Mitchel L. Zoler, PhD

ORLANDO – Endoscopic placement of a gastric-jejunal bypass sleeve led to significant weight loss and improvements in diabetes and other comorbidities in a pilot study with 24 patients who had the sleeve in place for up to 1 year.

Endoscopic insertion of the bypass sleeve in these 24 patients involved laparoscopic assistance. Future refinements may eliminate the laparoscopic step and permit a fully nonsurgical approach to gastric bypass, Dr. Bryan J. Sandler said at the American Society for Metabolic and Bariatric Surgery annual meeting. Further study is needed to determine the experience with a larger number of patients and to examine their experience over time, added Dr. Sandler, a bariatric surgeon at the University of California, San Diego.

"It’s a really exciting technology," commented Dr. Aurora D. Pryor, a surgeon in the Center for Metabolic and Weight Loss Surgery at Duke University in Durham, N.C. "It potentially expands the kind of patient in whom you could use this treatment, including bigger, high-risk patients, and possibly also patients with diabetes and a lower body mass index. I would like to see longer-term studies and have them see if they can still successfully exchange the sleeve, but if they can do it successfully long term, then it would be a very innovative solution," she said in an interview.

The study included 24 patients who averaged 40 years old, 71% of whom were women, with an average body mass index of 42 kg/m², with a range of 35-51 kg/m². Twelve patients received a bypass sleeve with a planned explant time of 3 months, and another 12 patients received a sleeve with planned explant time of 12 months. The researchers treated patients at San José Hospital Tec de Monterrey (Mexico).

The surgeons placed the top end of the polyurethane sleeve at the gastroesophageal junction and the bottom end into the jejunum, so that food bypassed most of the stomach and duodenum. The sleeve both restricts food intake and works as a food bypass, mimicking the effect of a surgical Roux-en-Y gastric bypass, Dr. Sandler said.

Among the 12 patients scheduled to have the sleeve in place for 3 months, three required faster removal; two for intolerable nausea and a third because the sleeve returned to the stomach. Among 12 other patients scheduled to have the sleeve in place for 12 months, two required faster removal; one because of nausea and a second because the sleeve returned to the stomach. There were no other serious adverse events, including no perforations, leaks, erosions, ulcerations, obstructions, peritonitis, or pancreatitis. The other 19 patients had their sleeves removed at the scheduled time, a consistently easy process with no indication of attachments formed, he said.

After 3 months, patients lost an average of 39% of their excess weight; at 9 months, they lost an average of 42% of their excess weight.

Eight of the 24 patients who entered the study had diabetes, with an average baseline hemoglobin A_1c of 8.3%, and an average fasting plasma glucose of 152 mg/dL. After 3 months, all eight had improved, and four had complete resolution of their diabetes while off of all medications. Four of these patients had the sleeve in place for 12 months, and after 9 months all four showed improvement, with three having complete resolution of their diabetes.

Dr. Sandler reported similar response patterns for other comorbidities. For example, the study group included 11 patients with hypertension at baseline, and after 3 months, 8 of the 11 were normotensive. Seven of the hypertensive patients kept their sleeves for 12 months, and when their blood pressures were measured after 9 months, five of the seven were normotensive.

The study was funded by ValenTx, the company developing the bypass sleeve. Dr. Sandler said that he has been a consultant to ValenTx. Dr. Pryor said that she has been a consultant to Covidien, Olympus, and W.L. Gore, and she has an ownership interest in TransEnterix.

ORLANDO – Endoscopic placement of a gastric-jejunal bypass sleeve led to significant weight loss and improvements in diabetes and other comorbidities in a pilot study with 24 patients who had the sleeve in place for up to 1 year.

Endoscopic insertion of the bypass sleeve in these 24 patients involved laparoscopic assistance. Future refinements may eliminate the laparoscopic step and permit a fully nonsurgical approach to gastric bypass, Dr. Bryan J. Sandler said at the American Society for Metabolic and Bariatric Surgery annual meeting. Further study is needed to determine the experience with a larger number of patients and to examine their experience over time, added Dr. Sandler, a bariatric surgeon at the University of California, San Diego.

"It’s a really exciting technology," commented Dr. Aurora D. Pryor, a surgeon in the Center for Metabolic and Weight Loss Surgery at Duke University in Durham, N.C. "It potentially expands the kind of patient in whom you could use this treatment, including bigger, high-risk patients, and possibly also patients with diabetes and a lower body mass index. I would like to see longer-term studies and have them see if they can still successfully exchange the sleeve, but if they can do it successfully long term, then it would be a very innovative solution," she said in an interview.

The study included 24 patients who averaged 40 years old, 71% of whom were women, with an average body mass index of 42 kg/m², with a range of 35-51 kg/m². Twelve patients received a bypass sleeve with a planned explant time of 3 months, and another 12 patients received a sleeve with planned explant time of 12 months. The researchers treated patients at San José Hospital Tec de Monterrey (Mexico).

The surgeons placed the top end of the polyurethane sleeve at the gastroesophageal junction and the bottom end into the jejunum, so that food bypassed most of the stomach and duodenum. The sleeve both restricts food intake and works as a food bypass, mimicking the effect of a surgical Roux-en-Y gastric bypass, Dr. Sandler said.

Among the 12 patients scheduled to have the sleeve in place for 3 months, three required faster removal; two for intolerable nausea and a third because the sleeve returned to the stomach. Among 12 other patients scheduled to have the sleeve in place for 12 months, two required faster removal; one because of nausea and a second because the sleeve returned to the stomach. There were no other serious adverse events, including no perforations, leaks, erosions, ulcerations, obstructions, peritonitis, or pancreatitis. The other 19 patients had their sleeves removed at the scheduled time, a consistently easy process with no indication of attachments formed, he said.

After 3 months, patients lost an average of 39% of their excess weight; at 9 months, they lost an average of 42% of their excess weight.

Eight of the 24 patients who entered the study had diabetes, with an average baseline hemoglobin A_1c of 8.3%, and an average fasting plasma glucose of 152 mg/dL. After 3 months, all eight had improved, and four had complete resolution of their diabetes while off of all medications. Four of these patients had the sleeve in place for 12 months, and after 9 months all four showed improvement, with three having complete resolution of their diabetes.

Dr. Sandler reported similar response patterns for other comorbidities. For example, the study group included 11 patients with hypertension at baseline, and after 3 months, 8 of the 11 were normotensive. Seven of the hypertensive patients kept their sleeves for 12 months, and when their blood pressures were measured after 9 months, five of the seven were normotensive.

The study was funded by ValenTx, the company developing the bypass sleeve. Dr. Sandler said that he has been a consultant to ValenTx. Dr. Pryor said that she has been a consultant to Covidien, Olympus, and W.L. Gore, and she has an ownership interest in TransEnterix.

ORLANDO – Endoscopic placement of a gastric-jejunal bypass sleeve led to significant weight loss and improvements in diabetes and other comorbidities in a pilot study with 24 patients who had the sleeve in place for up to 1 year.

Endoscopic insertion of the bypass sleeve in these 24 patients involved laparoscopic assistance. Future refinements may eliminate the laparoscopic step and permit a fully nonsurgical approach to gastric bypass, Dr. Bryan J. Sandler said at the American Society for Metabolic and Bariatric Surgery annual meeting. Further study is needed to determine the experience with a larger number of patients and to examine their experience over time, added Dr. Sandler, a bariatric surgeon at the University of California, San Diego.

"It’s a really exciting technology," commented Dr. Aurora D. Pryor, a surgeon in the Center for Metabolic and Weight Loss Surgery at Duke University in Durham, N.C. "It potentially expands the kind of patient in whom you could use this treatment, including bigger, high-risk patients, and possibly also patients with diabetes and a lower body mass index. I would like to see longer-term studies and have them see if they can still successfully exchange the sleeve, but if they can do it successfully long term, then it would be a very innovative solution," she said in an interview.

The study included 24 patients who averaged 40 years old, 71% of whom were women, with an average body mass index of 42 kg/m², with a range of 35-51 kg/m². Twelve patients received a bypass sleeve with a planned explant time of 3 months, and another 12 patients received a sleeve with planned explant time of 12 months. The researchers treated patients at San José Hospital Tec de Monterrey (Mexico).

The surgeons placed the top end of the polyurethane sleeve at the gastroesophageal junction and the bottom end into the jejunum, so that food bypassed most of the stomach and duodenum. The sleeve both restricts food intake and works as a food bypass, mimicking the effect of a surgical Roux-en-Y gastric bypass, Dr. Sandler said.

Among the 12 patients scheduled to have the sleeve in place for 3 months, three required faster removal; two for intolerable nausea and a third because the sleeve returned to the stomach. Among 12 other patients scheduled to have the sleeve in place for 12 months, two required faster removal; one because of nausea and a second because the sleeve returned to the stomach. There were no other serious adverse events, including no perforations, leaks, erosions, ulcerations, obstructions, peritonitis, or pancreatitis. The other 19 patients had their sleeves removed at the scheduled time, a consistently easy process with no indication of attachments formed, he said.

After 3 months, patients lost an average of 39% of their excess weight; at 9 months, they lost an average of 42% of their excess weight.

Eight of the 24 patients who entered the study had diabetes, with an average baseline hemoglobin A_1c of 8.3%, and an average fasting plasma glucose of 152 mg/dL. After 3 months, all eight had improved, and four had complete resolution of their diabetes while off of all medications. Four of these patients had the sleeve in place for 12 months, and after 9 months all four showed improvement, with three having complete resolution of their diabetes.

Dr. Sandler reported similar response patterns for other comorbidities. For example, the study group included 11 patients with hypertension at baseline, and after 3 months, 8 of the 11 were normotensive. Seven of the hypertensive patients kept their sleeves for 12 months, and when their blood pressures were measured after 9 months, five of the seven were normotensive.

The study was funded by ValenTx, the company developing the bypass sleeve. Dr. Sandler said that he has been a consultant to ValenTx. Dr. Pryor said that she has been a consultant to Covidien, Olympus, and W.L. Gore, and she has an ownership interest in TransEnterix.

ORLANDO – Endoscopic placement of a gastric-jejunal bypass sleeve led to significant weight loss and improvements in diabetes and other comorbidities in a pilot study with 24 patients who had the sleeve in place for up to 1 year.

Endoscopic insertion of the bypass sleeve in these 24 patients involved laparoscopic assistance. Future refinements may eliminate the laparoscopic step and permit a fully nonsurgical approach to gastric bypass, Dr. Bryan J. Sandler said at the American Society for Metabolic and Bariatric Surgery annual meeting. Further study is needed to determine the experience with a larger number of patients and to examine their experience over time, added Dr. Sandler, a bariatric surgeon at the University of California, San Diego.

"It’s a really exciting technology," commented Dr. Aurora D. Pryor, a surgeon in the Center for Metabolic and Weight Loss Surgery at Duke University in Durham, N.C. "It potentially expands the kind of patient in whom you could use this treatment, including bigger, high-risk patients, and possibly also patients with diabetes and a lower body mass index. I would like to see longer-term studies and have them see if they can still successfully exchange the sleeve, but if they can do it successfully long term, then it would be a very innovative solution," she said in an interview.

The study included 24 patients who averaged 40 years old, 71% of whom were women, with an average body mass index of 42 kg/m², with a range of 35-51 kg/m². Twelve patients received a bypass sleeve with a planned explant time of 3 months, and another 12 patients received a sleeve with planned explant time of 12 months. The researchers treated patients at San José Hospital Tec de Monterrey (Mexico).

The surgeons placed the top end of the polyurethane sleeve at the gastroesophageal junction and the bottom end into the jejunum, so that food bypassed most of the stomach and duodenum. The sleeve both restricts food intake and works as a food bypass, mimicking the effect of a surgical Roux-en-Y gastric bypass, Dr. Sandler said.

Among the 12 patients scheduled to have the sleeve in place for 3 months, three required faster removal; two for intolerable nausea and a third because the sleeve returned to the stomach. Among 12 other patients scheduled to have the sleeve in place for 12 months, two required faster removal; one because of nausea and a second because the sleeve returned to the stomach. There were no other serious adverse events, including no perforations, leaks, erosions, ulcerations, obstructions, peritonitis, or pancreatitis. The other 19 patients had their sleeves removed at the scheduled time, a consistently easy process with no indication of attachments formed, he said.

After 3 months, patients lost an average of 39% of their excess weight; at 9 months, they lost an average of 42% of their excess weight.

Eight of the 24 patients who entered the study had diabetes, with an average baseline hemoglobin A_1c of 8.3%, and an average fasting plasma glucose of 152 mg/dL. After 3 months, all eight had improved, and four had complete resolution of their diabetes while off of all medications. Four of these patients had the sleeve in place for 12 months, and after 9 months all four showed improvement, with three having complete resolution of their diabetes.

Dr. Sandler reported similar response patterns for other comorbidities. For example, the study group included 11 patients with hypertension at baseline, and after 3 months, 8 of the 11 were normotensive. Seven of the hypertensive patients kept their sleeves for 12 months, and when their blood pressures were measured after 9 months, five of the seven were normotensive.

The study was funded by ValenTx, the company developing the bypass sleeve. Dr. Sandler said that he has been a consultant to ValenTx. Dr. Pryor said that she has been a consultant to Covidien, Olympus, and W.L. Gore, and she has an ownership interest in TransEnterix.

ORLANDO – Endoscopic placement of a gastric-jejunal bypass sleeve led to significant weight loss and improvements in diabetes and other comorbidities in a pilot study with 24 patients who had the sleeve in place for up to 1 year.

Endoscopic insertion of the bypass sleeve in these 24 patients involved laparoscopic assistance. Future refinements may eliminate the laparoscopic step and permit a fully nonsurgical approach to gastric bypass, Dr. Bryan J. Sandler said at the American Society for Metabolic and Bariatric Surgery annual meeting. Further study is needed to determine the experience with a larger number of patients and to examine their experience over time, added Dr. Sandler, a bariatric surgeon at the University of California, San Diego.

"It’s a really exciting technology," commented Dr. Aurora D. Pryor, a surgeon in the Center for Metabolic and Weight Loss Surgery at Duke University in Durham, N.C. "It potentially expands the kind of patient in whom you could use this treatment, including bigger, high-risk patients, and possibly also patients with diabetes and a lower body mass index. I would like to see longer-term studies and have them see if they can still successfully exchange the sleeve, but if they can do it successfully long term, then it would be a very innovative solution," she said in an interview.

The study included 24 patients who averaged 40 years old, 71% of whom were women, with an average body mass index of 42 kg/m², with a range of 35-51 kg/m². Twelve patients received a bypass sleeve with a planned explant time of 3 months, and another 12 patients received a sleeve with planned explant time of 12 months. The researchers treated patients at San José Hospital Tec de Monterrey (Mexico).

The surgeons placed the top end of the polyurethane sleeve at the gastroesophageal junction and the bottom end into the jejunum, so that food bypassed most of the stomach and duodenum. The sleeve both restricts food intake and works as a food bypass, mimicking the effect of a surgical Roux-en-Y gastric bypass, Dr. Sandler said.

Among the 12 patients scheduled to have the sleeve in place for 3 months, three required faster removal; two for intolerable nausea and a third because the sleeve returned to the stomach. Among 12 other patients scheduled to have the sleeve in place for 12 months, two required faster removal; one because of nausea and a second because the sleeve returned to the stomach. There were no other serious adverse events, including no perforations, leaks, erosions, ulcerations, obstructions, peritonitis, or pancreatitis. The other 19 patients had their sleeves removed at the scheduled time, a consistently easy process with no indication of attachments formed, he said.

After 3 months, patients lost an average of 39% of their excess weight; at 9 months, they lost an average of 42% of their excess weight.

Eight of the 24 patients who entered the study had diabetes, with an average baseline hemoglobin A_1c of 8.3%, and an average fasting plasma glucose of 152 mg/dL. After 3 months, all eight had improved, and four had complete resolution of their diabetes while off of all medications. Four of these patients had the sleeve in place for 12 months, and after 9 months all four showed improvement, with three having complete resolution of their diabetes.

Dr. Sandler reported similar response patterns for other comorbidities. For example, the study group included 11 patients with hypertension at baseline, and after 3 months, 8 of the 11 were normotensive. Seven of the hypertensive patients kept their sleeves for 12 months, and when their blood pressures were measured after 9 months, five of the seven were normotensive.

The study was funded by ValenTx, the company developing the bypass sleeve. Dr. Sandler said that he has been a consultant to ValenTx. Dr. Pryor said that she has been a consultant to Covidien, Olympus, and W.L. Gore, and she has an ownership interest in TransEnterix.

ORLANDO – Endoscopic placement of a gastric-jejunal bypass sleeve led to significant weight loss and improvements in diabetes and other comorbidities in a pilot study with 24 patients who had the sleeve in place for up to 1 year.

Endoscopic insertion of the bypass sleeve in these 24 patients involved laparoscopic assistance. Future refinements may eliminate the laparoscopic step and permit a fully nonsurgical approach to gastric bypass, Dr. Bryan J. Sandler said at the American Society for Metabolic and Bariatric Surgery annual meeting. Further study is needed to determine the experience with a larger number of patients and to examine their experience over time, added Dr. Sandler, a bariatric surgeon at the University of California, San Diego.

"It’s a really exciting technology," commented Dr. Aurora D. Pryor, a surgeon in the Center for Metabolic and Weight Loss Surgery at Duke University in Durham, N.C. "It potentially expands the kind of patient in whom you could use this treatment, including bigger, high-risk patients, and possibly also patients with diabetes and a lower body mass index. I would like to see longer-term studies and have them see if they can still successfully exchange the sleeve, but if they can do it successfully long term, then it would be a very innovative solution," she said in an interview.

The study included 24 patients who averaged 40 years old, 71% of whom were women, with an average body mass index of 42 kg/m², with a range of 35-51 kg/m². Twelve patients received a bypass sleeve with a planned explant time of 3 months, and another 12 patients received a sleeve with planned explant time of 12 months. The researchers treated patients at San José Hospital Tec de Monterrey (Mexico).

The surgeons placed the top end of the polyurethane sleeve at the gastroesophageal junction and the bottom end into the jejunum, so that food bypassed most of the stomach and duodenum. The sleeve both restricts food intake and works as a food bypass, mimicking the effect of a surgical Roux-en-Y gastric bypass, Dr. Sandler said.

Among the 12 patients scheduled to have the sleeve in place for 3 months, three required faster removal; two for intolerable nausea and a third because the sleeve returned to the stomach. Among 12 other patients scheduled to have the sleeve in place for 12 months, two required faster removal; one because of nausea and a second because the sleeve returned to the stomach. There were no other serious adverse events, including no perforations, leaks, erosions, ulcerations, obstructions, peritonitis, or pancreatitis. The other 19 patients had their sleeves removed at the scheduled time, a consistently easy process with no indication of attachments formed, he said.

After 3 months, patients lost an average of 39% of their excess weight; at 9 months, they lost an average of 42% of their excess weight.

Eight of the 24 patients who entered the study had diabetes, with an average baseline hemoglobin A_1c of 8.3%, and an average fasting plasma glucose of 152 mg/dL. After 3 months, all eight had improved, and four had complete resolution of their diabetes while off of all medications. Four of these patients had the sleeve in place for 12 months, and after 9 months all four showed improvement, with three having complete resolution of their diabetes.

Dr. Sandler reported similar response patterns for other comorbidities. For example, the study group included 11 patients with hypertension at baseline, and after 3 months, 8 of the 11 were normotensive. Seven of the hypertensive patients kept their sleeves for 12 months, and when their blood pressures were measured after 9 months, five of the seven were normotensive.

The study was funded by ValenTx, the company developing the bypass sleeve. Dr. Sandler said that he has been a consultant to ValenTx. Dr. Pryor said that she has been a consultant to Covidien, Olympus, and W.L. Gore, and she has an ownership interest in TransEnterix.

Major Finding: Obese patients with a body mass index of 30 kg/m

Data Source: Review of 285 orthotopic liver transplant patients treated at the University of Maryland, Baltimore, during 2000-2008.

Disclosures: Dr. Fayeh said that he had no disclosures.

PHILADELPHIA – Obesity shortens long-term survival in patients undergoing orthotopic liver transplant, according to a review of 285 patients.

One year out from their orthotopic liver transplants, obese transplant recipients (those with a body mass index of 30 kg/m

At 2 years and 5 years after transplantation, survival rates among the obese liver recipients were 67% and 54%, respectively – significantly less than the 79% and 63% survival rates in nonobese patients, said Dr. Fayeh, a transplant surgeon at the University of Maryland.

“I think [obese] patients don't do well because their continued metabolic derangement, such as diabetes and hypercholesterolemia, affects their survival, but we don't have proof of this,” he said. “It is to be determined whether intensive medical therapy, a rehabilitation program, or bariatric surgery post transplant would improve long-term survival.” At the University of Maryland, liver transplants generally are not performed in patients with a body mass index greater than 40 kg/m

Obesity had no impact on short-term survival. At 1 month after transplant, survival rates were 95% among obese recipients and 97% among the nonobese, a difference that was not statistically significant.

During the 9-year period reviewed, 185 nonobese patients and 100 obese patients underwent an orthotopic liver transplant. About a quarter of the patients were at least 60 years old, about a quarter were African American, and slightly more than two-thirds were men. These and other demographic and clinical features were similar in the obese and nonobese subgroups.

Early complications occurred at similar rates in the two subgroups, including the incidence of renal failure, mortality during initial hospitalization, and hospital length of stay. The causes of death throughout the 5-year follow-up were also similar in the two subgroups. The most common causes of death were sepsis, in about 40% of patients, and graft failure, in about a fifth of the patients in both the obese and nonobese subgroups.

In a multivariable analysis, Dr. Fayeh and his associates identified five demographic and clinical features that functioned as independent determinants of mortality: a liver that came from a deceased donor, which boosted the risk for death during follow-up by 2.5-fold; donor age older than 50 years, which boosted the mortality risk 2.4-fold; patient age older than 65, which raised mortality 2.2-fold; cold ischemia time for the transplanted organ exceeding 12 hours, which boosted the mortality rate by 80%; and recipient obesity, which raised the mortality risk by 60%.

The congress was sponsored by the American Society of Transplant Surgeons.

Major Finding: Obese patients with a body mass index of 30 kg/m

Data Source: Review of 285 orthotopic liver transplant patients treated at the University of Maryland, Baltimore, during 2000-2008.

Disclosures: Dr. Fayeh said that he had no disclosures.

PHILADELPHIA – Obesity shortens long-term survival in patients undergoing orthotopic liver transplant, according to a review of 285 patients.

One year out from their orthotopic liver transplants, obese transplant recipients (those with a body mass index of 30 kg/m

At 2 years and 5 years after transplantation, survival rates among the obese liver recipients were 67% and 54%, respectively – significantly less than the 79% and 63% survival rates in nonobese patients, said Dr. Fayeh, a transplant surgeon at the University of Maryland.

“I think [obese] patients don't do well because their continued metabolic derangement, such as diabetes and hypercholesterolemia, affects their survival, but we don't have proof of this,” he said. “It is to be determined whether intensive medical therapy, a rehabilitation program, or bariatric surgery post transplant would improve long-term survival.” At the University of Maryland, liver transplants generally are not performed in patients with a body mass index greater than 40 kg/m

Obesity had no impact on short-term survival. At 1 month after transplant, survival rates were 95% among obese recipients and 97% among the nonobese, a difference that was not statistically significant.

During the 9-year period reviewed, 185 nonobese patients and 100 obese patients underwent an orthotopic liver transplant. About a quarter of the patients were at least 60 years old, about a quarter were African American, and slightly more than two-thirds were men. These and other demographic and clinical features were similar in the obese and nonobese subgroups.

Early complications occurred at similar rates in the two subgroups, including the incidence of renal failure, mortality during initial hospitalization, and hospital length of stay. The causes of death throughout the 5-year follow-up were also similar in the two subgroups. The most common causes of death were sepsis, in about 40% of patients, and graft failure, in about a fifth of the patients in both the obese and nonobese subgroups.

In a multivariable analysis, Dr. Fayeh and his associates identified five demographic and clinical features that functioned as independent determinants of mortality: a liver that came from a deceased donor, which boosted the risk for death during follow-up by 2.5-fold; donor age older than 50 years, which boosted the mortality risk 2.4-fold; patient age older than 65, which raised mortality 2.2-fold; cold ischemia time for the transplanted organ exceeding 12 hours, which boosted the mortality rate by 80%; and recipient obesity, which raised the mortality risk by 60%.

The congress was sponsored by the American Society of Transplant Surgeons.

Major Finding: Obese patients with a body mass index of 30 kg/m

Data Source: Review of 285 orthotopic liver transplant patients treated at the University of Maryland, Baltimore, during 2000-2008.

Disclosures: Dr. Fayeh said that he had no disclosures.

PHILADELPHIA – Obesity shortens long-term survival in patients undergoing orthotopic liver transplant, according to a review of 285 patients.

One year out from their orthotopic liver transplants, obese transplant recipients (those with a body mass index of 30 kg/m

At 2 years and 5 years after transplantation, survival rates among the obese liver recipients were 67% and 54%, respectively – significantly less than the 79% and 63% survival rates in nonobese patients, said Dr. Fayeh, a transplant surgeon at the University of Maryland.

“I think [obese] patients don't do well because their continued metabolic derangement, such as diabetes and hypercholesterolemia, affects their survival, but we don't have proof of this,” he said. “It is to be determined whether intensive medical therapy, a rehabilitation program, or bariatric surgery post transplant would improve long-term survival.” At the University of Maryland, liver transplants generally are not performed in patients with a body mass index greater than 40 kg/m

Obesity had no impact on short-term survival. At 1 month after transplant, survival rates were 95% among obese recipients and 97% among the nonobese, a difference that was not statistically significant.

During the 9-year period reviewed, 185 nonobese patients and 100 obese patients underwent an orthotopic liver transplant. About a quarter of the patients were at least 60 years old, about a quarter were African American, and slightly more than two-thirds were men. These and other demographic and clinical features were similar in the obese and nonobese subgroups.

Early complications occurred at similar rates in the two subgroups, including the incidence of renal failure, mortality during initial hospitalization, and hospital length of stay. The causes of death throughout the 5-year follow-up were also similar in the two subgroups. The most common causes of death were sepsis, in about 40% of patients, and graft failure, in about a fifth of the patients in both the obese and nonobese subgroups.

In a multivariable analysis, Dr. Fayeh and his associates identified five demographic and clinical features that functioned as independent determinants of mortality: a liver that came from a deceased donor, which boosted the risk for death during follow-up by 2.5-fold; donor age older than 50 years, which boosted the mortality risk 2.4-fold; patient age older than 65, which raised mortality 2.2-fold; cold ischemia time for the transplanted organ exceeding 12 hours, which boosted the mortality rate by 80%; and recipient obesity, which raised the mortality risk by 60%.

The congress was sponsored by the American Society of Transplant Surgeons.

ORLANDO – The American Society for Metabolic and Bariatric Surgery has opted to defer making recommendations on the use of the laparoscopically placed gastric band for class I obesity patients, according to Dr. Stacy A. Brethauer, chair of the society's clinical issues committee.

The stage was set for the position statement after the Food and Drug Administration's approval last February of a laparoscopically placed gastric band for patients with class I obesity and a related comorbidity. The society opted to wait, pending availability of level I evidence on the safety and efficacy of at least one alternative surgical option, such as laparoscopic gastric bypass.

“We decided to wait until we had adequate data on at least the bypass,” which should take about another 2 years, given the status of controlled trials now in progress, he said. Safety and efficacy data from randomized, controlled trials of the gastrectomy sleeve will likely take even longer, he added.

“We could issue a statement based just on the band data. There are enough data to say that it's safe and effective. The FDA has spoken, and approved bands for patients with a body mass index (BMI) of 30–34 kg/m

His committee's decision to wait parallels the slow approach that Dr. Brethauer and many of his colleagues have taken on placing bands in the expanded population after the agency's decision last February. This cautious approach reflects both medical insurance coverage issues and the skeptical view of bariatric surgery that many physicians still have, which limits patient referrals.

Despite the FDA's action, class I obesity patients with an obesity-related comorbidity generally still do not receive insurance coverage for band placement, so the only patients of this type getting bands are those who pay for the procedure themselves. “At the Cleveland Clinic, about 5% of our practice is self-pay. We don't see many patients who say, 'I have a BMI of 33 [kg/m

Also, “primary care physicians … still see bariatric surgery as carrying a lot of risk, even for patients with a BMI of more than 35.” As a result, most patients Dr. Brethauer sees about bariatric surgery are self-referred or sent by endocrinologists.

At least some endocrinologists “have realized that there are benefits to patients from bariatric surgery that they can't offer. The endocrinologists will be the [linchpin] for changing the paradigm and getting patients to surgery sooner. The primary care physicians will hopefully follow. Our job [as bariatric surgeons] is to give [these physicians] the evidence so that they can feel comfortable making referrals. Right now, we only see patients with a BMI of 30-35 for entry into trials. We work with endocrinologists” as co-principal investigators of studies in this BMI group.

“The FDA's approval of bands for these patients was based on evidence, but many physicians either don't believe the evidence or don't pay attention to it.”

Dr. Brethauer said that he has received consulting fees from Bard/Davol, Baxter Healthcare, Cardinal Health, Ethicon Endo-Surgery, and Stryker Endoscopy. He also has received honoraria and served on an advisory committee for Ethicon Endo-Surgery, has been a proctor for Bard/Davol, and had received teaching honoraria from Covidien.

'Endocrinologists will be the [linchpin] for changing the paradigm and getting patients to surgery sooner.'

Source DR. BRETHAUER

ORLANDO – The American Society for Metabolic and Bariatric Surgery has opted to defer making recommendations on the use of the laparoscopically placed gastric band for class I obesity patients, according to Dr. Stacy A. Brethauer, chair of the society's clinical issues committee.

The stage was set for the position statement after the Food and Drug Administration's approval last February of a laparoscopically placed gastric band for patients with class I obesity and a related comorbidity. The society opted to wait, pending availability of level I evidence on the safety and efficacy of at least one alternative surgical option, such as laparoscopic gastric bypass.

“We decided to wait until we had adequate data on at least the bypass,” which should take about another 2 years, given the status of controlled trials now in progress, he said. Safety and efficacy data from randomized, controlled trials of the gastrectomy sleeve will likely take even longer, he added.

“We could issue a statement based just on the band data. There are enough data to say that it's safe and effective. The FDA has spoken, and approved bands for patients with a body mass index (BMI) of 30–34 kg/m

His committee's decision to wait parallels the slow approach that Dr. Brethauer and many of his colleagues have taken on placing bands in the expanded population after the agency's decision last February. This cautious approach reflects both medical insurance coverage issues and the skeptical view of bariatric surgery that many physicians still have, which limits patient referrals.

Despite the FDA's action, class I obesity patients with an obesity-related comorbidity generally still do not receive insurance coverage for band placement, so the only patients of this type getting bands are those who pay for the procedure themselves. “At the Cleveland Clinic, about 5% of our practice is self-pay. We don't see many patients who say, 'I have a BMI of 33 [kg/m

Also, “primary care physicians … still see bariatric surgery as carrying a lot of risk, even for patients with a BMI of more than 35.” As a result, most patients Dr. Brethauer sees about bariatric surgery are self-referred or sent by endocrinologists.

At least some endocrinologists “have realized that there are benefits to patients from bariatric surgery that they can't offer. The endocrinologists will be the [linchpin] for changing the paradigm and getting patients to surgery sooner. The primary care physicians will hopefully follow. Our job [as bariatric surgeons] is to give [these physicians] the evidence so that they can feel comfortable making referrals. Right now, we only see patients with a BMI of 30-35 for entry into trials. We work with endocrinologists” as co-principal investigators of studies in this BMI group.

“The FDA's approval of bands for these patients was based on evidence, but many physicians either don't believe the evidence or don't pay attention to it.”

Dr. Brethauer said that he has received consulting fees from Bard/Davol, Baxter Healthcare, Cardinal Health, Ethicon Endo-Surgery, and Stryker Endoscopy. He also has received honoraria and served on an advisory committee for Ethicon Endo-Surgery, has been a proctor for Bard/Davol, and had received teaching honoraria from Covidien.

'Endocrinologists will be the [linchpin] for changing the paradigm and getting patients to surgery sooner.'

Source DR. BRETHAUER

ORLANDO – The American Society for Metabolic and Bariatric Surgery has opted to defer making recommendations on the use of the laparoscopically placed gastric band for class I obesity patients, according to Dr. Stacy A. Brethauer, chair of the society's clinical issues committee.

The stage was set for the position statement after the Food and Drug Administration's approval last February of a laparoscopically placed gastric band for patients with class I obesity and a related comorbidity. The society opted to wait, pending availability of level I evidence on the safety and efficacy of at least one alternative surgical option, such as laparoscopic gastric bypass.

“We decided to wait until we had adequate data on at least the bypass,” which should take about another 2 years, given the status of controlled trials now in progress, he said. Safety and efficacy data from randomized, controlled trials of the gastrectomy sleeve will likely take even longer, he added.

“We could issue a statement based just on the band data. There are enough data to say that it's safe and effective. The FDA has spoken, and approved bands for patients with a body mass index (BMI) of 30–34 kg/m

His committee's decision to wait parallels the slow approach that Dr. Brethauer and many of his colleagues have taken on placing bands in the expanded population after the agency's decision last February. This cautious approach reflects both medical insurance coverage issues and the skeptical view of bariatric surgery that many physicians still have, which limits patient referrals.

Despite the FDA's action, class I obesity patients with an obesity-related comorbidity generally still do not receive insurance coverage for band placement, so the only patients of this type getting bands are those who pay for the procedure themselves. “At the Cleveland Clinic, about 5% of our practice is self-pay. We don't see many patients who say, 'I have a BMI of 33 [kg/m

Also, “primary care physicians … still see bariatric surgery as carrying a lot of risk, even for patients with a BMI of more than 35.” As a result, most patients Dr. Brethauer sees about bariatric surgery are self-referred or sent by endocrinologists.

At least some endocrinologists “have realized that there are benefits to patients from bariatric surgery that they can't offer. The endocrinologists will be the [linchpin] for changing the paradigm and getting patients to surgery sooner. The primary care physicians will hopefully follow. Our job [as bariatric surgeons] is to give [these physicians] the evidence so that they can feel comfortable making referrals. Right now, we only see patients with a BMI of 30-35 for entry into trials. We work with endocrinologists” as co-principal investigators of studies in this BMI group.

“The FDA's approval of bands for these patients was based on evidence, but many physicians either don't believe the evidence or don't pay attention to it.”

Dr. Brethauer said that he has received consulting fees from Bard/Davol, Baxter Healthcare, Cardinal Health, Ethicon Endo-Surgery, and Stryker Endoscopy. He also has received honoraria and served on an advisory committee for Ethicon Endo-Surgery, has been a proctor for Bard/Davol, and had received teaching honoraria from Covidien.

'Endocrinologists will be the [linchpin] for changing the paradigm and getting patients to surgery sooner.'

Source DR. BRETHAUER

Major Finding: During the year following giving birth, women had a statistically significant, 2.4-fold increased risk of incident ACPA-negative rheumatoid arthritis, compared with nulliparous women.

Data Source: Case-control study of 1,205 Swedish women enrolled in the Epidemiological Investigation of Rheumatoid Arthritis study during 1996–2006.

Disclosures: Dr. Bengtsson said that she had no relevant financial disclosures.

LONDON – Women who give birth to a child face a twofold increased risk of incident anticitrullinated peptide antibody–negative rheumatoid arthritis, compared with nulliparous women, but they have no increased risk for developing ACPA-positive disease, based on results from a Swedish epidemiologic study.

The finding is consistent with a report last year from a Norwegian study that women face about a twofold increased risk for incident rheumatoid arthritis (RA) during the first 2 years after giving birth to a child, compared with their RA risk 2–4 years post partum (Ann. Rheum. Dis. 2010;69:332–6). The reason why the new analysis, which included more than 1,200 cases and controls, showed a different relationship between partum and the onset of ACPA-positive RA and ACPA-negative RA remains unclear, according to Camilla Bengtsson, Ph.D.

“Why there is only an association with ACPA-negative disease, and which biological mechanisms are involved remains to be elucidated,” said Dr. Bengtsson, a researcher at the Karolinska Institute in Stockholm. The way in which this finding might apply to practice also remains unclear, she added.

Dr. Bengtsson's analysis failed to show an increased incidence of any form of RA in women who were more than a year out from their delivery.

The study used data and blood specimens from Swedish women aged 18–50 years who were enrolled in the Epidemiological Investigation of RA (EIRA) study during 1996–2006. Among the women with incident RA enrolled in EIRA, 547 (95%) agreed to participate and provide blood specimens, and among the control women in the study, 658 (81%) provided blood. The analysis divided the cases and controls into subgroups based on their partum status. The 547 women with new-onset RA included 360 who had given birth and 187 who had not. The parous women included 226 with ACPA-positive RA and 134 with the ACPA-negative form. Among the nulliparous women with RA, 127 had the ACPA-positive form and 60 were ACPA negative.

Among the controls with no RA, 431 had given birth and 227 had never given birth.

The case-control analysis showed that among all women with incident RA, birth status during the year preceding a new RA diagnosis had no statistically significant relationship with RA onset. However, among women who developed ACPA-negative RA, their risk spiked by a statistically significant, 2.4-fold rate during the year following partum, compared with nulliparous women. In contrast, the incidence of ACPA-positive RA showed no significant relationship to partum status during the preceding year.

Further analysis examined the timing between delivery and onset of ACPA-negative RA more closely. Again, the analysis showed that, during the year following giving birth, women faced a statistically significant, 2.4-fold elevated risk for incident ACPA-negative RA, compared with nulliparous women. During the 2–10 years following giving birth, the rate of incident ACPA-negative RA dropped to a 50% higher risk, compared with nulliparous women, but this difference was not considered statistically significant. And women more than 10 years out from their most recent delivery had a risk for incident ACPA-negative RA identical to the nulliparous women, Dr. Bengtsson reported.

Major Finding: During the year following giving birth, women had a statistically significant, 2.4-fold increased risk of incident ACPA-negative rheumatoid arthritis, compared with nulliparous women.

Data Source: Case-control study of 1,205 Swedish women enrolled in the Epidemiological Investigation of Rheumatoid Arthritis study during 1996–2006.

Disclosures: Dr. Bengtsson said that she had no relevant financial disclosures.

LONDON – Women who give birth to a child face a twofold increased risk of incident anticitrullinated peptide antibody–negative rheumatoid arthritis, compared with nulliparous women, but they have no increased risk for developing ACPA-positive disease, based on results from a Swedish epidemiologic study.

The finding is consistent with a report last year from a Norwegian study that women face about a twofold increased risk for incident rheumatoid arthritis (RA) during the first 2 years after giving birth to a child, compared with their RA risk 2–4 years post partum (Ann. Rheum. Dis. 2010;69:332–6). The reason why the new analysis, which included more than 1,200 cases and controls, showed a different relationship between partum and the onset of ACPA-positive RA and ACPA-negative RA remains unclear, according to Camilla Bengtsson, Ph.D.

“Why there is only an association with ACPA-negative disease, and which biological mechanisms are involved remains to be elucidated,” said Dr. Bengtsson, a researcher at the Karolinska Institute in Stockholm. The way in which this finding might apply to practice also remains unclear, she added.

Dr. Bengtsson's analysis failed to show an increased incidence of any form of RA in women who were more than a year out from their delivery.

The study used data and blood specimens from Swedish women aged 18–50 years who were enrolled in the Epidemiological Investigation of RA (EIRA) study during 1996–2006. Among the women with incident RA enrolled in EIRA, 547 (95%) agreed to participate and provide blood specimens, and among the control women in the study, 658 (81%) provided blood. The analysis divided the cases and controls into subgroups based on their partum status. The 547 women with new-onset RA included 360 who had given birth and 187 who had not. The parous women included 226 with ACPA-positive RA and 134 with the ACPA-negative form. Among the nulliparous women with RA, 127 had the ACPA-positive form and 60 were ACPA negative.

Among the controls with no RA, 431 had given birth and 227 had never given birth.

The case-control analysis showed that among all women with incident RA, birth status during the year preceding a new RA diagnosis had no statistically significant relationship with RA onset. However, among women who developed ACPA-negative RA, their risk spiked by a statistically significant, 2.4-fold rate during the year following partum, compared with nulliparous women. In contrast, the incidence of ACPA-positive RA showed no significant relationship to partum status during the preceding year.

Further analysis examined the timing between delivery and onset of ACPA-negative RA more closely. Again, the analysis showed that, during the year following giving birth, women faced a statistically significant, 2.4-fold elevated risk for incident ACPA-negative RA, compared with nulliparous women. During the 2–10 years following giving birth, the rate of incident ACPA-negative RA dropped to a 50% higher risk, compared with nulliparous women, but this difference was not considered statistically significant. And women more than 10 years out from their most recent delivery had a risk for incident ACPA-negative RA identical to the nulliparous women, Dr. Bengtsson reported.

Major Finding: During the year following giving birth, women had a statistically significant, 2.4-fold increased risk of incident ACPA-negative rheumatoid arthritis, compared with nulliparous women.

Data Source: Case-control study of 1,205 Swedish women enrolled in the Epidemiological Investigation of Rheumatoid Arthritis study during 1996–2006.

Disclosures: Dr. Bengtsson said that she had no relevant financial disclosures.

LONDON – Women who give birth to a child face a twofold increased risk of incident anticitrullinated peptide antibody–negative rheumatoid arthritis, compared with nulliparous women, but they have no increased risk for developing ACPA-positive disease, based on results from a Swedish epidemiologic study.

The finding is consistent with a report last year from a Norwegian study that women face about a twofold increased risk for incident rheumatoid arthritis (RA) during the first 2 years after giving birth to a child, compared with their RA risk 2–4 years post partum (Ann. Rheum. Dis. 2010;69:332–6). The reason why the new analysis, which included more than 1,200 cases and controls, showed a different relationship between partum and the onset of ACPA-positive RA and ACPA-negative RA remains unclear, according to Camilla Bengtsson, Ph.D.

“Why there is only an association with ACPA-negative disease, and which biological mechanisms are involved remains to be elucidated,” said Dr. Bengtsson, a researcher at the Karolinska Institute in Stockholm. The way in which this finding might apply to practice also remains unclear, she added.

Dr. Bengtsson's analysis failed to show an increased incidence of any form of RA in women who were more than a year out from their delivery.

The study used data and blood specimens from Swedish women aged 18–50 years who were enrolled in the Epidemiological Investigation of RA (EIRA) study during 1996–2006. Among the women with incident RA enrolled in EIRA, 547 (95%) agreed to participate and provide blood specimens, and among the control women in the study, 658 (81%) provided blood. The analysis divided the cases and controls into subgroups based on their partum status. The 547 women with new-onset RA included 360 who had given birth and 187 who had not. The parous women included 226 with ACPA-positive RA and 134 with the ACPA-negative form. Among the nulliparous women with RA, 127 had the ACPA-positive form and 60 were ACPA negative.

Among the controls with no RA, 431 had given birth and 227 had never given birth.

The case-control analysis showed that among all women with incident RA, birth status during the year preceding a new RA diagnosis had no statistically significant relationship with RA onset. However, among women who developed ACPA-negative RA, their risk spiked by a statistically significant, 2.4-fold rate during the year following partum, compared with nulliparous women. In contrast, the incidence of ACPA-positive RA showed no significant relationship to partum status during the preceding year.

Further analysis examined the timing between delivery and onset of ACPA-negative RA more closely. Again, the analysis showed that, during the year following giving birth, women faced a statistically significant, 2.4-fold elevated risk for incident ACPA-negative RA, compared with nulliparous women. During the 2–10 years following giving birth, the rate of incident ACPA-negative RA dropped to a 50% higher risk, compared with nulliparous women, but this difference was not considered statistically significant. And women more than 10 years out from their most recent delivery had a risk for incident ACPA-negative RA identical to the nulliparous women, Dr. Bengtsson reported.

PHILADELPHIA – Women who become pregnant after receiving a transplanted liver face an elevated risk of graft rejection, especially during or immediately following the pregnancy, based on a review of 161 U.S. cases.

“The data suggest poorer outcomes for both mothers and their newborns in female liver recipients with risk factors for graft loss within 5 years post pregnancy,” Dr. Carlo B. Ramirez said at the meeting.

“The findings highlight the high-risk nature of this group, warranting closer follow-up of both mother and child,” said Dr. Ramirez, a transplant surgeon at Thomas Jefferson University, Philadelphia.

Of the 161 women who became pregnant following a liver transplant and were enrolled in the National Transplantation Pregnancy Registry (in place since 1991), 16 (10%) lost their graft within 5 years following their first posttransplant pregnancy. The pregnancy and the 3 months following pregnancy posed a particular risk, with half of the women who eventually lost their graft experiencing rejection during that time. In a multivariate model that took into account baseline risk factors, women with a liver transplant faced a 14-fold increased risk for graft loss during the pregnancy, Dr. Ramirez said.

“A lot of patients who have a stable equilibrium with their graft may destabilize under stress. It is possible that there is low-grade, clinically insignificant rejection in some of these patients prior to pregnancy” that then becomes exacerbated by the stress of pregnancy, commented Dr. Jean C. Emond, professor of surgery and director of transplantation at Columbia University in New York. Dr. Emond suggested that a liver biopsy prior to pregnancy might be warranted to assess the stability of the transplant.

Other risk factors for graft loss included younger age of the mother and low gestational age at the time of delivery. In the multivariate analysis, the risk for graft loss fell by a statistically significant 26% for each additional year of age for the mother. Graft loss fell by a statistically significant 5% for each additional week of gestational age when delivery occurred.

Among the 16 women who lost their graft during pregnancy or the following 5 years, their average age when they conceived was 22 years old, compared with an average age of 28 years among the 145 women who did not lose their graft. Average gestational age at delivery was 33 weeks among the women who lost their graft, and 37 weeks among the women who did not lose their graft.

The average age of the women at the time they received their liver transplant was 18 years among those who later lost their grafts, and 23 years among those who retained their grafts. However, the average time between transplantation and conception was an identical 4.3 years in both groups.

The only other risk factor for graft loss that approached statistical significance in the multivariate model was viral hepatitis as the etiologic agent for the liver failure that led to the transplants. Viral hepatitis was the cause of liver failure for six (38%) of the women who lost their grafts following pregnancy, and for 23 (16%) of the women who did not lose their grafts. In the multivariate model, viral hepatitis as the cause of liver failure was linked with a nearly fourfold increased risk for women losing their graft during or after pregnancy, but this relationship failed to meet the standard criterion for statistical significance, Dr. Ramirez said.

The congress was sponsored by the American Society of Transplant Surgeons. Dr. Ramirez said he had no disclosures. The National Transplantation Pregnancy Registry has been supported by grants from Novartis, Astellas, Genentech, Pfizer, Teva, and Sandoz.

PHILADELPHIA – Women who become pregnant after receiving a transplanted liver face an elevated risk of graft rejection, especially during or immediately following the pregnancy, based on a review of 161 U.S. cases.

“The data suggest poorer outcomes for both mothers and their newborns in female liver recipients with risk factors for graft loss within 5 years post pregnancy,” Dr. Carlo B. Ramirez said at the meeting.

“The findings highlight the high-risk nature of this group, warranting closer follow-up of both mother and child,” said Dr. Ramirez, a transplant surgeon at Thomas Jefferson University, Philadelphia.

Of the 161 women who became pregnant following a liver transplant and were enrolled in the National Transplantation Pregnancy Registry (in place since 1991), 16 (10%) lost their graft within 5 years following their first posttransplant pregnancy. The pregnancy and the 3 months following pregnancy posed a particular risk, with half of the women who eventually lost their graft experiencing rejection during that time. In a multivariate model that took into account baseline risk factors, women with a liver transplant faced a 14-fold increased risk for graft loss during the pregnancy, Dr. Ramirez said.

“A lot of patients who have a stable equilibrium with their graft may destabilize under stress. It is possible that there is low-grade, clinically insignificant rejection in some of these patients prior to pregnancy” that then becomes exacerbated by the stress of pregnancy, commented Dr. Jean C. Emond, professor of surgery and director of transplantation at Columbia University in New York. Dr. Emond suggested that a liver biopsy prior to pregnancy might be warranted to assess the stability of the transplant.

Other risk factors for graft loss included younger age of the mother and low gestational age at the time of delivery. In the multivariate analysis, the risk for graft loss fell by a statistically significant 26% for each additional year of age for the mother. Graft loss fell by a statistically significant 5% for each additional week of gestational age when delivery occurred.

Among the 16 women who lost their graft during pregnancy or the following 5 years, their average age when they conceived was 22 years old, compared with an average age of 28 years among the 145 women who did not lose their graft. Average gestational age at delivery was 33 weeks among the women who lost their graft, and 37 weeks among the women who did not lose their graft.

The average age of the women at the time they received their liver transplant was 18 years among those who later lost their grafts, and 23 years among those who retained their grafts. However, the average time between transplantation and conception was an identical 4.3 years in both groups.

The only other risk factor for graft loss that approached statistical significance in the multivariate model was viral hepatitis as the etiologic agent for the liver failure that led to the transplants. Viral hepatitis was the cause of liver failure for six (38%) of the women who lost their grafts following pregnancy, and for 23 (16%) of the women who did not lose their grafts. In the multivariate model, viral hepatitis as the cause of liver failure was linked with a nearly fourfold increased risk for women losing their graft during or after pregnancy, but this relationship failed to meet the standard criterion for statistical significance, Dr. Ramirez said.

The congress was sponsored by the American Society of Transplant Surgeons. Dr. Ramirez said he had no disclosures. The National Transplantation Pregnancy Registry has been supported by grants from Novartis, Astellas, Genentech, Pfizer, Teva, and Sandoz.

PHILADELPHIA – Women who become pregnant after receiving a transplanted liver face an elevated risk of graft rejection, especially during or immediately following the pregnancy, based on a review of 161 U.S. cases.

“The data suggest poorer outcomes for both mothers and their newborns in female liver recipients with risk factors for graft loss within 5 years post pregnancy,” Dr. Carlo B. Ramirez said at the meeting.

“The findings highlight the high-risk nature of this group, warranting closer follow-up of both mother and child,” said Dr. Ramirez, a transplant surgeon at Thomas Jefferson University, Philadelphia.

Of the 161 women who became pregnant following a liver transplant and were enrolled in the National Transplantation Pregnancy Registry (in place since 1991), 16 (10%) lost their graft within 5 years following their first posttransplant pregnancy. The pregnancy and the 3 months following pregnancy posed a particular risk, with half of the women who eventually lost their graft experiencing rejection during that time. In a multivariate model that took into account baseline risk factors, women with a liver transplant faced a 14-fold increased risk for graft loss during the pregnancy, Dr. Ramirez said.

“A lot of patients who have a stable equilibrium with their graft may destabilize under stress. It is possible that there is low-grade, clinically insignificant rejection in some of these patients prior to pregnancy” that then becomes exacerbated by the stress of pregnancy, commented Dr. Jean C. Emond, professor of surgery and director of transplantation at Columbia University in New York. Dr. Emond suggested that a liver biopsy prior to pregnancy might be warranted to assess the stability of the transplant.

Other risk factors for graft loss included younger age of the mother and low gestational age at the time of delivery. In the multivariate analysis, the risk for graft loss fell by a statistically significant 26% for each additional year of age for the mother. Graft loss fell by a statistically significant 5% for each additional week of gestational age when delivery occurred.

Among the 16 women who lost their graft during pregnancy or the following 5 years, their average age when they conceived was 22 years old, compared with an average age of 28 years among the 145 women who did not lose their graft. Average gestational age at delivery was 33 weeks among the women who lost their graft, and 37 weeks among the women who did not lose their graft.

The average age of the women at the time they received their liver transplant was 18 years among those who later lost their grafts, and 23 years among those who retained their grafts. However, the average time between transplantation and conception was an identical 4.3 years in both groups.

The only other risk factor for graft loss that approached statistical significance in the multivariate model was viral hepatitis as the etiologic agent for the liver failure that led to the transplants. Viral hepatitis was the cause of liver failure for six (38%) of the women who lost their grafts following pregnancy, and for 23 (16%) of the women who did not lose their grafts. In the multivariate model, viral hepatitis as the cause of liver failure was linked with a nearly fourfold increased risk for women losing their graft during or after pregnancy, but this relationship failed to meet the standard criterion for statistical significance, Dr. Ramirez said.

The congress was sponsored by the American Society of Transplant Surgeons. Dr. Ramirez said he had no disclosures. The National Transplantation Pregnancy Registry has been supported by grants from Novartis, Astellas, Genentech, Pfizer, Teva, and Sandoz.

Major Finding: During the 5- to 10-year period of extended, continuous treatment with strontium ranelate, postmenopausal women with osteoporosis at baseline had a 21% rate of vertebral fractures and a 14% rate of nonvertebral fractures, significantly less than the 28% and 20% rates, respectively, of fractures in a matched placebo group.

Data Source: Cohort of 233 postmenopausal women with osteoporosis maintained on 2 g/day strontium ranelate for 10 years, compared with a matched control group of 458 women drawn from a pivotal trial of strontium ranelate.

Disclosures: The SOTI and TROPOS trials were funded by Servier, which markets strontium ranelate (Protelos). Dr. Reginster reported financial relationships with Amgen, Analis, Bristol-Myers Squibb, Ebewe, Genévrier, GlaxoSmith-Kline, IBSA, Eli Lilly, Merck Sharp & Dohme, Merckle, Negma, Novartis, Novo Nordisk, NPS Pharmaceuticals, Nycomed, Roche, Rottapharm, Servier, Teijin, Teva, Theramex, Wyeth, UCB, and Zodiac.

LONDON – Strontium ranelate continued to safely and effectively prevent vertebral and nonvertebral fractures in postmenopausal women with osteoporosis during 5–10 years of continuous treatment, in a “modified” case-control study that included 233 women who maintained daily 2-g/day strontium dosing for 10 years.

“Strontium ranelate should not be considered a second-line alternative to bisphosphonates or to any other [osteoporosis] treatment,” Dr. Jean-Yves Reginster said at the meeting.

Treatment with strontium ranelate “gives you a chance to bring bone turnover back to premenopausal values,” said Dr. Reginster, professor of epidemiology and chairman of the department of public health at the University of Liège in Belgium.

The ability of strontium ranelate to maintain a reduced rate of both vertebral and nonvertebral fractures over 10 years of continuous use in this study marks the first reported evidence of an antiosteoporotic drug exerting an unequivocal antifracture benefit for such a prolonged period.

The only other report on 10-year treatment came from the Fracture Intervention Trial Long Term Extension, which included 1,099 women randomized to alendronate or placebo for 10 years (JAMA 2006;296:2927-38).

Those results showed that 5–10 years of extended alendronate treatment did not result in a reduction of all clinical fractures or nonvertebral fracture, compared with women maintained on placebo during years 5–10, but extended alendronate did reduce the clinical vertebral fracture rate, compared with placebo.

“In our study [of strontium ranelate], we had no placebo group, but we showed that you can reduce fractures over 10 years with this drug.”

Strontium maintained its efficacy over 10 years “probably because of its mechanism of action, a dual action,” Dr. Reginster said in an interview.

“With bisphosphonates you reduce bone resorption. With strontium ranelate you reduce bone resorption by 20%–25%, and you increase bone formation by 20%–25%, so you bring the bone back to what you see in younger women. I think it is a more physiologic approach” than treatment with a bisphosphonate.

In addition, “safety is most important to me when you treat for 10 years. One of the biggest advantages of strontium ranelate is that it is a very safe drug, with little risk of adverse effects over time. I think that calculating the risk/benefit ratio of a drug over time is very important.”

In his report, Dr. Reginster emphasized that the women maintained on the drug for 10 years did not have a single episode of atypical fracture, osteonecrosis of the jaw, or atrial fibrillation, and their adverse-event profile showed better safety than in the original, pivotal trials of strontium ranelate.

He also noted that while the extension included only 233 women on the drug, registry data on about one million patients who have taken the drug also show no reported cases of atypical fracture, osteonecrosis of the jaw, or atrial fibrillation.

The 233 women followed for 10 years on continuous strontium ranelate treatment came from either of the two pivotal, 5-year trials of the drug: the Treatment of Peripheral Osteoporosis Study (TROPOS) (J. Clin. Endocrinol. Met. 2005;90:2816-22), and the Spinal Osteoporosis Therapeutic Intervention (SOTI) trial (New. Engl. J. Med. 2004;350:459-68).

They continued to receive 2 g/day strontium ranelate, and 73% of the women completed the full extension period. Their average duration of drug use was 9.8 years, and their average compliance with the regimen was 89%.

During their additional 5 years on the drug, average lumbar spine bone mineral density continued to rise, increasing from about 20% above baseline at the start of the extension to about 27% above baseline at 10 years.

To assess the efficacy of treatment for preventing vertebral and nonvertebral fractures, Dr. Reginster and his associates “rebuilt” a control population by selecting placebo patients from the TROPOS trial who matched the 233 extended-treatment women based on their baseline Fracture Risk Assessment scores.

The researchers matched two TROPOS placebo-group women with each woman in the extension study, assembling a total of 458 controls.

The incidence of vertebral fractures during years 5–10 in the women on strontium ranelate was 21%, compared with a 28% rate in the rebuilt control group, a statistically significant difference.

In addition, the 21% reduction during the 5 to 10- year period was statistically similar to the 19% vertebral fracture rate among women treated during 0–5 years in SOTI.

The incidence of nonvertebral fractures during years 5–10 with strontium ranelate was 14%, significantly less than the 20% rate in the derived placebo group and statistically similar to the 13% rate seen in TROPOS, Dr. Reginster reported.

Major Finding: During the 5- to 10-year period of extended, continuous treatment with strontium ranelate, postmenopausal women with osteoporosis at baseline had a 21% rate of vertebral fractures and a 14% rate of nonvertebral fractures, significantly less than the 28% and 20% rates, respectively, of fractures in a matched placebo group.

Data Source: Cohort of 233 postmenopausal women with osteoporosis maintained on 2 g/day strontium ranelate for 10 years, compared with a matched control group of 458 women drawn from a pivotal trial of strontium ranelate.

Disclosures: The SOTI and TROPOS trials were funded by Servier, which markets strontium ranelate (Protelos). Dr. Reginster reported financial relationships with Amgen, Analis, Bristol-Myers Squibb, Ebewe, Genévrier, GlaxoSmith-Kline, IBSA, Eli Lilly, Merck Sharp & Dohme, Merckle, Negma, Novartis, Novo Nordisk, NPS Pharmaceuticals, Nycomed, Roche, Rottapharm, Servier, Teijin, Teva, Theramex, Wyeth, UCB, and Zodiac.

LONDON – Strontium ranelate continued to safely and effectively prevent vertebral and nonvertebral fractures in postmenopausal women with osteoporosis during 5–10 years of continuous treatment, in a “modified” case-control study that included 233 women who maintained daily 2-g/day strontium dosing for 10 years.

“Strontium ranelate should not be considered a second-line alternative to bisphosphonates or to any other [osteoporosis] treatment,” Dr. Jean-Yves Reginster said at the meeting.

Treatment with strontium ranelate “gives you a chance to bring bone turnover back to premenopausal values,” said Dr. Reginster, professor of epidemiology and chairman of the department of public health at the University of Liège in Belgium.

The ability of strontium ranelate to maintain a reduced rate of both vertebral and nonvertebral fractures over 10 years of continuous use in this study marks the first reported evidence of an antiosteoporotic drug exerting an unequivocal antifracture benefit for such a prolonged period.

The only other report on 10-year treatment came from the Fracture Intervention Trial Long Term Extension, which included 1,099 women randomized to alendronate or placebo for 10 years (JAMA 2006;296:2927-38).

Those results showed that 5–10 years of extended alendronate treatment did not result in a reduction of all clinical fractures or nonvertebral fracture, compared with women maintained on placebo during years 5–10, but extended alendronate did reduce the clinical vertebral fracture rate, compared with placebo.

“In our study [of strontium ranelate], we had no placebo group, but we showed that you can reduce fractures over 10 years with this drug.”

Strontium maintained its efficacy over 10 years “probably because of its mechanism of action, a dual action,” Dr. Reginster said in an interview.

“With bisphosphonates you reduce bone resorption. With strontium ranelate you reduce bone resorption by 20%–25%, and you increase bone formation by 20%–25%, so you bring the bone back to what you see in younger women. I think it is a more physiologic approach” than treatment with a bisphosphonate.

In addition, “safety is most important to me when you treat for 10 years. One of the biggest advantages of strontium ranelate is that it is a very safe drug, with little risk of adverse effects over time. I think that calculating the risk/benefit ratio of a drug over time is very important.”

In his report, Dr. Reginster emphasized that the women maintained on the drug for 10 years did not have a single episode of atypical fracture, osteonecrosis of the jaw, or atrial fibrillation, and their adverse-event profile showed better safety than in the original, pivotal trials of strontium ranelate.

He also noted that while the extension included only 233 women on the drug, registry data on about one million patients who have taken the drug also show no reported cases of atypical fracture, osteonecrosis of the jaw, or atrial fibrillation.

The 233 women followed for 10 years on continuous strontium ranelate treatment came from either of the two pivotal, 5-year trials of the drug: the Treatment of Peripheral Osteoporosis Study (TROPOS) (J. Clin. Endocrinol. Met. 2005;90:2816-22), and the Spinal Osteoporosis Therapeutic Intervention (SOTI) trial (New. Engl. J. Med. 2004;350:459-68).

They continued to receive 2 g/day strontium ranelate, and 73% of the women completed the full extension period. Their average duration of drug use was 9.8 years, and their average compliance with the regimen was 89%.

During their additional 5 years on the drug, average lumbar spine bone mineral density continued to rise, increasing from about 20% above baseline at the start of the extension to about 27% above baseline at 10 years.

To assess the efficacy of treatment for preventing vertebral and nonvertebral fractures, Dr. Reginster and his associates “rebuilt” a control population by selecting placebo patients from the TROPOS trial who matched the 233 extended-treatment women based on their baseline Fracture Risk Assessment scores.

The researchers matched two TROPOS placebo-group women with each woman in the extension study, assembling a total of 458 controls.

The incidence of vertebral fractures during years 5–10 in the women on strontium ranelate was 21%, compared with a 28% rate in the rebuilt control group, a statistically significant difference.

In addition, the 21% reduction during the 5 to 10- year period was statistically similar to the 19% vertebral fracture rate among women treated during 0–5 years in SOTI.

The incidence of nonvertebral fractures during years 5–10 with strontium ranelate was 14%, significantly less than the 20% rate in the derived placebo group and statistically similar to the 13% rate seen in TROPOS, Dr. Reginster reported.

Major Finding: During the 5- to 10-year period of extended, continuous treatment with strontium ranelate, postmenopausal women with osteoporosis at baseline had a 21% rate of vertebral fractures and a 14% rate of nonvertebral fractures, significantly less than the 28% and 20% rates, respectively, of fractures in a matched placebo group.

Data Source: Cohort of 233 postmenopausal women with osteoporosis maintained on 2 g/day strontium ranelate for 10 years, compared with a matched control group of 458 women drawn from a pivotal trial of strontium ranelate.

Disclosures: The SOTI and TROPOS trials were funded by Servier, which markets strontium ranelate (Protelos). Dr. Reginster reported financial relationships with Amgen, Analis, Bristol-Myers Squibb, Ebewe, Genévrier, GlaxoSmith-Kline, IBSA, Eli Lilly, Merck Sharp & Dohme, Merckle, Negma, Novartis, Novo Nordisk, NPS Pharmaceuticals, Nycomed, Roche, Rottapharm, Servier, Teijin, Teva, Theramex, Wyeth, UCB, and Zodiac.

LONDON – Strontium ranelate continued to safely and effectively prevent vertebral and nonvertebral fractures in postmenopausal women with osteoporosis during 5–10 years of continuous treatment, in a “modified” case-control study that included 233 women who maintained daily 2-g/day strontium dosing for 10 years.

“Strontium ranelate should not be considered a second-line alternative to bisphosphonates or to any other [osteoporosis] treatment,” Dr. Jean-Yves Reginster said at the meeting.

Treatment with strontium ranelate “gives you a chance to bring bone turnover back to premenopausal values,” said Dr. Reginster, professor of epidemiology and chairman of the department of public health at the University of Liège in Belgium.

The ability of strontium ranelate to maintain a reduced rate of both vertebral and nonvertebral fractures over 10 years of continuous use in this study marks the first reported evidence of an antiosteoporotic drug exerting an unequivocal antifracture benefit for such a prolonged period.

The only other report on 10-year treatment came from the Fracture Intervention Trial Long Term Extension, which included 1,099 women randomized to alendronate or placebo for 10 years (JAMA 2006;296:2927-38).

Those results showed that 5–10 years of extended alendronate treatment did not result in a reduction of all clinical fractures or nonvertebral fracture, compared with women maintained on placebo during years 5–10, but extended alendronate did reduce the clinical vertebral fracture rate, compared with placebo.

“In our study [of strontium ranelate], we had no placebo group, but we showed that you can reduce fractures over 10 years with this drug.”

Strontium maintained its efficacy over 10 years “probably because of its mechanism of action, a dual action,” Dr. Reginster said in an interview.

“With bisphosphonates you reduce bone resorption. With strontium ranelate you reduce bone resorption by 20%–25%, and you increase bone formation by 20%–25%, so you bring the bone back to what you see in younger women. I think it is a more physiologic approach” than treatment with a bisphosphonate.

In addition, “safety is most important to me when you treat for 10 years. One of the biggest advantages of strontium ranelate is that it is a very safe drug, with little risk of adverse effects over time. I think that calculating the risk/benefit ratio of a drug over time is very important.”

In his report, Dr. Reginster emphasized that the women maintained on the drug for 10 years did not have a single episode of atypical fracture, osteonecrosis of the jaw, or atrial fibrillation, and their adverse-event profile showed better safety than in the original, pivotal trials of strontium ranelate.

He also noted that while the extension included only 233 women on the drug, registry data on about one million patients who have taken the drug also show no reported cases of atypical fracture, osteonecrosis of the jaw, or atrial fibrillation.

The 233 women followed for 10 years on continuous strontium ranelate treatment came from either of the two pivotal, 5-year trials of the drug: the Treatment of Peripheral Osteoporosis Study (TROPOS) (J. Clin. Endocrinol. Met. 2005;90:2816-22), and the Spinal Osteoporosis Therapeutic Intervention (SOTI) trial (New. Engl. J. Med. 2004;350:459-68).

They continued to receive 2 g/day strontium ranelate, and 73% of the women completed the full extension period. Their average duration of drug use was 9.8 years, and their average compliance with the regimen was 89%.

During their additional 5 years on the drug, average lumbar spine bone mineral density continued to rise, increasing from about 20% above baseline at the start of the extension to about 27% above baseline at 10 years.

To assess the efficacy of treatment for preventing vertebral and nonvertebral fractures, Dr. Reginster and his associates “rebuilt” a control population by selecting placebo patients from the TROPOS trial who matched the 233 extended-treatment women based on their baseline Fracture Risk Assessment scores.

The researchers matched two TROPOS placebo-group women with each woman in the extension study, assembling a total of 458 controls.

The incidence of vertebral fractures during years 5–10 in the women on strontium ranelate was 21%, compared with a 28% rate in the rebuilt control group, a statistically significant difference.

In addition, the 21% reduction during the 5 to 10- year period was statistically similar to the 19% vertebral fracture rate among women treated during 0–5 years in SOTI.

The incidence of nonvertebral fractures during years 5–10 with strontium ranelate was 14%, significantly less than the 20% rate in the derived placebo group and statistically similar to the 13% rate seen in TROPOS, Dr. Reginster reported.

Major Finding: A review of 17 recent clinical trials for three new rheumatoid arthritis drugs showed that only two of the trials placed patients randomized into the comparator arms on active drug regimens.

Data Source: Review of publicly reported trial data.

Disclosures: Dr. Juche said that he has received travel support from Actelion.

LONDON – Many recently performed rheumatology drug trials have run into the ethical trap of treating control patients with an ineffective regimen, with the result that some patients experienced ongoing pain and joint dysfunction and continued disease progression.

“I would propose that we change the trial design for the placebo control to use an active comparator against the [investigational] drug,” Dr. Aaron Juche said while presenting a poster at the meeting.

For studies testing a new drug aimed at controlling rheumatoid arthritis pain, dysfunction, and progression, “the standard of care would be a tumor necrosis factor [TNF] inhibitor as the active comparator,” said Dr. Juche, a rheumatologist at Johanniter Hospital in Treuenbrietzen, Germany. Because TNF inhibitors are so effective, a study that uses this treatment in the comparator arm would likely have to be a noninferiority study and would also probably have to involve a relatively large number of patients, he said in an interview.

The standard approach for drug-trial design in patients with RA in recent years has been to follow a model that's more than a decade old, dating back to the first studies on TNF inhibitors during the 1990s: “Patients who did not adequately respond to immunosuppressive drugs were randomly assigned to either an experimental condition under which they received the new substance, or to a control condition under which they continued their formerly inefficient treatment and received a placebo.”

To more systematically assess the scope of the problem, he and his associate reviewed 17 recent, published clinical trials that drug companies used to document the safety and efficacy of three new drugs, abatacept, golimumab, and tocilizumab, to the European Medicines Agencies. Dr. Juche said these studies fairly represented most recently performed drug efficacy trials for patients with RA.

Of the seven studies he reviewed that tested abatacept, none used a control therapy that effectively treated the patients' disease. In all seven studies, patients remained on treatment with a disease-modifying antirheumatic drug (DMARD) that they had already failed on, most commonly methotrexate. During these studies, “patients experienced a persistent, high disease activity,” he reported.

Among four pivotal studies involving golimumab, one enrolled methotrexate-naive patients and then used methotrexate as the control drug. The other three used control groups that received placebo and nothing else or placebo plus methotrexate for enrolled patients who had already failed methotrexate.

A similar pattern existed for the six studies of tocilizumab that Dr. Juche reviewed.

One of the six used methotrexate as the comparator in a trial that enrolled methotrexate-naive patients. The other five studies used comparator groups on either placebo alone or placebo plus a DMARD to which the patient had already not responded.

Dr. Juche added that rheumatology is not unique in having so many of its trials involve ineffective regimens in the control groups.

New drugs should be compared with a TNF inhibitor, suggested Dr. Aaron Juche.

Source Mitchel L. Zoler/Elsevier Global Medical News

Major Finding: A review of 17 recent clinical trials for three new rheumatoid arthritis drugs showed that only two of the trials placed patients randomized into the comparator arms on active drug regimens.

Data Source: Review of publicly reported trial data.

Disclosures: Dr. Juche said that he has received travel support from Actelion.

LONDON – Many recently performed rheumatology drug trials have run into the ethical trap of treating control patients with an ineffective regimen, with the result that some patients experienced ongoing pain and joint dysfunction and continued disease progression.

“I would propose that we change the trial design for the placebo control to use an active comparator against the [investigational] drug,” Dr. Aaron Juche said while presenting a poster at the meeting.

For studies testing a new drug aimed at controlling rheumatoid arthritis pain, dysfunction, and progression, “the standard of care would be a tumor necrosis factor [TNF] inhibitor as the active comparator,” said Dr. Juche, a rheumatologist at Johanniter Hospital in Treuenbrietzen, Germany. Because TNF inhibitors are so effective, a study that uses this treatment in the comparator arm would likely have to be a noninferiority study and would also probably have to involve a relatively large number of patients, he said in an interview.

The standard approach for drug-trial design in patients with RA in recent years has been to follow a model that's more than a decade old, dating back to the first studies on TNF inhibitors during the 1990s: “Patients who did not adequately respond to immunosuppressive drugs were randomly assigned to either an experimental condition under which they received the new substance, or to a control condition under which they continued their formerly inefficient treatment and received a placebo.”

To more systematically assess the scope of the problem, he and his associate reviewed 17 recent, published clinical trials that drug companies used to document the safety and efficacy of three new drugs, abatacept, golimumab, and tocilizumab, to the European Medicines Agencies. Dr. Juche said these studies fairly represented most recently performed drug efficacy trials for patients with RA.

Of the seven studies he reviewed that tested abatacept, none used a control therapy that effectively treated the patients' disease. In all seven studies, patients remained on treatment with a disease-modifying antirheumatic drug (DMARD) that they had already failed on, most commonly methotrexate. During these studies, “patients experienced a persistent, high disease activity,” he reported.

Among four pivotal studies involving golimumab, one enrolled methotrexate-naive patients and then used methotrexate as the control drug. The other three used control groups that received placebo and nothing else or placebo plus methotrexate for enrolled patients who had already failed methotrexate.

A similar pattern existed for the six studies of tocilizumab that Dr. Juche reviewed.

One of the six used methotrexate as the comparator in a trial that enrolled methotrexate-naive patients. The other five studies used comparator groups on either placebo alone or placebo plus a DMARD to which the patient had already not responded.

Dr. Juche added that rheumatology is not unique in having so many of its trials involve ineffective regimens in the control groups.

New drugs should be compared with a TNF inhibitor, suggested Dr. Aaron Juche.

Source Mitchel L. Zoler/Elsevier Global Medical News

Major Finding: A review of 17 recent clinical trials for three new rheumatoid arthritis drugs showed that only two of the trials placed patients randomized into the comparator arms on active drug regimens.

Data Source: Review of publicly reported trial data.

Disclosures: Dr. Juche said that he has received travel support from Actelion.

LONDON – Many recently performed rheumatology drug trials have run into the ethical trap of treating control patients with an ineffective regimen, with the result that some patients experienced ongoing pain and joint dysfunction and continued disease progression.

“I would propose that we change the trial design for the placebo control to use an active comparator against the [investigational] drug,” Dr. Aaron Juche said while presenting a poster at the meeting.

For studies testing a new drug aimed at controlling rheumatoid arthritis pain, dysfunction, and progression, “the standard of care would be a tumor necrosis factor [TNF] inhibitor as the active comparator,” said Dr. Juche, a rheumatologist at Johanniter Hospital in Treuenbrietzen, Germany. Because TNF inhibitors are so effective, a study that uses this treatment in the comparator arm would likely have to be a noninferiority study and would also probably have to involve a relatively large number of patients, he said in an interview.

The standard approach for drug-trial design in patients with RA in recent years has been to follow a model that's more than a decade old, dating back to the first studies on TNF inhibitors during the 1990s: “Patients who did not adequately respond to immunosuppressive drugs were randomly assigned to either an experimental condition under which they received the new substance, or to a control condition under which they continued their formerly inefficient treatment and received a placebo.”

To more systematically assess the scope of the problem, he and his associate reviewed 17 recent, published clinical trials that drug companies used to document the safety and efficacy of three new drugs, abatacept, golimumab, and tocilizumab, to the European Medicines Agencies. Dr. Juche said these studies fairly represented most recently performed drug efficacy trials for patients with RA.

Of the seven studies he reviewed that tested abatacept, none used a control therapy that effectively treated the patients' disease. In all seven studies, patients remained on treatment with a disease-modifying antirheumatic drug (DMARD) that they had already failed on, most commonly methotrexate. During these studies, “patients experienced a persistent, high disease activity,” he reported.

Among four pivotal studies involving golimumab, one enrolled methotrexate-naive patients and then used methotrexate as the control drug. The other three used control groups that received placebo and nothing else or placebo plus methotrexate for enrolled patients who had already failed methotrexate.

A similar pattern existed for the six studies of tocilizumab that Dr. Juche reviewed.

One of the six used methotrexate as the comparator in a trial that enrolled methotrexate-naive patients. The other five studies used comparator groups on either placebo alone or placebo plus a DMARD to which the patient had already not responded.

Dr. Juche added that rheumatology is not unique in having so many of its trials involve ineffective regimens in the control groups.

New drugs should be compared with a TNF inhibitor, suggested Dr. Aaron Juche.

Source Mitchel L. Zoler/Elsevier Global Medical News

Major Finding: At 3 days after a single drug dose, gouty arthritis patients who were treated with canakinumab had a statistically significant, average reduction of 11 mm on their pain score, compared with patients who were treated with triamcinolone acetonide (on a 0- to 100-mm visual analog scale). After 12 weeks on randomized treatment, patients treated with canakinumab had a statistically significant 55%–68% relative decrease in new-flare frequency, compared with triamcinolone acetonide–treated patients.

Data Source: The Beta-RELIEVED and Beta-RELIEVED II trials, two identically designed studies that together randomized 456 patients with recent flares of gouty arthritis who were contraindicated for, intolerant of, or unresponsive to NSAIDs and colchicine to treatment with canakinumab or triamcinolone acetonide.

Disclosures: The beta-RELIEVED trials were sponsored by Novartis, which markets canakinumab (Ilaris). Dr. Schlesinger said that she is on the advisory board of Novartis, Enzyme Rx, Takeda, URL Pharma, and Savient. She is a consultant to and has received research grants from Novartis, and is on the speakers bureau of Takeda and Savient. Dr. So said that he is a consultant to Novartis, Bristol-Myers Squibb, Merck, Pfizer, and UCB Pharma. Dr. Khanna said that he is a consultant to Novartis, Takeda, Savient, and UCB Pharma.

LONDON – Use of canakinumab led to greater reductions in pain among patients with acute gouty arthritis flares after 3 days, and superior prevention of new flares during 12 weeks of follow-up, compared with triamcinolone acetonide in a pair of phase III trials that together enrolled 456 patients.

“Canakinumab is a potential new therapeutic option for acute flares in frequently flaring gouty arthritis patients with limited treatment options,” Dr. Naomi Schlesinger said at the meeting.

Canakinumab is a fully human monoclonal antibody to interleukin (IL)-1 beta that selectively binds to and inhibits the proinflammatory molecule IL-1 beta, and already has Food and Drug Administration approval for treating CAPS (cryopyrin-associated periodic syndromes).

Based in part on the efficacy and safety data from the two reported phase III trials, Novartis, the company that markets canakinumab (Ilaris), filed an application with the FDA earlier this year for a supplemental indication for treating gouty arthritis flares. The FDA's Arthritis Advisory Committee discussed this application on June 21.

In the two new gouty arthritis trials, canakinumab's safety profile during the first 12 weeks of treatment “appeared consistent with longer-term safety data from CAPS patients; there were no safety signals related to specific organ class,” said Dr. Schlesinger, chief of the division of rheumatology and connective tissue research at the Robert Wood Johnson Medical School in New Brunswick, N.J. The most notable safety observation she made from the new results centered on “a modest increase in infections, mostly mild to moderate, with no opportunistic infections reported,” she said.

Despite this promising safety and efficacy, one expert viewed canakinumab as an agent for a “niche population, patients [with gout] who flare and you can't do anything about it” using standard drugs, commented Dr. Dinesh Khanna, a rheumatologist specializing in gout at the University of California, Los Angeles.

Goutologists see a lot of patients with diabetes, kidney disease, and hypertension who can't take NSAIDs or colchicine. “You also can't give them a steroid monthly, so these patients flare because of their high uric acid level and you're stuck. These are the patients who can be treated with an anti-IL-1 beta to prevent gout attacks,” he said in an interview.

The Beta-RELIEVED (Response in Acute Flare and in Prevention of Episodes of Reflare in Gout) and Beta-RELIEVED II trials enrolled patients within 5 days of an acute flare of gouty arthritis who had at least three flares during the prior year and were contraindicated for, intolerant of, or unresponsive to NSAIDs and colchicine. All patients met the American College of Rheumatology's diagnostic criteria for gouty arthritis, and had pain intensity of at least 50 mm on a visual analog scale of 0–100 mm.

The researchers randomized patients to receive a subcutaneous injection of 150 mg canakinumab or an intramuscular injection of 40 mg triamcinolone acetonide. Patients who reflared during the subsequent 12 weeks during the first phase of the study qualified to receive an additional dose of their assigned drug with each flare.

One of the study's two primary end points was pain resolution at 72 hours after initial treatment. At that time, patients treated with canakinumab in the Beta-RELIEVED study had an average pain score that was 11 mm lower than that of patients in the comparator group, a statistically significant difference, reported Dr. Alexander So, a study coinvestigator and professor of rheumatology at the University of Lausanne (Switzerland).

Patients who were treated with canakinumab began to show significantly better pain reduction, compared with those who got triamcinolone within 12 hours after their first dose, and the advantage in pain relief continued each time the investigators measured pain during the first 7 days after treatment, Dr. So said. Neither Dr. So nor Dr. Schlesinger reported the results for this end point from the Beta-RELIEVED II trial.

The second primary end point was the percentage of patients having new flares during the first 12 weeks following their initial therapy. In the Beta-RELIEVED trial, 19% of the 115 patients who were treated with canakinumab and 37% of the 115 patients treated with triamcinolone had a new flare, a 55% relative risk reduction with canakinumab that was statistically significant. In the second trial, canakinumab use led to a 68% relative reduction in new flares, also a statistically significant difference in the study that randomized 226 patients, Dr. Schlesinger reported.

The canakinumab-treated patients also showed other signs of superior response in several secondary efficacy measures. Patients in the canakinumab group had a significant reduction in their mean number of flares, significantly less inflammation and swelling, and better suppression of inflammatory markers after 12 weeks, the researchers said.

In the safety analysis, canakinumab was associated with similar rates of all adverse events, a similar low rate of serious adverse events, and a similar low rate of adverse events leading to discontinuation, compared with patients who received triamcinolone.

Major Finding: At 3 days after a single drug dose, gouty arthritis patients who were treated with canakinumab had a statistically significant, average reduction of 11 mm on their pain score, compared with patients who were treated with triamcinolone acetonide (on a 0- to 100-mm visual analog scale). After 12 weeks on randomized treatment, patients treated with canakinumab had a statistically significant 55%–68% relative decrease in new-flare frequency, compared with triamcinolone acetonide–treated patients.

Data Source: The Beta-RELIEVED and Beta-RELIEVED II trials, two identically designed studies that together randomized 456 patients with recent flares of gouty arthritis who were contraindicated for, intolerant of, or unresponsive to NSAIDs and colchicine to treatment with canakinumab or triamcinolone acetonide.

Disclosures: The beta-RELIEVED trials were sponsored by Novartis, which markets canakinumab (Ilaris). Dr. Schlesinger said that she is on the advisory board of Novartis, Enzyme Rx, Takeda, URL Pharma, and Savient. She is a consultant to and has received research grants from Novartis, and is on the speakers bureau of Takeda and Savient. Dr. So said that he is a consultant to Novartis, Bristol-Myers Squibb, Merck, Pfizer, and UCB Pharma. Dr. Khanna said that he is a consultant to Novartis, Takeda, Savient, and UCB Pharma.

LONDON – Use of canakinumab led to greater reductions in pain among patients with acute gouty arthritis flares after 3 days, and superior prevention of new flares during 12 weeks of follow-up, compared with triamcinolone acetonide in a pair of phase III trials that together enrolled 456 patients.

“Canakinumab is a potential new therapeutic option for acute flares in frequently flaring gouty arthritis patients with limited treatment options,” Dr. Naomi Schlesinger said at the meeting.

Canakinumab is a fully human monoclonal antibody to interleukin (IL)-1 beta that selectively binds to and inhibits the proinflammatory molecule IL-1 beta, and already has Food and Drug Administration approval for treating CAPS (cryopyrin-associated periodic syndromes).

Based in part on the efficacy and safety data from the two reported phase III trials, Novartis, the company that markets canakinumab (Ilaris), filed an application with the FDA earlier this year for a supplemental indication for treating gouty arthritis flares. The FDA's Arthritis Advisory Committee discussed this application on June 21.

In the two new gouty arthritis trials, canakinumab's safety profile during the first 12 weeks of treatment “appeared consistent with longer-term safety data from CAPS patients; there were no safety signals related to specific organ class,” said Dr. Schlesinger, chief of the division of rheumatology and connective tissue research at the Robert Wood Johnson Medical School in New Brunswick, N.J. The most notable safety observation she made from the new results centered on “a modest increase in infections, mostly mild to moderate, with no opportunistic infections reported,” she said.

Despite this promising safety and efficacy, one expert viewed canakinumab as an agent for a “niche population, patients [with gout] who flare and you can't do anything about it” using standard drugs, commented Dr. Dinesh Khanna, a rheumatologist specializing in gout at the University of California, Los Angeles.

Goutologists see a lot of patients with diabetes, kidney disease, and hypertension who can't take NSAIDs or colchicine. “You also can't give them a steroid monthly, so these patients flare because of their high uric acid level and you're stuck. These are the patients who can be treated with an anti-IL-1 beta to prevent gout attacks,” he said in an interview.

The Beta-RELIEVED (Response in Acute Flare and in Prevention of Episodes of Reflare in Gout) and Beta-RELIEVED II trials enrolled patients within 5 days of an acute flare of gouty arthritis who had at least three flares during the prior year and were contraindicated for, intolerant of, or unresponsive to NSAIDs and colchicine. All patients met the American College of Rheumatology's diagnostic criteria for gouty arthritis, and had pain intensity of at least 50 mm on a visual analog scale of 0–100 mm.

The researchers randomized patients to receive a subcutaneous injection of 150 mg canakinumab or an intramuscular injection of 40 mg triamcinolone acetonide. Patients who reflared during the subsequent 12 weeks during the first phase of the study qualified to receive an additional dose of their assigned drug with each flare.

One of the study's two primary end points was pain resolution at 72 hours after initial treatment. At that time, patients treated with canakinumab in the Beta-RELIEVED study had an average pain score that was 11 mm lower than that of patients in the comparator group, a statistically significant difference, reported Dr. Alexander So, a study coinvestigator and professor of rheumatology at the University of Lausanne (Switzerland).

Patients who were treated with canakinumab began to show significantly better pain reduction, compared with those who got triamcinolone within 12 hours after their first dose, and the advantage in pain relief continued each time the investigators measured pain during the first 7 days after treatment, Dr. So said. Neither Dr. So nor Dr. Schlesinger reported the results for this end point from the Beta-RELIEVED II trial.

The second primary end point was the percentage of patients having new flares during the first 12 weeks following their initial therapy. In the Beta-RELIEVED trial, 19% of the 115 patients who were treated with canakinumab and 37% of the 115 patients treated with triamcinolone had a new flare, a 55% relative risk reduction with canakinumab that was statistically significant. In the second trial, canakinumab use led to a 68% relative reduction in new flares, also a statistically significant difference in the study that randomized 226 patients, Dr. Schlesinger reported.

The canakinumab-treated patients also showed other signs of superior response in several secondary efficacy measures. Patients in the canakinumab group had a significant reduction in their mean number of flares, significantly less inflammation and swelling, and better suppression of inflammatory markers after 12 weeks, the researchers said.

In the safety analysis, canakinumab was associated with similar rates of all adverse events, a similar low rate of serious adverse events, and a similar low rate of adverse events leading to discontinuation, compared with patients who received triamcinolone.

Major Finding: At 3 days after a single drug dose, gouty arthritis patients who were treated with canakinumab had a statistically significant, average reduction of 11 mm on their pain score, compared with patients who were treated with triamcinolone acetonide (on a 0- to 100-mm visual analog scale). After 12 weeks on randomized treatment, patients treated with canakinumab had a statistically significant 55%–68% relative decrease in new-flare frequency, compared with triamcinolone acetonide–treated patients.

Data Source: The Beta-RELIEVED and Beta-RELIEVED II trials, two identically designed studies that together randomized 456 patients with recent flares of gouty arthritis who were contraindicated for, intolerant of, or unresponsive to NSAIDs and colchicine to treatment with canakinumab or triamcinolone acetonide.

Disclosures: The beta-RELIEVED trials were sponsored by Novartis, which markets canakinumab (Ilaris). Dr. Schlesinger said that she is on the advisory board of Novartis, Enzyme Rx, Takeda, URL Pharma, and Savient. She is a consultant to and has received research grants from Novartis, and is on the speakers bureau of Takeda and Savient. Dr. So said that he is a consultant to Novartis, Bristol-Myers Squibb, Merck, Pfizer, and UCB Pharma. Dr. Khanna said that he is a consultant to Novartis, Takeda, Savient, and UCB Pharma.

LONDON – Use of canakinumab led to greater reductions in pain among patients with acute gouty arthritis flares after 3 days, and superior prevention of new flares during 12 weeks of follow-up, compared with triamcinolone acetonide in a pair of phase III trials that together enrolled 456 patients.

“Canakinumab is a potential new therapeutic option for acute flares in frequently flaring gouty arthritis patients with limited treatment options,” Dr. Naomi Schlesinger said at the meeting.

Canakinumab is a fully human monoclonal antibody to interleukin (IL)-1 beta that selectively binds to and inhibits the proinflammatory molecule IL-1 beta, and already has Food and Drug Administration approval for treating CAPS (cryopyrin-associated periodic syndromes).

Based in part on the efficacy and safety data from the two reported phase III trials, Novartis, the company that markets canakinumab (Ilaris), filed an application with the FDA earlier this year for a supplemental indication for treating gouty arthritis flares. The FDA's Arthritis Advisory Committee discussed this application on June 21.

In the two new gouty arthritis trials, canakinumab's safety profile during the first 12 weeks of treatment “appeared consistent with longer-term safety data from CAPS patients; there were no safety signals related to specific organ class,” said Dr. Schlesinger, chief of the division of rheumatology and connective tissue research at the Robert Wood Johnson Medical School in New Brunswick, N.J. The most notable safety observation she made from the new results centered on “a modest increase in infections, mostly mild to moderate, with no opportunistic infections reported,” she said.

Despite this promising safety and efficacy, one expert viewed canakinumab as an agent for a “niche population, patients [with gout] who flare and you can't do anything about it” using standard drugs, commented Dr. Dinesh Khanna, a rheumatologist specializing in gout at the University of California, Los Angeles.

Goutologists see a lot of patients with diabetes, kidney disease, and hypertension who can't take NSAIDs or colchicine. “You also can't give them a steroid monthly, so these patients flare because of their high uric acid level and you're stuck. These are the patients who can be treated with an anti-IL-1 beta to prevent gout attacks,” he said in an interview.

The Beta-RELIEVED (Response in Acute Flare and in Prevention of Episodes of Reflare in Gout) and Beta-RELIEVED II trials enrolled patients within 5 days of an acute flare of gouty arthritis who had at least three flares during the prior year and were contraindicated for, intolerant of, or unresponsive to NSAIDs and colchicine. All patients met the American College of Rheumatology's diagnostic criteria for gouty arthritis, and had pain intensity of at least 50 mm on a visual analog scale of 0–100 mm.

The researchers randomized patients to receive a subcutaneous injection of 150 mg canakinumab or an intramuscular injection of 40 mg triamcinolone acetonide. Patients who reflared during the subsequent 12 weeks during the first phase of the study qualified to receive an additional dose of their assigned drug with each flare.

One of the study's two primary end points was pain resolution at 72 hours after initial treatment. At that time, patients treated with canakinumab in the Beta-RELIEVED study had an average pain score that was 11 mm lower than that of patients in the comparator group, a statistically significant difference, reported Dr. Alexander So, a study coinvestigator and professor of rheumatology at the University of Lausanne (Switzerland).

Patients who were treated with canakinumab began to show significantly better pain reduction, compared with those who got triamcinolone within 12 hours after their first dose, and the advantage in pain relief continued each time the investigators measured pain during the first 7 days after treatment, Dr. So said. Neither Dr. So nor Dr. Schlesinger reported the results for this end point from the Beta-RELIEVED II trial.

The second primary end point was the percentage of patients having new flares during the first 12 weeks following their initial therapy. In the Beta-RELIEVED trial, 19% of the 115 patients who were treated with canakinumab and 37% of the 115 patients treated with triamcinolone had a new flare, a 55% relative risk reduction with canakinumab that was statistically significant. In the second trial, canakinumab use led to a 68% relative reduction in new flares, also a statistically significant difference in the study that randomized 226 patients, Dr. Schlesinger reported.

The canakinumab-treated patients also showed other signs of superior response in several secondary efficacy measures. Patients in the canakinumab group had a significant reduction in their mean number of flares, significantly less inflammation and swelling, and better suppression of inflammatory markers after 12 weeks, the researchers said.

In the safety analysis, canakinumab was associated with similar rates of all adverse events, a similar low rate of serious adverse events, and a similar low rate of adverse events leading to discontinuation, compared with patients who received triamcinolone.

Major Finding: In 2009, U.S. patients who underwent first-time, isolated CABG surgery had a 1.9% perioperative mortality rate and a 1.2% stroke rate, significant declines compared with the 2.4% mortality rate and 1.6% stroke rate during 2000.

Data Source: Review of records for 1.4 million U.S. patients in the Society of Thoracic Surgeons' national adult cardiac surgery database.

Disclosures: Dr. ElBardissi and Dr. Ferguson said they had no disclosures.

PHILADELPHIA – U.S. cardiac surgeons increasingly performed coronary artery bypass surgery on more complex patients during 2000-2009, yet significant drops in the rates of perioperative deaths and strokes were seen during those years, according to a review of more than 1.4 million procedures.

“The major implication of this study is that we are operating on a more complex cohort of patients, and we're doing a better job, with less death and stroke than [was the case] not too long ago. This has implications for how we stratify patients for revascularization therapy,” said Dr. Andrew W. ElBardissi at the meeting.

“Many of the patterns we are seeing reflect the results from some of the more rigorous prospective studies that have dictated practice. … Not only have outcomes improved [as a result], but we seem to be operating on the correct cohort of patients,” said Dr. ElBardissi, a cardiac surgeon at Brigham and Women's Hospital in Boston.

Dr. T. Bruce Ferguson Jr. concurred. “This study clearly documented continued improvement in CABG, particularly in the CABG-PCI era of the last decade. These are clearly more technically difficult operations,” said Dr. Ferguson, professor of surgery and chairman of cardiovascular sciences at East Carolina University in Greenville, N.C.

Dr. ElBardissi's analysis used data collected on more than 1.4 million patients who underwent first-time, isolated CABG at a hospital participating in the Society of Thoracic Surgeons' adult cardiac surgery database. The data he presented compared 136,513 patients who underwent CABG in 2000 with 160,905 patients who had this surgery in 2009.

Major shifts during those years included a statistically significant drop in the prevalence of recent smoking (from 60% in 2000 to 30% in 2009), but significant increases in the prevalence of patients with hypercholesterolemia (84% in 2009 vs. 60% in 2000), hypertension (85% vs. 71%), and chronic obstructive pulmonary disease (23% vs. 16%). The percentage of patients who were previously treated by PCI also jumped to 26% in 2009, from 19% in 2000.

Significant rises in the rate of preoperative treatment with cardioprotective drugs were also seen, notably in the use of aspirin, beta-blockers, ACE inhibitors, and statins. Beta-blocker use jumped from 61% of patients in 2000 to 81% in 2009.

The prevalence of left main coronary artery stenosis rose from 23% of patients in 2000 to 32% in 2009.

The statistics also documented meaningful changes in how CABG occurred. Use of an internal mammary artery graft rose from 84% of cases in 2000 to 95% in 2009, and off-pump surgery increased from 14% of cases to 21%.

Elective procedures dropped from 58% in 2000 to 41% in 2009. The largest subgroup of patients shifted to urgent cases, which rose from 38% of patients in 2000 to 54% in 2009.

Mortality during 30-day follow-up fell significantly, from 2.4% in 2000 to 1.9% in 2009 – a 24% risk-adjusted relative rate reduction. In elective and urgent cases, 30-day mortality fell from 2.1% to 1.6%.

Stroke at 30 days dropped significantly, from 1.6% in 2000 to 1.2% in 2009. In elective and urgent cases, the rate declined from 1.6% to 1.1%.

The 30-day results also showed significant declines in deep sternal wound rates (from 0.55% in 2000 to 0.37% in 2009), and in the need for reoperations because of bleeding (2.5% vs. 2.2%).

Major Finding: In 2009, U.S. patients who underwent first-time, isolated CABG surgery had a 1.9% perioperative mortality rate and a 1.2% stroke rate, significant declines compared with the 2.4% mortality rate and 1.6% stroke rate during 2000.

Data Source: Review of records for 1.4 million U.S. patients in the Society of Thoracic Surgeons' national adult cardiac surgery database.

Disclosures: Dr. ElBardissi and Dr. Ferguson said they had no disclosures.

PHILADELPHIA – U.S. cardiac surgeons increasingly performed coronary artery bypass surgery on more complex patients during 2000-2009, yet significant drops in the rates of perioperative deaths and strokes were seen during those years, according to a review of more than 1.4 million procedures.

“The major implication of this study is that we are operating on a more complex cohort of patients, and we're doing a better job, with less death and stroke than [was the case] not too long ago. This has implications for how we stratify patients for revascularization therapy,” said Dr. Andrew W. ElBardissi at the meeting.

“Many of the patterns we are seeing reflect the results from some of the more rigorous prospective studies that have dictated practice. … Not only have outcomes improved [as a result], but we seem to be operating on the correct cohort of patients,” said Dr. ElBardissi, a cardiac surgeon at Brigham and Women's Hospital in Boston.

Dr. T. Bruce Ferguson Jr. concurred. “This study clearly documented continued improvement in CABG, particularly in the CABG-PCI era of the last decade. These are clearly more technically difficult operations,” said Dr. Ferguson, professor of surgery and chairman of cardiovascular sciences at East Carolina University in Greenville, N.C.

Dr. ElBardissi's analysis used data collected on more than 1.4 million patients who underwent first-time, isolated CABG at a hospital participating in the Society of Thoracic Surgeons' adult cardiac surgery database. The data he presented compared 136,513 patients who underwent CABG in 2000 with 160,905 patients who had this surgery in 2009.

Major shifts during those years included a statistically significant drop in the prevalence of recent smoking (from 60% in 2000 to 30% in 2009), but significant increases in the prevalence of patients with hypercholesterolemia (84% in 2009 vs. 60% in 2000), hypertension (85% vs. 71%), and chronic obstructive pulmonary disease (23% vs. 16%). The percentage of patients who were previously treated by PCI also jumped to 26% in 2009, from 19% in 2000.

Significant rises in the rate of preoperative treatment with cardioprotective drugs were also seen, notably in the use of aspirin, beta-blockers, ACE inhibitors, and statins. Beta-blocker use jumped from 61% of patients in 2000 to 81% in 2009.

The prevalence of left main coronary artery stenosis rose from 23% of patients in 2000 to 32% in 2009.

The statistics also documented meaningful changes in how CABG occurred. Use of an internal mammary artery graft rose from 84% of cases in 2000 to 95% in 2009, and off-pump surgery increased from 14% of cases to 21%.

Elective procedures dropped from 58% in 2000 to 41% in 2009. The largest subgroup of patients shifted to urgent cases, which rose from 38% of patients in 2000 to 54% in 2009.

Mortality during 30-day follow-up fell significantly, from 2.4% in 2000 to 1.9% in 2009 – a 24% risk-adjusted relative rate reduction. In elective and urgent cases, 30-day mortality fell from 2.1% to 1.6%.

Stroke at 30 days dropped significantly, from 1.6% in 2000 to 1.2% in 2009. In elective and urgent cases, the rate declined from 1.6% to 1.1%.

The 30-day results also showed significant declines in deep sternal wound rates (from 0.55% in 2000 to 0.37% in 2009), and in the need for reoperations because of bleeding (2.5% vs. 2.2%).

Major Finding: In 2009, U.S. patients who underwent first-time, isolated CABG surgery had a 1.9% perioperative mortality rate and a 1.2% stroke rate, significant declines compared with the 2.4% mortality rate and 1.6% stroke rate during 2000.

Data Source: Review of records for 1.4 million U.S. patients in the Society of Thoracic Surgeons' national adult cardiac surgery database.

Disclosures: Dr. ElBardissi and Dr. Ferguson said they had no disclosures.

PHILADELPHIA – U.S. cardiac surgeons increasingly performed coronary artery bypass surgery on more complex patients during 2000-2009, yet significant drops in the rates of perioperative deaths and strokes were seen during those years, according to a review of more than 1.4 million procedures.

“The major implication of this study is that we are operating on a more complex cohort of patients, and we're doing a better job, with less death and stroke than [was the case] not too long ago. This has implications for how we stratify patients for revascularization therapy,” said Dr. Andrew W. ElBardissi at the meeting.

“Many of the patterns we are seeing reflect the results from some of the more rigorous prospective studies that have dictated practice. … Not only have outcomes improved [as a result], but we seem to be operating on the correct cohort of patients,” said Dr. ElBardissi, a cardiac surgeon at Brigham and Women's Hospital in Boston.

Dr. T. Bruce Ferguson Jr. concurred. “This study clearly documented continued improvement in CABG, particularly in the CABG-PCI era of the last decade. These are clearly more technically difficult operations,” said Dr. Ferguson, professor of surgery and chairman of cardiovascular sciences at East Carolina University in Greenville, N.C.

Dr. ElBardissi's analysis used data collected on more than 1.4 million patients who underwent first-time, isolated CABG at a hospital participating in the Society of Thoracic Surgeons' adult cardiac surgery database. The data he presented compared 136,513 patients who underwent CABG in 2000 with 160,905 patients who had this surgery in 2009.

Major shifts during those years included a statistically significant drop in the prevalence of recent smoking (from 60% in 2000 to 30% in 2009), but significant increases in the prevalence of patients with hypercholesterolemia (84% in 2009 vs. 60% in 2000), hypertension (85% vs. 71%), and chronic obstructive pulmonary disease (23% vs. 16%). The percentage of patients who were previously treated by PCI also jumped to 26% in 2009, from 19% in 2000.

Significant rises in the rate of preoperative treatment with cardioprotective drugs were also seen, notably in the use of aspirin, beta-blockers, ACE inhibitors, and statins. Beta-blocker use jumped from 61% of patients in 2000 to 81% in 2009.

The prevalence of left main coronary artery stenosis rose from 23% of patients in 2000 to 32% in 2009.

The statistics also documented meaningful changes in how CABG occurred. Use of an internal mammary artery graft rose from 84% of cases in 2000 to 95% in 2009, and off-pump surgery increased from 14% of cases to 21%.

Elective procedures dropped from 58% in 2000 to 41% in 2009. The largest subgroup of patients shifted to urgent cases, which rose from 38% of patients in 2000 to 54% in 2009.

Mortality during 30-day follow-up fell significantly, from 2.4% in 2000 to 1.9% in 2009 – a 24% risk-adjusted relative rate reduction. In elective and urgent cases, 30-day mortality fell from 2.1% to 1.6%.

Stroke at 30 days dropped significantly, from 1.6% in 2000 to 1.2% in 2009. In elective and urgent cases, the rate declined from 1.6% to 1.1%.

The 30-day results also showed significant declines in deep sternal wound rates (from 0.55% in 2000 to 0.37% in 2009), and in the need for reoperations because of bleeding (2.5% vs. 2.2%).