added.

In a patient with ISTR and pacemaker or defibrillator leads crossing the valve, tricuspid valve repair or replacement should be accompanied by exteriorization of the leads.

Dr. Nishimura reported having no financial conflicts of interest regarding his presentation.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – Isolated severe tricuspid regurgitation is a recently recognized, greatly underdiagnosed, and growing problem that’s treatable, provided affected patients are referred for surgery before the clinical course progresses to intractable right heart disease with cirrhosis and liver failure, Rick A. Nishimura, MD, said at the Annual Cardiovascular Conference at Snowmass.

“This is an emerging disease that you’re all going to see in your practices this year. You’ve got to know what to do with these patients. Get to them early,” urged Dr. Nishimura, professor of cardiovascular sciences and hypertension at the Mayo Clinic in Rochester, Minn.

The medical textbooks don’t discuss isolated severe tricuspid regurgitation (ISTR) or its etiology. ISTR is a disorder of progressive right ventricular dilation and dysfunction whose etiology involves either longstanding atrial fibrillation or valvular disruption due to interference from a crossing lead of a permanent pacemaker or implantable cardioverter defibrillator.

“This is something different. These patients have a normal left heart and left heart valves and normal pressures, with no pulmonary hypertension. So it doesn’t fit into any of the textbook categories of tricuspid regurgitation,” the cardiologist said.

Bruce Jancin/Frontline Medical News

Moreover, the current American College of Cardiology/American Heart Association guidelines on valvular heart disease don’t address ISTR, either. Physicians who attempt to apply the guidelines in deciding when to refer a patient with ISTR for surgery will oftentimes find they’ve waited too long and the patient has started to develop end-stage disease, according to Dr. Nishimura.

And he should know: He was lead author of the current ACC/AHA guidelines (J Am Coll Cardiol. 2014 Jun 10;63[22]:2438-88).

Decades ago, Eugene Braunwald, MD, of Harvard Medical School, Boston, famously called the tricuspid valve “the forgotten valve.” The history of the Snowmass winter cardiology conference bears that out. During 2007-2017, the conference featured an average of 5.4 sessions per year on aortic valve disease, 4.5 sessions per year on mitral valve disease, and not a single session on tricuspid valve disease. But the tricuspid valve is forgotten no longer, Dr. Nishimura emphasized.
 

How ISTR presents

The affected patient has a history of either longstanding atrial fibrillation or a permanent pacemaker or ICD.

“This is something that 4 or 5 years ago people said didn’t exist. Our pacemaker people told me, ‘Nah, you can never get tricuspid regurgitation from our leads.’ Now it’s one of the leading causes of tricuspid regurgitation going to operation,” said Dr. Nishimura.

The presenting symptoms of ISTR are typically ascites, edema, and shortness of breath.

“Why should patients with a right heart problem get dyspnea? It turns out that when the right ventricle dilates it pushes the septum in, so the effective operative compliance of the left ventricle decreases and you actually see the pulmonary artery wedge pressure go up,” he explained.

On physical examination, the patient will have elevated jugular venous pressure with large V waves.

“This is a clue that something is going on. The patient will have neck veins jumping up to her ear lobes. The ear lobes are going to wiggle with every heart beat – boom, boom, boom. If you see that, you start to figure out what’s going on. You need nothing else,” Dr. Nishimura said.

The patient will likely also have a pulsatile enlarged liver and, even though this is valve disease, a murmur that’s either soft or inaudible.
 

Echocardiographic diagnosis

Echocardiography will show a dilated right ventricle and right atrium, a dilated inferior vena cava, and a normal left ventricle with no pulmonary hypertension. The classic sign of ISTR on continuous wave Doppler echocardiography is a dagger-shaped tricuspid regurgitation peak velocity signal of less than 2.5 meters/sec, which indicates the absence of pulmonary hypertension. This dagger shape occurs because the right atrial pressure equalizes the right ventricular pressure.

It’s also important to point the echo probe at the hepatic veins to spot another echocardiographic hallmark of ISTR: systolic reversal.

A thorough echo exam makes hemodynamic catheterization unnecessary in these patients, Dr. Nishimura added.
 

When to refer for tricuspid valve repair or replacement

The clinical course of ISTR is progressive, often rapidly so. It starts with elevated jugular venous pressure, then comes fatigue and shortness of breath, moving on to ascites and edema, then finally cirrhosis and renal failure. It’s a vicious cycle in which tricuspid regurgitation begets annular dilation, which causes chordal stretching and worsening tricuspid regurgitation, leading to further annular dilation.

Patients typically aren’t referred for surgery – and may not even present to a physician – until they’ve already developed end-stage disease. That’s probably why the outcomes of surgery for ISTR are so poor. Dr. Nishimura was senior investigator of a recent retrospective study of national trends and outcomes for ISTR surgery based on the National Inpatient Sample. The number of operations increased by 250% during a recent 10-year period, but the surgery is still rare: 290 operations in 2004, climbing to 780 nationwide in 2013.

In-hospital mortality remained steady over time at 8.8%, far higher than rates of in-hospital mortality for surgery for aortic and mitral valve disease, which today stand at 1%-2% or less. The adjusted risk of in-hospital mortality for tricuspid valve replacement in patients with ISTR was 1.9-fold greater than for valve repair (J Am Coll Cardiol. 2017 Dec 19;70[24]:2953-60).

“I think the reason the operative risk of valve surgery for ISTR is so high is that we’re waiting until patients have end-stage disease,” Dr. Nishimura said.

Indeed, he recommends referral for surgery as soon as the echocardiographic diagnosis of ISTR is made in a patient with huge neck veins.

“This will probably take the operative risk down by going to a time when the right ventricle can still recover,” he added.

In a patient with ISTR and pacemaker or defibrillator leads crossing the valve, tricuspid valve repair or replacement should be accompanied by exteriorization of the leads.

Dr. Nishimura reported having no financial conflicts of interest regarding his presentation.

bjancin@frontlinemedcom.com

GENEVA – Healthy lifestyle changes produce significant improvement in both psoriasis severity and Dermatologic Life Quality Index scores in obese psoriasis patients, according to a systematic review and meta-analysis presented by Ching-Chi Chi, MD, at the annual congress of the European Academy of Dermatology and Venereology.

A plausible mechanism of benefit exists for these findings: “Fat tissue is known to be an endocrine organ that produces inflammatory cytokines, such as tumor necrosis factor. Reduce the amount of fat tissue and you reduce inflammation,” explained Dr. Chi, professor of dermatology at Chang Gung University in Taoyuan, Taiwan.

jancin

His meta-analysis of 10 randomized, controlled trials totaled 1,163 patients with psoriasis, all with disease sufficiently severe that they were on systemic therapy. Six trials tested dietary interventions, one used a combined diet and exercise program, another involved walking for exercise coupled with continuous health education, and two studies used educational programs promoting healthy lifestyle without coupling to a diet or exercise program.

Among the key findings in the meta-analysis: Participation in dietary interventions provided obese psoriasis patients with a 66% increased likelihood of achieving a PASI 75 response at week 24, compared with controls, with a number needed to treat of 3. These low-calorie diets were typically rigorous, the dermatologist noted. For example, one entailed a food intake of 1,000 kcal/day or less, while another restricted intake by 500 kcal/day less than a patient’s calculated resting energy expenditure.

Also, participants in the dietary intervention studies averaged a 14.4-point improvement from baseline in Dermatologic Life Quality Index (DLQI) scores at week 24 versus a 2.2-point improvement in controls. Researchers consider a 5-point or greater improvement in the DLQI clinically meaningful.

A combined diet and exercise program resulted in a 45% increased likelihood that obese psoriasis patients would achieve a PASI 50 response at week 16, with a number needed to treat of 7. There was a trend in the active treatment arm for higher PASI 75 and PASI 100 responses than in controls as well, but it wasn’t statistically significant.

The one randomized trial of a walking exercise program coupled with continuous health education demonstrated a significant reduction in the rate of psoriasis flares, compared with controls, over a 3-year period.

In contrast, the studies of educational programs promoting a healthy lifestyle without an associated dietary or physical activity intervention failed to show a reduction in PASI scores.

Dr. Chi reported no financial conflicts of interest regarding his study, which was funded by Chang Gung Memorial Hospital.

bjancin@frontlinemedcom.com

SOURCE: Chi C. EADV 2017.

GENEVA – Healthy lifestyle changes produce significant improvement in both psoriasis severity and Dermatologic Life Quality Index scores in obese psoriasis patients, according to a systematic review and meta-analysis presented by Ching-Chi Chi, MD, at the annual congress of the European Academy of Dermatology and Venereology.

A plausible mechanism of benefit exists for these findings: “Fat tissue is known to be an endocrine organ that produces inflammatory cytokines, such as tumor necrosis factor. Reduce the amount of fat tissue and you reduce inflammation,” explained Dr. Chi, professor of dermatology at Chang Gung University in Taoyuan, Taiwan.

jancin

His meta-analysis of 10 randomized, controlled trials totaled 1,163 patients with psoriasis, all with disease sufficiently severe that they were on systemic therapy. Six trials tested dietary interventions, one used a combined diet and exercise program, another involved walking for exercise coupled with continuous health education, and two studies used educational programs promoting healthy lifestyle without coupling to a diet or exercise program.

Among the key findings in the meta-analysis: Participation in dietary interventions provided obese psoriasis patients with a 66% increased likelihood of achieving a PASI 75 response at week 24, compared with controls, with a number needed to treat of 3. These low-calorie diets were typically rigorous, the dermatologist noted. For example, one entailed a food intake of 1,000 kcal/day or less, while another restricted intake by 500 kcal/day less than a patient’s calculated resting energy expenditure.

Also, participants in the dietary intervention studies averaged a 14.4-point improvement from baseline in Dermatologic Life Quality Index (DLQI) scores at week 24 versus a 2.2-point improvement in controls. Researchers consider a 5-point or greater improvement in the DLQI clinically meaningful.

A combined diet and exercise program resulted in a 45% increased likelihood that obese psoriasis patients would achieve a PASI 50 response at week 16, with a number needed to treat of 7. There was a trend in the active treatment arm for higher PASI 75 and PASI 100 responses than in controls as well, but it wasn’t statistically significant.

The one randomized trial of a walking exercise program coupled with continuous health education demonstrated a significant reduction in the rate of psoriasis flares, compared with controls, over a 3-year period.

In contrast, the studies of educational programs promoting a healthy lifestyle without an associated dietary or physical activity intervention failed to show a reduction in PASI scores.

Dr. Chi reported no financial conflicts of interest regarding his study, which was funded by Chang Gung Memorial Hospital.

bjancin@frontlinemedcom.com

SOURCE: Chi C. EADV 2017.

GENEVA – Healthy lifestyle changes produce significant improvement in both psoriasis severity and Dermatologic Life Quality Index scores in obese psoriasis patients, according to a systematic review and meta-analysis presented by Ching-Chi Chi, MD, at the annual congress of the European Academy of Dermatology and Venereology.

A plausible mechanism of benefit exists for these findings: “Fat tissue is known to be an endocrine organ that produces inflammatory cytokines, such as tumor necrosis factor. Reduce the amount of fat tissue and you reduce inflammation,” explained Dr. Chi, professor of dermatology at Chang Gung University in Taoyuan, Taiwan.

jancin

His meta-analysis of 10 randomized, controlled trials totaled 1,163 patients with psoriasis, all with disease sufficiently severe that they were on systemic therapy. Six trials tested dietary interventions, one used a combined diet and exercise program, another involved walking for exercise coupled with continuous health education, and two studies used educational programs promoting healthy lifestyle without coupling to a diet or exercise program.

Among the key findings in the meta-analysis: Participation in dietary interventions provided obese psoriasis patients with a 66% increased likelihood of achieving a PASI 75 response at week 24, compared with controls, with a number needed to treat of 3. These low-calorie diets were typically rigorous, the dermatologist noted. For example, one entailed a food intake of 1,000 kcal/day or less, while another restricted intake by 500 kcal/day less than a patient’s calculated resting energy expenditure.

Also, participants in the dietary intervention studies averaged a 14.4-point improvement from baseline in Dermatologic Life Quality Index (DLQI) scores at week 24 versus a 2.2-point improvement in controls. Researchers consider a 5-point or greater improvement in the DLQI clinically meaningful.

A combined diet and exercise program resulted in a 45% increased likelihood that obese psoriasis patients would achieve a PASI 50 response at week 16, with a number needed to treat of 7. There was a trend in the active treatment arm for higher PASI 75 and PASI 100 responses than in controls as well, but it wasn’t statistically significant.

The one randomized trial of a walking exercise program coupled with continuous health education demonstrated a significant reduction in the rate of psoriasis flares, compared with controls, over a 3-year period.

In contrast, the studies of educational programs promoting a healthy lifestyle without an associated dietary or physical activity intervention failed to show a reduction in PASI scores.

Dr. Chi reported no financial conflicts of interest regarding his study, which was funded by Chang Gung Memorial Hospital.

bjancin@frontlinemedcom.com

SOURCE: Chi C. EADV 2017.

 

GENEVA – Ixekizumab improved fingernail psoriasis significantly faster and with a higher complete nail clearance rate by week 24 compared with ustekinumab in a head-to-head phase 3b randomized trial, Yves Dutronc, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

This is a clinically important finding because – as dermatologists and psoriasis patients well know – nail and skin psoriasis are two different animals.

Bruce Jancin/Frontline Medical News

“Nail involvement is persistent, slow to resolve, difficult to treat, and results in distinct impairment in daily activities,” observed Dr. Dutronc of Eli Lilly in Indianapolis.

He presented a prespecified secondary analysis of the randomized, phase 3b, multicenter IXORA-S trial. The study pit the interleukin-17A inhibitor ixekizumab (Taltz) head-to-head against the interleukin 12/23 inhibitor ustekinumab (Stelara). The primary endpoint, which was the PASI 90 improvement rate, has previously been reported: 73% in the ixekizumab group versus 42% in the ustekinumab group at week 12, and 83% versus 59% at week 24. And ixekizumab’s superior efficacy was achieved with a safety profile similar to that of ustekinumab (Br J Dermatol. 2017 Oct;177[4]:1014-23).

However, change in PASI score or Investigator’s Global Assessment isn’t informative regarding a patient’s change in nail psoriasis status. This was the impetus for the secondary analysis focused on the IXORA-S subgroup with baseline fingernail psoriasis. For this purpose, Dr. Dutronc and his coinvestigators used as their metric the change over time in the Nail Psoriasis Severity Index (NAPSI) total score, which entails a quadrant-by-quadrant assessment of every fingernail.

By play of chance, the 84 patients randomized to ixekizumab had slightly more severe nail psoriasis at baseline than that of the 105 ustekinumab patients. Their mean baseline NAPSI total score was 28.3, compared with 24.8 for the ustekinumab group. More than one-quarter of patients in the ixekizumab arm had a baseline NAPSI score greater than 43, whereas the top quartile of nail psoriasis severity in the ustekinumab group began with a NAPSI score above 34.

Not surprisingly, not much happened in terms of improvement in nail appearance in the first 12 weeks, since new nail grows slowly. But by week 8 the between-group difference in improvement in NAPSI score had become significant in favor of ixekizumab, with a mean 12.9-point reduction from baseline versus a 5.6-point drop in the ustekinumab group. This difference continued to grow over time, such that at week 24 the ixekizumab had a mean 19.9-point reduction, compared with a 13.2-point decrease for the ustekinumab group.

At week 12, 15.5% of the ixekizumab group and 11.3% of the ustekinumab group had reached complete clearance of their fingernail psoriasis. At week 24, complete clearance had been achieved in 48.8% of the ixekizumab group and 22.9% of patients on ustekinumab.

This is an interim analysis. Final results of the IXORA-S nail psoriasis substudy will be reported at 52 weeks of follow-up.
 

bjancin@frontlinemedcom.com

SOURCE: Dutronc Y. https://eadvgeneva2017.org/

 

GENEVA – Ixekizumab improved fingernail psoriasis significantly faster and with a higher complete nail clearance rate by week 24 compared with ustekinumab in a head-to-head phase 3b randomized trial, Yves Dutronc, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

This is a clinically important finding because – as dermatologists and psoriasis patients well know – nail and skin psoriasis are two different animals.

Bruce Jancin/Frontline Medical News

“Nail involvement is persistent, slow to resolve, difficult to treat, and results in distinct impairment in daily activities,” observed Dr. Dutronc of Eli Lilly in Indianapolis.

He presented a prespecified secondary analysis of the randomized, phase 3b, multicenter IXORA-S trial. The study pit the interleukin-17A inhibitor ixekizumab (Taltz) head-to-head against the interleukin 12/23 inhibitor ustekinumab (Stelara). The primary endpoint, which was the PASI 90 improvement rate, has previously been reported: 73% in the ixekizumab group versus 42% in the ustekinumab group at week 12, and 83% versus 59% at week 24. And ixekizumab’s superior efficacy was achieved with a safety profile similar to that of ustekinumab (Br J Dermatol. 2017 Oct;177[4]:1014-23).

However, change in PASI score or Investigator’s Global Assessment isn’t informative regarding a patient’s change in nail psoriasis status. This was the impetus for the secondary analysis focused on the IXORA-S subgroup with baseline fingernail psoriasis. For this purpose, Dr. Dutronc and his coinvestigators used as their metric the change over time in the Nail Psoriasis Severity Index (NAPSI) total score, which entails a quadrant-by-quadrant assessment of every fingernail.

By play of chance, the 84 patients randomized to ixekizumab had slightly more severe nail psoriasis at baseline than that of the 105 ustekinumab patients. Their mean baseline NAPSI total score was 28.3, compared with 24.8 for the ustekinumab group. More than one-quarter of patients in the ixekizumab arm had a baseline NAPSI score greater than 43, whereas the top quartile of nail psoriasis severity in the ustekinumab group began with a NAPSI score above 34.

Not surprisingly, not much happened in terms of improvement in nail appearance in the first 12 weeks, since new nail grows slowly. But by week 8 the between-group difference in improvement in NAPSI score had become significant in favor of ixekizumab, with a mean 12.9-point reduction from baseline versus a 5.6-point drop in the ustekinumab group. This difference continued to grow over time, such that at week 24 the ixekizumab had a mean 19.9-point reduction, compared with a 13.2-point decrease for the ustekinumab group.

At week 12, 15.5% of the ixekizumab group and 11.3% of the ustekinumab group had reached complete clearance of their fingernail psoriasis. At week 24, complete clearance had been achieved in 48.8% of the ixekizumab group and 22.9% of patients on ustekinumab.

This is an interim analysis. Final results of the IXORA-S nail psoriasis substudy will be reported at 52 weeks of follow-up.
 

bjancin@frontlinemedcom.com

SOURCE: Dutronc Y. https://eadvgeneva2017.org/

 

GENEVA – Ixekizumab improved fingernail psoriasis significantly faster and with a higher complete nail clearance rate by week 24 compared with ustekinumab in a head-to-head phase 3b randomized trial, Yves Dutronc, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.

This is a clinically important finding because – as dermatologists and psoriasis patients well know – nail and skin psoriasis are two different animals.

Bruce Jancin/Frontline Medical News

“Nail involvement is persistent, slow to resolve, difficult to treat, and results in distinct impairment in daily activities,” observed Dr. Dutronc of Eli Lilly in Indianapolis.

He presented a prespecified secondary analysis of the randomized, phase 3b, multicenter IXORA-S trial. The study pit the interleukin-17A inhibitor ixekizumab (Taltz) head-to-head against the interleukin 12/23 inhibitor ustekinumab (Stelara). The primary endpoint, which was the PASI 90 improvement rate, has previously been reported: 73% in the ixekizumab group versus 42% in the ustekinumab group at week 12, and 83% versus 59% at week 24. And ixekizumab’s superior efficacy was achieved with a safety profile similar to that of ustekinumab (Br J Dermatol. 2017 Oct;177[4]:1014-23).

However, change in PASI score or Investigator’s Global Assessment isn’t informative regarding a patient’s change in nail psoriasis status. This was the impetus for the secondary analysis focused on the IXORA-S subgroup with baseline fingernail psoriasis. For this purpose, Dr. Dutronc and his coinvestigators used as their metric the change over time in the Nail Psoriasis Severity Index (NAPSI) total score, which entails a quadrant-by-quadrant assessment of every fingernail.

By play of chance, the 84 patients randomized to ixekizumab had slightly more severe nail psoriasis at baseline than that of the 105 ustekinumab patients. Their mean baseline NAPSI total score was 28.3, compared with 24.8 for the ustekinumab group. More than one-quarter of patients in the ixekizumab arm had a baseline NAPSI score greater than 43, whereas the top quartile of nail psoriasis severity in the ustekinumab group began with a NAPSI score above 34.

Not surprisingly, not much happened in terms of improvement in nail appearance in the first 12 weeks, since new nail grows slowly. But by week 8 the between-group difference in improvement in NAPSI score had become significant in favor of ixekizumab, with a mean 12.9-point reduction from baseline versus a 5.6-point drop in the ustekinumab group. This difference continued to grow over time, such that at week 24 the ixekizumab had a mean 19.9-point reduction, compared with a 13.2-point decrease for the ustekinumab group.

At week 12, 15.5% of the ixekizumab group and 11.3% of the ustekinumab group had reached complete clearance of their fingernail psoriasis. At week 24, complete clearance had been achieved in 48.8% of the ixekizumab group and 22.9% of patients on ustekinumab.

This is an interim analysis. Final results of the IXORA-S nail psoriasis substudy will be reported at 52 weeks of follow-up.
 

bjancin@frontlinemedcom.com

SOURCE: Dutronc Y. https://eadvgeneva2017.org/