Bruce Jancin

GOTHENBURG, SWEDEN – Onychomycosis remains a difficult disorder to treat and cure, even with modern antifungal agents. But the chances of success can be greatly enhanced through application of several proven, evidence-based strategies.

A recent study identified multiple baseline factors associated with a low cure rate following a standard 3-month course of oral terbinafine for onychomycosis. One preemptive strategy in patients possessing several of these poor-prognosis factors is to consider combination therapy from the outset. Alternatively, the standard 3 months of terbinafine could be stretched for 5-6 months, Dr. Bardur Sigurgeirsson said at the meeting.

The host-related prognostic factors were identified in Dr. Sigurgeirsson's recent secondary retrospective analysis of 3-year outcomes in 199 Icelandic participants in a large international randomized trial of continuous versus intermittent terbinafine (J. Eur. Acad. Dermatol. Venereol. 2010;24:679-84).

Several of the prognostic factors were already known, but the study provided the first-ever supporting data validating their legitimacy, said Dr. Sigurgeirsson of the University of Iceland, Reykjavik.

In the multivariate, logistic, regression analysis, baseline factors associated with a negative outcome at 72 weeks of follow-up – that is, failure to achieve mycologic or clinical cure – included matrix involvement, lateral nail edge involvement, and dermatophytoma. Slow nail growth from screening to baseline was another predictor of lack of cure; this makes sense, as patients with faster-growing nails are likely to shed the infected part sooner, he noted.

Other factors enabling physicians to select good candidates for up-front combination or extended therapy were being over age 65 years, being male, having a history of prior fungal toe infection, and having a positive culture at 24 weeks' follow-up, even if the nails look good at that point.

Several factors in popular dermatologic lore to predict poor outcome were not borne out in the study. The extent of infection involvement, the number of infected toenails, duration of infection, and presence of spikes were unrelated to the 72-week cure rate. The greatest likelihood of cure at 72 weeks' follow-up after the standard 3 months of oral terbinafine was seen in younger female patients with fast nail growth.

An earlier, randomized, multicenter study by Dr. Sigurgeirsson and coworkers made the case for up-front combination therapy with amorolfine hydrochloride 5% nail lacquer and oral terbinafine for treating onychomycosis in patients with terbinafine monotherapy lack-of-cure risk factors. The trial involved 249 patients; one of the strongest predictors of poor outcome was baseline nail matrix involvement. The success rate at 18 months was 59% for combination therapy, compared with 45% for oral terbinafine monotherapy. The cost per cure was significantly less with combination therapy (Br. J. Dermatol. 2007;157:149-57).

Onychomycosis is best viewed as a chronic relapsing condition, as evidenced by a 5-year, blinded, prospective follow-up study Dr. Sigurgeirsson and colleagues conducted in terbinafine- or itraconazole-treated patients (Arch. Dermatol. 2002;138:353-7). The mycologic relapse rates were 53% in the itraconazole arm and 48% with terbinafine.

In a subsequent study of nearly 4,000 patients, the investigators identified a number of risk factors for recurrent onychomycosis: cancer, 3.4-fold increased risk; psoriasis, 2.4-fold increased risk; tinea pedis interdigitalis, 3.9-fold increased risk; moccasin form of tinea pedis, 4.3-fold increased risk; and having a spouse, parents, or children with onychomycosis, 2.5- to 3.5-fold increased risk (J. Eur. Acad. Dermatol. Venereol. 2004;18:48-51).

Prophylactic therapy is worth considering following cure of onychomycosis in patients at increased risk for relapse based upon their risk factor profile, Dr. Sigurgeirsson said. He and his coworkers recently showed that amorolfine nail lacquer applied once every 2 weeks is safe and effective for this purpose (J. Eur. Acad. Dermatol. Venereol. 2010;24:910-5).

Many of his studies of terbinafine for onychomycosis were supported by research grants from Novartis.

Vitals

White superficial onychomycosis is seen on the surface of the toenails.

Source ©2005 Elsevier Inc.

GOTHENBURG, SWEDEN – Onychomycosis remains a difficult disorder to treat and cure, even with modern antifungal agents. But the chances of success can be greatly enhanced through application of several proven, evidence-based strategies.

A recent study identified multiple baseline factors associated with a low cure rate following a standard 3-month course of oral terbinafine for onychomycosis. One preemptive strategy in patients possessing several of these poor-prognosis factors is to consider combination therapy from the outset. Alternatively, the standard 3 months of terbinafine could be stretched for 5-6 months, Dr. Bardur Sigurgeirsson said at the meeting.

The host-related prognostic factors were identified in Dr. Sigurgeirsson's recent secondary retrospective analysis of 3-year outcomes in 199 Icelandic participants in a large international randomized trial of continuous versus intermittent terbinafine (J. Eur. Acad. Dermatol. Venereol. 2010;24:679-84).

Several of the prognostic factors were already known, but the study provided the first-ever supporting data validating their legitimacy, said Dr. Sigurgeirsson of the University of Iceland, Reykjavik.

In the multivariate, logistic, regression analysis, baseline factors associated with a negative outcome at 72 weeks of follow-up – that is, failure to achieve mycologic or clinical cure – included matrix involvement, lateral nail edge involvement, and dermatophytoma. Slow nail growth from screening to baseline was another predictor of lack of cure; this makes sense, as patients with faster-growing nails are likely to shed the infected part sooner, he noted.

Other factors enabling physicians to select good candidates for up-front combination or extended therapy were being over age 65 years, being male, having a history of prior fungal toe infection, and having a positive culture at 24 weeks' follow-up, even if the nails look good at that point.

Several factors in popular dermatologic lore to predict poor outcome were not borne out in the study. The extent of infection involvement, the number of infected toenails, duration of infection, and presence of spikes were unrelated to the 72-week cure rate. The greatest likelihood of cure at 72 weeks' follow-up after the standard 3 months of oral terbinafine was seen in younger female patients with fast nail growth.

An earlier, randomized, multicenter study by Dr. Sigurgeirsson and coworkers made the case for up-front combination therapy with amorolfine hydrochloride 5% nail lacquer and oral terbinafine for treating onychomycosis in patients with terbinafine monotherapy lack-of-cure risk factors. The trial involved 249 patients; one of the strongest predictors of poor outcome was baseline nail matrix involvement. The success rate at 18 months was 59% for combination therapy, compared with 45% for oral terbinafine monotherapy. The cost per cure was significantly less with combination therapy (Br. J. Dermatol. 2007;157:149-57).

Onychomycosis is best viewed as a chronic relapsing condition, as evidenced by a 5-year, blinded, prospective follow-up study Dr. Sigurgeirsson and colleagues conducted in terbinafine- or itraconazole-treated patients (Arch. Dermatol. 2002;138:353-7). The mycologic relapse rates were 53% in the itraconazole arm and 48% with terbinafine.

In a subsequent study of nearly 4,000 patients, the investigators identified a number of risk factors for recurrent onychomycosis: cancer, 3.4-fold increased risk; psoriasis, 2.4-fold increased risk; tinea pedis interdigitalis, 3.9-fold increased risk; moccasin form of tinea pedis, 4.3-fold increased risk; and having a spouse, parents, or children with onychomycosis, 2.5- to 3.5-fold increased risk (J. Eur. Acad. Dermatol. Venereol. 2004;18:48-51).

Prophylactic therapy is worth considering following cure of onychomycosis in patients at increased risk for relapse based upon their risk factor profile, Dr. Sigurgeirsson said. He and his coworkers recently showed that amorolfine nail lacquer applied once every 2 weeks is safe and effective for this purpose (J. Eur. Acad. Dermatol. Venereol. 2010;24:910-5).

Many of his studies of terbinafine for onychomycosis were supported by research grants from Novartis.

Vitals

White superficial onychomycosis is seen on the surface of the toenails.

Source ©2005 Elsevier Inc.

GOTHENBURG, SWEDEN – Onychomycosis remains a difficult disorder to treat and cure, even with modern antifungal agents. But the chances of success can be greatly enhanced through application of several proven, evidence-based strategies.

A recent study identified multiple baseline factors associated with a low cure rate following a standard 3-month course of oral terbinafine for onychomycosis. One preemptive strategy in patients possessing several of these poor-prognosis factors is to consider combination therapy from the outset. Alternatively, the standard 3 months of terbinafine could be stretched for 5-6 months, Dr. Bardur Sigurgeirsson said at the meeting.

The host-related prognostic factors were identified in Dr. Sigurgeirsson's recent secondary retrospective analysis of 3-year outcomes in 199 Icelandic participants in a large international randomized trial of continuous versus intermittent terbinafine (J. Eur. Acad. Dermatol. Venereol. 2010;24:679-84).

Several of the prognostic factors were already known, but the study provided the first-ever supporting data validating their legitimacy, said Dr. Sigurgeirsson of the University of Iceland, Reykjavik.

In the multivariate, logistic, regression analysis, baseline factors associated with a negative outcome at 72 weeks of follow-up – that is, failure to achieve mycologic or clinical cure – included matrix involvement, lateral nail edge involvement, and dermatophytoma. Slow nail growth from screening to baseline was another predictor of lack of cure; this makes sense, as patients with faster-growing nails are likely to shed the infected part sooner, he noted.

Other factors enabling physicians to select good candidates for up-front combination or extended therapy were being over age 65 years, being male, having a history of prior fungal toe infection, and having a positive culture at 24 weeks' follow-up, even if the nails look good at that point.

Several factors in popular dermatologic lore to predict poor outcome were not borne out in the study. The extent of infection involvement, the number of infected toenails, duration of infection, and presence of spikes were unrelated to the 72-week cure rate. The greatest likelihood of cure at 72 weeks' follow-up after the standard 3 months of oral terbinafine was seen in younger female patients with fast nail growth.

An earlier, randomized, multicenter study by Dr. Sigurgeirsson and coworkers made the case for up-front combination therapy with amorolfine hydrochloride 5% nail lacquer and oral terbinafine for treating onychomycosis in patients with terbinafine monotherapy lack-of-cure risk factors. The trial involved 249 patients; one of the strongest predictors of poor outcome was baseline nail matrix involvement. The success rate at 18 months was 59% for combination therapy, compared with 45% for oral terbinafine monotherapy. The cost per cure was significantly less with combination therapy (Br. J. Dermatol. 2007;157:149-57).

Onychomycosis is best viewed as a chronic relapsing condition, as evidenced by a 5-year, blinded, prospective follow-up study Dr. Sigurgeirsson and colleagues conducted in terbinafine- or itraconazole-treated patients (Arch. Dermatol. 2002;138:353-7). The mycologic relapse rates were 53% in the itraconazole arm and 48% with terbinafine.

In a subsequent study of nearly 4,000 patients, the investigators identified a number of risk factors for recurrent onychomycosis: cancer, 3.4-fold increased risk; psoriasis, 2.4-fold increased risk; tinea pedis interdigitalis, 3.9-fold increased risk; moccasin form of tinea pedis, 4.3-fold increased risk; and having a spouse, parents, or children with onychomycosis, 2.5- to 3.5-fold increased risk (J. Eur. Acad. Dermatol. Venereol. 2004;18:48-51).

Prophylactic therapy is worth considering following cure of onychomycosis in patients at increased risk for relapse based upon their risk factor profile, Dr. Sigurgeirsson said. He and his coworkers recently showed that amorolfine nail lacquer applied once every 2 weeks is safe and effective for this purpose (J. Eur. Acad. Dermatol. Venereol. 2010;24:910-5).

Many of his studies of terbinafine for onychomycosis were supported by research grants from Novartis.

Vitals

White superficial onychomycosis is seen on the surface of the toenails.

Source ©2005 Elsevier Inc.

CHICAGO – Using N-terminal prohormone brain natriuretic peptide levels to guide therapy in patients with systolic heart failure proved superior to standard -of-care management in terms of cardiovascular event rates, quality of life, and echocardiographic parameters in the randomized prospective PROTECT trial.

“If duplicated in larger cohorts, treatment guided by NT-proBNP may represent a new paradigm for heart failure care,” Dr. James L. Januzzi Jr. said at the meeting.

PROTECT (the ProBNP Outpatient Tailored Chronic Heart Failure Therapy study) was a single-center unblinded trial of 151 patients with systolic heart failure and a mean left ventricular ejection fraction of 27%. They were randomized to standard guideline-driven management on the basis of heart failure signs and symptoms or to the same approach with the added goal of reducing NT-proBNP levels to 1,000 pg/mL or less, a threshold previously shown to predict risk in heart failure patients.

Participants were scheduled for quarterly clinic visits, with extra ones as needed to achieve therapeutic goals, said Dr. Januzzi, director of the cardiac intensive care unit at Massachusetts General Hospital, Boston.

The study was halted early for ethical reasons after 10 months. At that point, a total of 100 cardiovascular events – worsening heart failure, heart failure hospitalization, acute coronary syndrome, ventricular arrhythmias, cerebral ischemia, or cardiovascular death – had occurred in the standard-treatment group, compared with 58 events in patients on NT-proBNP–guided therapy

The major difference between the two study arms was the sharply lower likelihood of worsening heart failure or heart failure hospitalization in the NT-proBNP–guided arm.

Importantly, the reduction in cardiovascular events was similar in patients over age 75 and in those who were younger, Dr. Januzzi said.

The secondary outcome of quality of life, assessed using the Minnesota Living with Heart Failure Questionnaire, also showed significantly greater improvement in the guided-treatment arm. In all, 61% of subjects in the NT-proBNP–guided arm achieved at least a 10-point improvement over baseline, considered clinically meaningful, compared with 39% on standard management.

The guided-treatment group also did significantly better in terms of secondary echocardiographic end points, with larger improvements in left ventricular ejection fraction and in ventricular remodeling as reflected by changes in LV end-systolic and end-diastolic volume index, the cardiologist continued.

NT-proBNP–guided therapy proved safe and was well tolerated, with no significant increase in adverse events.

Patients in the guided-treatment arm had a median of six clinic visits, compared with five with standard management. The median baseline NT-proBNP level in the guided-therapy arm was 2,344 pg/mL. It fell to 1,125 pg/mL, with 44% of subjects in the guided-therapy arm attaining an NT-proBNP of 1,000 pg/mL or less.

Session cochair Dr. Gregg C. Fonarow said in an interview that he views PROTECT as a successful proof-of-concept study. But before biomarker-guided treatment of heart failure becomes part of guideline-recommended, routine outpatient care, it will be necessary to see if the Massachusetts General Hospital experience can be extended to other settings, including primary care practices, where many patients with heart failure receive their treatment. This will require a large multicenter trial with a diverse group of clinicians; randomization by site; and hard clinical end points, including mortality.

A proposal for such a study has been presented to the National Heart, Lung, and Blood Institute for funding consideration.

“It's a large and expensive trial, but the impact is potentially profound,” said Dr. Fonarow, professor of medicine and director of the Ahmanson-UCLA Cardiomyopathy Center, Los Angeles. “Given the costs of heart failure and the tremendous number of outpatient visits for this disease, if we truly had a well-validated guide using biomarkers, that would be a phenomenal advance.”

The PROTECT trial was sponsored in part by Roche Diagnostics. Dr. Januzzi declared he serves as a consultant to and speaker for the company.

The NT-proBNP–guided arm had a lower likelihood of worsening heart failure or heart failure hospitalization.

Source DR. JANUZZI

CHICAGO – Using N-terminal prohormone brain natriuretic peptide levels to guide therapy in patients with systolic heart failure proved superior to standard -of-care management in terms of cardiovascular event rates, quality of life, and echocardiographic parameters in the randomized prospective PROTECT trial.

“If duplicated in larger cohorts, treatment guided by NT-proBNP may represent a new paradigm for heart failure care,” Dr. James L. Januzzi Jr. said at the meeting.

PROTECT (the ProBNP Outpatient Tailored Chronic Heart Failure Therapy study) was a single-center unblinded trial of 151 patients with systolic heart failure and a mean left ventricular ejection fraction of 27%. They were randomized to standard guideline-driven management on the basis of heart failure signs and symptoms or to the same approach with the added goal of reducing NT-proBNP levels to 1,000 pg/mL or less, a threshold previously shown to predict risk in heart failure patients.

Participants were scheduled for quarterly clinic visits, with extra ones as needed to achieve therapeutic goals, said Dr. Januzzi, director of the cardiac intensive care unit at Massachusetts General Hospital, Boston.

The study was halted early for ethical reasons after 10 months. At that point, a total of 100 cardiovascular events – worsening heart failure, heart failure hospitalization, acute coronary syndrome, ventricular arrhythmias, cerebral ischemia, or cardiovascular death – had occurred in the standard-treatment group, compared with 58 events in patients on NT-proBNP–guided therapy

The major difference between the two study arms was the sharply lower likelihood of worsening heart failure or heart failure hospitalization in the NT-proBNP–guided arm.

Importantly, the reduction in cardiovascular events was similar in patients over age 75 and in those who were younger, Dr. Januzzi said.

The secondary outcome of quality of life, assessed using the Minnesota Living with Heart Failure Questionnaire, also showed significantly greater improvement in the guided-treatment arm. In all, 61% of subjects in the NT-proBNP–guided arm achieved at least a 10-point improvement over baseline, considered clinically meaningful, compared with 39% on standard management.

The guided-treatment group also did significantly better in terms of secondary echocardiographic end points, with larger improvements in left ventricular ejection fraction and in ventricular remodeling as reflected by changes in LV end-systolic and end-diastolic volume index, the cardiologist continued.

NT-proBNP–guided therapy proved safe and was well tolerated, with no significant increase in adverse events.

Patients in the guided-treatment arm had a median of six clinic visits, compared with five with standard management. The median baseline NT-proBNP level in the guided-therapy arm was 2,344 pg/mL. It fell to 1,125 pg/mL, with 44% of subjects in the guided-therapy arm attaining an NT-proBNP of 1,000 pg/mL or less.

Session cochair Dr. Gregg C. Fonarow said in an interview that he views PROTECT as a successful proof-of-concept study. But before biomarker-guided treatment of heart failure becomes part of guideline-recommended, routine outpatient care, it will be necessary to see if the Massachusetts General Hospital experience can be extended to other settings, including primary care practices, where many patients with heart failure receive their treatment. This will require a large multicenter trial with a diverse group of clinicians; randomization by site; and hard clinical end points, including mortality.

A proposal for such a study has been presented to the National Heart, Lung, and Blood Institute for funding consideration.

“It's a large and expensive trial, but the impact is potentially profound,” said Dr. Fonarow, professor of medicine and director of the Ahmanson-UCLA Cardiomyopathy Center, Los Angeles. “Given the costs of heart failure and the tremendous number of outpatient visits for this disease, if we truly had a well-validated guide using biomarkers, that would be a phenomenal advance.”

The PROTECT trial was sponsored in part by Roche Diagnostics. Dr. Januzzi declared he serves as a consultant to and speaker for the company.

The NT-proBNP–guided arm had a lower likelihood of worsening heart failure or heart failure hospitalization.

Source DR. JANUZZI

CHICAGO – Using N-terminal prohormone brain natriuretic peptide levels to guide therapy in patients with systolic heart failure proved superior to standard -of-care management in terms of cardiovascular event rates, quality of life, and echocardiographic parameters in the randomized prospective PROTECT trial.

“If duplicated in larger cohorts, treatment guided by NT-proBNP may represent a new paradigm for heart failure care,” Dr. James L. Januzzi Jr. said at the meeting.

PROTECT (the ProBNP Outpatient Tailored Chronic Heart Failure Therapy study) was a single-center unblinded trial of 151 patients with systolic heart failure and a mean left ventricular ejection fraction of 27%. They were randomized to standard guideline-driven management on the basis of heart failure signs and symptoms or to the same approach with the added goal of reducing NT-proBNP levels to 1,000 pg/mL or less, a threshold previously shown to predict risk in heart failure patients.

Participants were scheduled for quarterly clinic visits, with extra ones as needed to achieve therapeutic goals, said Dr. Januzzi, director of the cardiac intensive care unit at Massachusetts General Hospital, Boston.

The study was halted early for ethical reasons after 10 months. At that point, a total of 100 cardiovascular events – worsening heart failure, heart failure hospitalization, acute coronary syndrome, ventricular arrhythmias, cerebral ischemia, or cardiovascular death – had occurred in the standard-treatment group, compared with 58 events in patients on NT-proBNP–guided therapy

The major difference between the two study arms was the sharply lower likelihood of worsening heart failure or heart failure hospitalization in the NT-proBNP–guided arm.

Importantly, the reduction in cardiovascular events was similar in patients over age 75 and in those who were younger, Dr. Januzzi said.

The secondary outcome of quality of life, assessed using the Minnesota Living with Heart Failure Questionnaire, also showed significantly greater improvement in the guided-treatment arm. In all, 61% of subjects in the NT-proBNP–guided arm achieved at least a 10-point improvement over baseline, considered clinically meaningful, compared with 39% on standard management.

The guided-treatment group also did significantly better in terms of secondary echocardiographic end points, with larger improvements in left ventricular ejection fraction and in ventricular remodeling as reflected by changes in LV end-systolic and end-diastolic volume index, the cardiologist continued.

NT-proBNP–guided therapy proved safe and was well tolerated, with no significant increase in adverse events.

Patients in the guided-treatment arm had a median of six clinic visits, compared with five with standard management. The median baseline NT-proBNP level in the guided-therapy arm was 2,344 pg/mL. It fell to 1,125 pg/mL, with 44% of subjects in the guided-therapy arm attaining an NT-proBNP of 1,000 pg/mL or less.

Session cochair Dr. Gregg C. Fonarow said in an interview that he views PROTECT as a successful proof-of-concept study. But before biomarker-guided treatment of heart failure becomes part of guideline-recommended, routine outpatient care, it will be necessary to see if the Massachusetts General Hospital experience can be extended to other settings, including primary care practices, where many patients with heart failure receive their treatment. This will require a large multicenter trial with a diverse group of clinicians; randomization by site; and hard clinical end points, including mortality.

A proposal for such a study has been presented to the National Heart, Lung, and Blood Institute for funding consideration.

“It's a large and expensive trial, but the impact is potentially profound,” said Dr. Fonarow, professor of medicine and director of the Ahmanson-UCLA Cardiomyopathy Center, Los Angeles. “Given the costs of heart failure and the tremendous number of outpatient visits for this disease, if we truly had a well-validated guide using biomarkers, that would be a phenomenal advance.”

The PROTECT trial was sponsored in part by Roche Diagnostics. Dr. Januzzi declared he serves as a consultant to and speaker for the company.

The NT-proBNP–guided arm had a lower likelihood of worsening heart failure or heart failure hospitalization.

Source DR. JANUZZI

CHICAGO – A high-normal hematocrit was associated with an increased risk of new-onset heart failure in a Framingham Heart Study analysis.

“To our knowledge, this is the only study to show such a relationship in men and women in middle age. … Our results should prompt consideration of a cautious and measured approach to the aggressive treatment of low hematocrit in a variety of disease states,” Dr. Erin E. Coglianese said at the meeting.

The mechanism by which a hematocrit (HCT) within normal range is linked to heart failure is unclear. However, animal studies suggest one possibility – that a high-normal HCT could impair vasodilation as a result of scavenging of nitric oxide by hemoglobin, according to Dr. Coglianese of Massachusetts General Hospital, Boston.

To explore the relationship between HCT and the risk of heart failure, she and her coinvestigators turned to the Framingham Heart Study. They documented a strong, graded relationship between HCT level and the risk of developing heart failure in 3,523 Framingham participants aged 50-65 who were free of a history of heart failure at baseline and were followed prospectively for up to 20 years.

Indeed, individuals with a high-normal baseline HCT had almost double the risk of new-onset heart failure during follow-up, compared with those with a low HCT, even after adjustment for conventional risk factors for heart failure.

A low HCT was defined as 39% to less than 44% in men and 36% to less than 40% in women. Men with an HCT of 44% to less than 46% and women with a level of 40% to less than 42% were deemed as having a low-normal level. A normal HCT was defined as 46% to less than 50% in men and 42% to less than 46% in women. And a high-normal HCT was one greater than 50% in men or 46% in women.

When these definitions were used, the incidence of new-onset heart failure was 25/10,000 person-years in individuals with a low HCT level, 31/10,000 with a low-normal HCT, 38/10,000 with a normal HCT, and 48/10,000 in Framingham participants with high-normal HCT.

In a multivariate logistic regression analysis, the risk of new-onset heart failure, compared with the risk in those with a low HCT, was 27% greater in those with a low-normal HCT, 47% greater in those with a normal HCT, and 78% greater in those with a high-normal level. The analysis was adjusted for age, sex, total cholesterol, hypertension, body mass index, left ventricular hypertrophy, pack-years of smoking, and physical activity.

The big limitation of this study is that the original Framingham cohort, included in this analysis, looks quite different from contemporary patient populations. Specifically, roughly half of the men in the original cohort were smokers, Dr. Coglianese noted.

In contrast to these new findings regarding HCT and risk of new-onset heart failure, numerous studies have shown that in patients who already have heart failure, a low HCT is associated with an increased risk of heart failure hospitalization as well as all-cause mortality. It remains unclear, however, whether this increased risk of poor outcomes is due to pathophysiologic changes induced by low HCT, or if a low HCT is merely a marker of greater disease severity, she said.

Dr. Coglianese said she had no relevant financial disclosures.

CHICAGO – A high-normal hematocrit was associated with an increased risk of new-onset heart failure in a Framingham Heart Study analysis.

“To our knowledge, this is the only study to show such a relationship in men and women in middle age. … Our results should prompt consideration of a cautious and measured approach to the aggressive treatment of low hematocrit in a variety of disease states,” Dr. Erin E. Coglianese said at the meeting.

The mechanism by which a hematocrit (HCT) within normal range is linked to heart failure is unclear. However, animal studies suggest one possibility – that a high-normal HCT could impair vasodilation as a result of scavenging of nitric oxide by hemoglobin, according to Dr. Coglianese of Massachusetts General Hospital, Boston.

To explore the relationship between HCT and the risk of heart failure, she and her coinvestigators turned to the Framingham Heart Study. They documented a strong, graded relationship between HCT level and the risk of developing heart failure in 3,523 Framingham participants aged 50-65 who were free of a history of heart failure at baseline and were followed prospectively for up to 20 years.

Indeed, individuals with a high-normal baseline HCT had almost double the risk of new-onset heart failure during follow-up, compared with those with a low HCT, even after adjustment for conventional risk factors for heart failure.

A low HCT was defined as 39% to less than 44% in men and 36% to less than 40% in women. Men with an HCT of 44% to less than 46% and women with a level of 40% to less than 42% were deemed as having a low-normal level. A normal HCT was defined as 46% to less than 50% in men and 42% to less than 46% in women. And a high-normal HCT was one greater than 50% in men or 46% in women.

When these definitions were used, the incidence of new-onset heart failure was 25/10,000 person-years in individuals with a low HCT level, 31/10,000 with a low-normal HCT, 38/10,000 with a normal HCT, and 48/10,000 in Framingham participants with high-normal HCT.

In a multivariate logistic regression analysis, the risk of new-onset heart failure, compared with the risk in those with a low HCT, was 27% greater in those with a low-normal HCT, 47% greater in those with a normal HCT, and 78% greater in those with a high-normal level. The analysis was adjusted for age, sex, total cholesterol, hypertension, body mass index, left ventricular hypertrophy, pack-years of smoking, and physical activity.

The big limitation of this study is that the original Framingham cohort, included in this analysis, looks quite different from contemporary patient populations. Specifically, roughly half of the men in the original cohort were smokers, Dr. Coglianese noted.

In contrast to these new findings regarding HCT and risk of new-onset heart failure, numerous studies have shown that in patients who already have heart failure, a low HCT is associated with an increased risk of heart failure hospitalization as well as all-cause mortality. It remains unclear, however, whether this increased risk of poor outcomes is due to pathophysiologic changes induced by low HCT, or if a low HCT is merely a marker of greater disease severity, she said.

Dr. Coglianese said she had no relevant financial disclosures.

CHICAGO – A high-normal hematocrit was associated with an increased risk of new-onset heart failure in a Framingham Heart Study analysis.

“To our knowledge, this is the only study to show such a relationship in men and women in middle age. … Our results should prompt consideration of a cautious and measured approach to the aggressive treatment of low hematocrit in a variety of disease states,” Dr. Erin E. Coglianese said at the meeting.

The mechanism by which a hematocrit (HCT) within normal range is linked to heart failure is unclear. However, animal studies suggest one possibility – that a high-normal HCT could impair vasodilation as a result of scavenging of nitric oxide by hemoglobin, according to Dr. Coglianese of Massachusetts General Hospital, Boston.

To explore the relationship between HCT and the risk of heart failure, she and her coinvestigators turned to the Framingham Heart Study. They documented a strong, graded relationship between HCT level and the risk of developing heart failure in 3,523 Framingham participants aged 50-65 who were free of a history of heart failure at baseline and were followed prospectively for up to 20 years.

Indeed, individuals with a high-normal baseline HCT had almost double the risk of new-onset heart failure during follow-up, compared with those with a low HCT, even after adjustment for conventional risk factors for heart failure.

A low HCT was defined as 39% to less than 44% in men and 36% to less than 40% in women. Men with an HCT of 44% to less than 46% and women with a level of 40% to less than 42% were deemed as having a low-normal level. A normal HCT was defined as 46% to less than 50% in men and 42% to less than 46% in women. And a high-normal HCT was one greater than 50% in men or 46% in women.

When these definitions were used, the incidence of new-onset heart failure was 25/10,000 person-years in individuals with a low HCT level, 31/10,000 with a low-normal HCT, 38/10,000 with a normal HCT, and 48/10,000 in Framingham participants with high-normal HCT.

In a multivariate logistic regression analysis, the risk of new-onset heart failure, compared with the risk in those with a low HCT, was 27% greater in those with a low-normal HCT, 47% greater in those with a normal HCT, and 78% greater in those with a high-normal level. The analysis was adjusted for age, sex, total cholesterol, hypertension, body mass index, left ventricular hypertrophy, pack-years of smoking, and physical activity.

The big limitation of this study is that the original Framingham cohort, included in this analysis, looks quite different from contemporary patient populations. Specifically, roughly half of the men in the original cohort were smokers, Dr. Coglianese noted.

In contrast to these new findings regarding HCT and risk of new-onset heart failure, numerous studies have shown that in patients who already have heart failure, a low HCT is associated with an increased risk of heart failure hospitalization as well as all-cause mortality. It remains unclear, however, whether this increased risk of poor outcomes is due to pathophysiologic changes induced by low HCT, or if a low HCT is merely a marker of greater disease severity, she said.

Dr. Coglianese said she had no relevant financial disclosures.

CHICAGO – Keeping the bedroom warm at night during the cold winter months curbs the morning surge in blood pressure, according to a randomized Japanese trial.

This finding may help explain the well-established increased mortality due to heart disease and stroke during the winter months.

The data from this study indicate that if the ambient bedroom temperature is lower, morning blood pressure will be higher, the morning blood pressure surge will be greater, and there will be increased blood pressure variability during the 24-hour day, increasing the risk of a cardiac or cerebrovascular event, Dr. Keigo Saeki asserted at the meeting.

The investigators randomized 140 healthy 18- to 65-year-old participants to spend a night in either an inadequately heated room at 12° C (54° F) or a room maintained at 22° C (72° F). Participants were required to remain in the room between 9 p.m. and 6 a.m., stay awake until 11 p.m., and rise by 6 a.m. Blood pressure was measured every 30 minutes through the night. The subjects had access to all the clothing and blankets they needed to stay comfortable, said Dr. Saeki of Nara (Japan) Medical University.

Mean systolic blood pressure during the first 2 hours after awakening in the morning was 121.1 mm Hg in subjects who slept in the cold room, significantly higher than the 114.0 mm Hg for those in the warm room. The morning systolic blood pressure surge also was significantly higher in subjects after a night in the inadequately heated room: 21.9 mm Hg, compared with 14.3 mm Hg after a night in the warm room. However, there was no difference between the two study groups in terms of lowest sleeping systolic blood pressure, which averaged 99 mm Hg across three readings.

Dr. Saeki declared having no relevant disclosures.

CHICAGO – Keeping the bedroom warm at night during the cold winter months curbs the morning surge in blood pressure, according to a randomized Japanese trial.

This finding may help explain the well-established increased mortality due to heart disease and stroke during the winter months.

The data from this study indicate that if the ambient bedroom temperature is lower, morning blood pressure will be higher, the morning blood pressure surge will be greater, and there will be increased blood pressure variability during the 24-hour day, increasing the risk of a cardiac or cerebrovascular event, Dr. Keigo Saeki asserted at the meeting.

The investigators randomized 140 healthy 18- to 65-year-old participants to spend a night in either an inadequately heated room at 12° C (54° F) or a room maintained at 22° C (72° F). Participants were required to remain in the room between 9 p.m. and 6 a.m., stay awake until 11 p.m., and rise by 6 a.m. Blood pressure was measured every 30 minutes through the night. The subjects had access to all the clothing and blankets they needed to stay comfortable, said Dr. Saeki of Nara (Japan) Medical University.

Mean systolic blood pressure during the first 2 hours after awakening in the morning was 121.1 mm Hg in subjects who slept in the cold room, significantly higher than the 114.0 mm Hg for those in the warm room. The morning systolic blood pressure surge also was significantly higher in subjects after a night in the inadequately heated room: 21.9 mm Hg, compared with 14.3 mm Hg after a night in the warm room. However, there was no difference between the two study groups in terms of lowest sleeping systolic blood pressure, which averaged 99 mm Hg across three readings.

Dr. Saeki declared having no relevant disclosures.

CHICAGO – Keeping the bedroom warm at night during the cold winter months curbs the morning surge in blood pressure, according to a randomized Japanese trial.

This finding may help explain the well-established increased mortality due to heart disease and stroke during the winter months.

The data from this study indicate that if the ambient bedroom temperature is lower, morning blood pressure will be higher, the morning blood pressure surge will be greater, and there will be increased blood pressure variability during the 24-hour day, increasing the risk of a cardiac or cerebrovascular event, Dr. Keigo Saeki asserted at the meeting.

The investigators randomized 140 healthy 18- to 65-year-old participants to spend a night in either an inadequately heated room at 12° C (54° F) or a room maintained at 22° C (72° F). Participants were required to remain in the room between 9 p.m. and 6 a.m., stay awake until 11 p.m., and rise by 6 a.m. Blood pressure was measured every 30 minutes through the night. The subjects had access to all the clothing and blankets they needed to stay comfortable, said Dr. Saeki of Nara (Japan) Medical University.

Mean systolic blood pressure during the first 2 hours after awakening in the morning was 121.1 mm Hg in subjects who slept in the cold room, significantly higher than the 114.0 mm Hg for those in the warm room. The morning systolic blood pressure surge also was significantly higher in subjects after a night in the inadequately heated room: 21.9 mm Hg, compared with 14.3 mm Hg after a night in the warm room. However, there was no difference between the two study groups in terms of lowest sleeping systolic blood pressure, which averaged 99 mm Hg across three readings.

Dr. Saeki declared having no relevant disclosures.

DENVER –Raising cigarette taxes has the unwanted effect of increasing alcohol consumption, including binge and heavy drinking.

This relationship is an example of what economists call a cross-price or substitution effect. And it’s something policy makers need to be cognizant of, Deborah L. McLellan said at the meeting.

She analyzed 6 years of cross-sectional data from the Centers for Disease Control and Prevention’s annual Behavioral Risk Factor Surveillance System surveys carried out in 2001-2006. Interviews were conducted with 1,323,758 adults living in nearly every state in the country.

Her multivariate logistic regression analysis concluded that for every 1 dollar increase in the price of a pack of cigarettes, the ranks of current smokers drop by a highly significant 5%. That’s consistent with the classic economic theory of consumer demand, which holds that raising the price of a commodity decreases consumption.

But the analysis also showed that a 1 dollar per pack price increase was associated with a 29% increase in the odds of having consumed alcohol during the last month, a 12% increase in binge drinking, and a 10% increase in heavy drinking, defined in the study as more than one drink per day in women and more than two in men.

"I want to be clear that the message here is not ‘Let’s stop increasing cigarette taxes.’ That’s not my message at all. But this study is contributing to other literature out there that’s finding there are substitution effects, so advocates and policy makers and indeed researchers need to prepare for some of these unintended consequences of tobacco taxation policy," said Ms. McLellan of the Heller School for Social Policy and Management at Brandeis University, Waltham, Mass.

"There needs to be more collaboration between tobacco control advocates and those who work in alcohol prevention. We all know we tend to work in our silos, but people certainly do drink and smoke, and we need to catch up with them," she added.

The researcher noted that alcohol and tobacco use carry "staggering" human and economic costs. It’s estimated that 438,000 deaths occur annually from tobacco in the United States, and 98,000 because of alcohol. Twenty percent of Americans were smokers in 2006 and 51% were drinkers, including 23% who were binge drinkers and 7% who were heavy drinkers. Twenty-two percent of Americans were co-users.

She declared having no financial conflicts regarding the study, which she is conducting for her dissertation.

DENVER –Raising cigarette taxes has the unwanted effect of increasing alcohol consumption, including binge and heavy drinking.

This relationship is an example of what economists call a cross-price or substitution effect. And it’s something policy makers need to be cognizant of, Deborah L. McLellan said at the meeting.

She analyzed 6 years of cross-sectional data from the Centers for Disease Control and Prevention’s annual Behavioral Risk Factor Surveillance System surveys carried out in 2001-2006. Interviews were conducted with 1,323,758 adults living in nearly every state in the country.

Her multivariate logistic regression analysis concluded that for every 1 dollar increase in the price of a pack of cigarettes, the ranks of current smokers drop by a highly significant 5%. That’s consistent with the classic economic theory of consumer demand, which holds that raising the price of a commodity decreases consumption.

But the analysis also showed that a 1 dollar per pack price increase was associated with a 29% increase in the odds of having consumed alcohol during the last month, a 12% increase in binge drinking, and a 10% increase in heavy drinking, defined in the study as more than one drink per day in women and more than two in men.

"I want to be clear that the message here is not ‘Let’s stop increasing cigarette taxes.’ That’s not my message at all. But this study is contributing to other literature out there that’s finding there are substitution effects, so advocates and policy makers and indeed researchers need to prepare for some of these unintended consequences of tobacco taxation policy," said Ms. McLellan of the Heller School for Social Policy and Management at Brandeis University, Waltham, Mass.

"There needs to be more collaboration between tobacco control advocates and those who work in alcohol prevention. We all know we tend to work in our silos, but people certainly do drink and smoke, and we need to catch up with them," she added.

The researcher noted that alcohol and tobacco use carry "staggering" human and economic costs. It’s estimated that 438,000 deaths occur annually from tobacco in the United States, and 98,000 because of alcohol. Twenty percent of Americans were smokers in 2006 and 51% were drinkers, including 23% who were binge drinkers and 7% who were heavy drinkers. Twenty-two percent of Americans were co-users.

She declared having no financial conflicts regarding the study, which she is conducting for her dissertation.

DENVER –Raising cigarette taxes has the unwanted effect of increasing alcohol consumption, including binge and heavy drinking.

This relationship is an example of what economists call a cross-price or substitution effect. And it’s something policy makers need to be cognizant of, Deborah L. McLellan said at the meeting.

She analyzed 6 years of cross-sectional data from the Centers for Disease Control and Prevention’s annual Behavioral Risk Factor Surveillance System surveys carried out in 2001-2006. Interviews were conducted with 1,323,758 adults living in nearly every state in the country.

Her multivariate logistic regression analysis concluded that for every 1 dollar increase in the price of a pack of cigarettes, the ranks of current smokers drop by a highly significant 5%. That’s consistent with the classic economic theory of consumer demand, which holds that raising the price of a commodity decreases consumption.

But the analysis also showed that a 1 dollar per pack price increase was associated with a 29% increase in the odds of having consumed alcohol during the last month, a 12% increase in binge drinking, and a 10% increase in heavy drinking, defined in the study as more than one drink per day in women and more than two in men.

"I want to be clear that the message here is not ‘Let’s stop increasing cigarette taxes.’ That’s not my message at all. But this study is contributing to other literature out there that’s finding there are substitution effects, so advocates and policy makers and indeed researchers need to prepare for some of these unintended consequences of tobacco taxation policy," said Ms. McLellan of the Heller School for Social Policy and Management at Brandeis University, Waltham, Mass.

"There needs to be more collaboration between tobacco control advocates and those who work in alcohol prevention. We all know we tend to work in our silos, but people certainly do drink and smoke, and we need to catch up with them," she added.

The researcher noted that alcohol and tobacco use carry "staggering" human and economic costs. It’s estimated that 438,000 deaths occur annually from tobacco in the United States, and 98,000 because of alcohol. Twenty percent of Americans were smokers in 2006 and 51% were drinkers, including 23% who were binge drinkers and 7% who were heavy drinkers. Twenty-two percent of Americans were co-users.

She declared having no financial conflicts regarding the study, which she is conducting for her dissertation.

SNOWMASS, Colo. – The past 12 months have brought a slew of studies making a persuasive case for hydroxychloroquine as a far more important drug in lupus than previously thought. Indeed, the drug could now even be considered essential.

"In 2011, all lupus patients should receive hydroxychloroquine," Dr. David Wofsy flatly declared at a symposium sponsored by the American College of Rheumatology.

"The indication for hydroxychloroquine in lupus is lupus," added Dr. Wofsy, professor of medicine and microbiology/immunology at the University of California, San Francisco.

There is now solid evidence that hydroxychloroquine (Plaquenil) prevents lupus flares, treats the skin manifestations of the disease, protects against thromboembolic events, prevents cardiac neonatal lupus, and prolongs life.

"It will be a very long time before we've proven that any biologic therapy can do all those things," Dr. Wofsy, who is also chief of rheumatology at the San Francisco Veterans Affairs Medical Center.

He cited several eye-opening hydroxychloroquine studies that were presented at the 2010 annual meeting of the ACR. In one, investigators from the Systemic Lupus International Collaborating Clinics (SLICC) presented findings from an international registry of 1,593 lupus patients followed since 2000. In a multivariate analysis, antimalarial therapy was independently associated with a highly significant 70% reduction in mortality.

It's particularly noteworthy that in this report from 35 of the world's leading lupus centers, only 65% of patients were on antimalarial therapy. In light of the impressive results of the SLICC study and the other very recent evidence, that's an embarrassingly low rate. In fact, Dr. Wofsy urged audience members to pull the records of all their lupus patients and put those who aren't now taking hydroxychloroquine on the drug forthwith.

Also at the 2010 ACR meeting, French investigators presented a prospective study of 300 SLE patients on hydroxychloroquine for cutaneous lupus. The researchers found that serum drug levels were strongly correlated with clinical response. The 114 patients with a complete response had a mean hydroxychloroquine level of 910 ng/mL. The 100 nonresponders had a mean level of 569 ng/mL, while partial responders averaged 692 ng/mL.

The thromboprotective effect of hydroxychloroquine was demonstrated in a University of Toronto case-control study involving newly diagnosed lupus patients prospectively followed long-term. Fifty-four patients who experienced thromboembolic events were matched with 108 lupus patients who did not. In a multivariate analysis adjusted for disease severity and duration and calendar year, antimalarial therapy was associated with a 68% reduction in the risk of thromboembolic events. The protective effect was similar for arterial as well as venous thrombosis (Arthritis Rheum. 2010;62:863-8).

Another recently published study highlighted hydroxychloroquine's protective effect against cardiac neonatal lupus in children exposed to the drug in utero. The retrospective study involved 50 children with cardiac neonatal lupus and 151 controls without this condition. Fourteen percent of the children with cardiac neonatal lupus were exposed to antimalarial therapy in utero, compared with 37% of controls. This translated to an adjusted 72% reduction in the likelihood of neonatal lupus heart block in kids with fetal exposure to the drug (Ann. Rheum. Dis. 2010;69:1827-30).

Dr. Wofsy noted the irony that this new appreciation of hydroxychloroquine's abundant benefits in lupus comes on the eve of what is widely anticipated to be regulatory approval of the first drug ever to be approved for lupus: belimumab (Benlysta), the fully human monoclonal antibody directed against the B-lymphocyte stimulator. Last November, a Food and Drug Administration advisory panel recommended marketing approval for belimumab by a 13-2 margin. The FDA has announced it will issue its decision in mid-March.

Is belimumab a better drug for lupus than hydroxychloroquine? Many physicians might reflexively assume that a very costly new biologic agent for lupus must be better than an old, cheap antimalarial, but that's far from certain at this point, he said.

"All of us know that Plaquenil is not the solution to lupus. It is far from the solution to lupus. But it is a reasonable low bar to place when we think of the biologic therapies," he said in urging his colleagues not to underestimate the value of the antimalarial or fall prey to the coming massive marketing hype for belimumab.

Also at the Snowmass conference, Dr. Chester V. Oddis forecast that an inevitable consequence of putting lots more lupus patients on hydroxychloroquine will be an increase in drug-induced myopathies. The antimalarial is one of the drugs that can cause these myopathies, which mimic inflammatory myopathies in terms of symptoms, but without the attendant inflammation. The classic histopathology of hydroxychloroquine myopathy includes necrotic and vacuolated muscle fibers on H&E staining, pathognomic curvilinear inclusions on electron microscopy.

Other drugs that can cause these noninflammatory myopathies include statins and colchicine as well as alcohol, noted Dr. Oddis, professor of medicine at the University of Pittsburgh.

Dr. Wofsy declared that he serves as a consultant to Bristol-Myers Squibb and has received research grants from numerous other companies developing new treatments for autoimmune diseases. Dr. Odis reported he had no relevant financial disclosures.

SNOWMASS, Colo. – The past 12 months have brought a slew of studies making a persuasive case for hydroxychloroquine as a far more important drug in lupus than previously thought. Indeed, the drug could now even be considered essential.

"In 2011, all lupus patients should receive hydroxychloroquine," Dr. David Wofsy flatly declared at a symposium sponsored by the American College of Rheumatology.

"The indication for hydroxychloroquine in lupus is lupus," added Dr. Wofsy, professor of medicine and microbiology/immunology at the University of California, San Francisco.

There is now solid evidence that hydroxychloroquine (Plaquenil) prevents lupus flares, treats the skin manifestations of the disease, protects against thromboembolic events, prevents cardiac neonatal lupus, and prolongs life.

"It will be a very long time before we've proven that any biologic therapy can do all those things," Dr. Wofsy, who is also chief of rheumatology at the San Francisco Veterans Affairs Medical Center.

He cited several eye-opening hydroxychloroquine studies that were presented at the 2010 annual meeting of the ACR. In one, investigators from the Systemic Lupus International Collaborating Clinics (SLICC) presented findings from an international registry of 1,593 lupus patients followed since 2000. In a multivariate analysis, antimalarial therapy was independently associated with a highly significant 70% reduction in mortality.

It's particularly noteworthy that in this report from 35 of the world's leading lupus centers, only 65% of patients were on antimalarial therapy. In light of the impressive results of the SLICC study and the other very recent evidence, that's an embarrassingly low rate. In fact, Dr. Wofsy urged audience members to pull the records of all their lupus patients and put those who aren't now taking hydroxychloroquine on the drug forthwith.

Also at the 2010 ACR meeting, French investigators presented a prospective study of 300 SLE patients on hydroxychloroquine for cutaneous lupus. The researchers found that serum drug levels were strongly correlated with clinical response. The 114 patients with a complete response had a mean hydroxychloroquine level of 910 ng/mL. The 100 nonresponders had a mean level of 569 ng/mL, while partial responders averaged 692 ng/mL.

The thromboprotective effect of hydroxychloroquine was demonstrated in a University of Toronto case-control study involving newly diagnosed lupus patients prospectively followed long-term. Fifty-four patients who experienced thromboembolic events were matched with 108 lupus patients who did not. In a multivariate analysis adjusted for disease severity and duration and calendar year, antimalarial therapy was associated with a 68% reduction in the risk of thromboembolic events. The protective effect was similar for arterial as well as venous thrombosis (Arthritis Rheum. 2010;62:863-8).

Another recently published study highlighted hydroxychloroquine's protective effect against cardiac neonatal lupus in children exposed to the drug in utero. The retrospective study involved 50 children with cardiac neonatal lupus and 151 controls without this condition. Fourteen percent of the children with cardiac neonatal lupus were exposed to antimalarial therapy in utero, compared with 37% of controls. This translated to an adjusted 72% reduction in the likelihood of neonatal lupus heart block in kids with fetal exposure to the drug (Ann. Rheum. Dis. 2010;69:1827-30).

Dr. Wofsy noted the irony that this new appreciation of hydroxychloroquine's abundant benefits in lupus comes on the eve of what is widely anticipated to be regulatory approval of the first drug ever to be approved for lupus: belimumab (Benlysta), the fully human monoclonal antibody directed against the B-lymphocyte stimulator. Last November, a Food and Drug Administration advisory panel recommended marketing approval for belimumab by a 13-2 margin. The FDA has announced it will issue its decision in mid-March.

Is belimumab a better drug for lupus than hydroxychloroquine? Many physicians might reflexively assume that a very costly new biologic agent for lupus must be better than an old, cheap antimalarial, but that's far from certain at this point, he said.

"All of us know that Plaquenil is not the solution to lupus. It is far from the solution to lupus. But it is a reasonable low bar to place when we think of the biologic therapies," he said in urging his colleagues not to underestimate the value of the antimalarial or fall prey to the coming massive marketing hype for belimumab.

Also at the Snowmass conference, Dr. Chester V. Oddis forecast that an inevitable consequence of putting lots more lupus patients on hydroxychloroquine will be an increase in drug-induced myopathies. The antimalarial is one of the drugs that can cause these myopathies, which mimic inflammatory myopathies in terms of symptoms, but without the attendant inflammation. The classic histopathology of hydroxychloroquine myopathy includes necrotic and vacuolated muscle fibers on H&E staining, pathognomic curvilinear inclusions on electron microscopy.

Other drugs that can cause these noninflammatory myopathies include statins and colchicine as well as alcohol, noted Dr. Oddis, professor of medicine at the University of Pittsburgh.

Dr. Wofsy declared that he serves as a consultant to Bristol-Myers Squibb and has received research grants from numerous other companies developing new treatments for autoimmune diseases. Dr. Odis reported he had no relevant financial disclosures.

SNOWMASS, Colo. – The past 12 months have brought a slew of studies making a persuasive case for hydroxychloroquine as a far more important drug in lupus than previously thought. Indeed, the drug could now even be considered essential.

"In 2011, all lupus patients should receive hydroxychloroquine," Dr. David Wofsy flatly declared at a symposium sponsored by the American College of Rheumatology.

"The indication for hydroxychloroquine in lupus is lupus," added Dr. Wofsy, professor of medicine and microbiology/immunology at the University of California, San Francisco.

There is now solid evidence that hydroxychloroquine (Plaquenil) prevents lupus flares, treats the skin manifestations of the disease, protects against thromboembolic events, prevents cardiac neonatal lupus, and prolongs life.

"It will be a very long time before we've proven that any biologic therapy can do all those things," Dr. Wofsy, who is also chief of rheumatology at the San Francisco Veterans Affairs Medical Center.

He cited several eye-opening hydroxychloroquine studies that were presented at the 2010 annual meeting of the ACR. In one, investigators from the Systemic Lupus International Collaborating Clinics (SLICC) presented findings from an international registry of 1,593 lupus patients followed since 2000. In a multivariate analysis, antimalarial therapy was independently associated with a highly significant 70% reduction in mortality.

It's particularly noteworthy that in this report from 35 of the world's leading lupus centers, only 65% of patients were on antimalarial therapy. In light of the impressive results of the SLICC study and the other very recent evidence, that's an embarrassingly low rate. In fact, Dr. Wofsy urged audience members to pull the records of all their lupus patients and put those who aren't now taking hydroxychloroquine on the drug forthwith.

Also at the 2010 ACR meeting, French investigators presented a prospective study of 300 SLE patients on hydroxychloroquine for cutaneous lupus. The researchers found that serum drug levels were strongly correlated with clinical response. The 114 patients with a complete response had a mean hydroxychloroquine level of 910 ng/mL. The 100 nonresponders had a mean level of 569 ng/mL, while partial responders averaged 692 ng/mL.

The thromboprotective effect of hydroxychloroquine was demonstrated in a University of Toronto case-control study involving newly diagnosed lupus patients prospectively followed long-term. Fifty-four patients who experienced thromboembolic events were matched with 108 lupus patients who did not. In a multivariate analysis adjusted for disease severity and duration and calendar year, antimalarial therapy was associated with a 68% reduction in the risk of thromboembolic events. The protective effect was similar for arterial as well as venous thrombosis (Arthritis Rheum. 2010;62:863-8).

Another recently published study highlighted hydroxychloroquine's protective effect against cardiac neonatal lupus in children exposed to the drug in utero. The retrospective study involved 50 children with cardiac neonatal lupus and 151 controls without this condition. Fourteen percent of the children with cardiac neonatal lupus were exposed to antimalarial therapy in utero, compared with 37% of controls. This translated to an adjusted 72% reduction in the likelihood of neonatal lupus heart block in kids with fetal exposure to the drug (Ann. Rheum. Dis. 2010;69:1827-30).

Dr. Wofsy noted the irony that this new appreciation of hydroxychloroquine's abundant benefits in lupus comes on the eve of what is widely anticipated to be regulatory approval of the first drug ever to be approved for lupus: belimumab (Benlysta), the fully human monoclonal antibody directed against the B-lymphocyte stimulator. Last November, a Food and Drug Administration advisory panel recommended marketing approval for belimumab by a 13-2 margin. The FDA has announced it will issue its decision in mid-March.

Is belimumab a better drug for lupus than hydroxychloroquine? Many physicians might reflexively assume that a very costly new biologic agent for lupus must be better than an old, cheap antimalarial, but that's far from certain at this point, he said.

"All of us know that Plaquenil is not the solution to lupus. It is far from the solution to lupus. But it is a reasonable low bar to place when we think of the biologic therapies," he said in urging his colleagues not to underestimate the value of the antimalarial or fall prey to the coming massive marketing hype for belimumab.

Also at the Snowmass conference, Dr. Chester V. Oddis forecast that an inevitable consequence of putting lots more lupus patients on hydroxychloroquine will be an increase in drug-induced myopathies. The antimalarial is one of the drugs that can cause these myopathies, which mimic inflammatory myopathies in terms of symptoms, but without the attendant inflammation. The classic histopathology of hydroxychloroquine myopathy includes necrotic and vacuolated muscle fibers on H&E staining, pathognomic curvilinear inclusions on electron microscopy.

Other drugs that can cause these noninflammatory myopathies include statins and colchicine as well as alcohol, noted Dr. Oddis, professor of medicine at the University of Pittsburgh.

Dr. Wofsy declared that he serves as a consultant to Bristol-Myers Squibb and has received research grants from numerous other companies developing new treatments for autoimmune diseases. Dr. Odis reported he had no relevant financial disclosures.

SNOWMASS, Colo. - Until further testing confirms or disproves the promise of an oral formulation of treprostinil that is making its way through the developmental pipeline for management of Raynaud's phenomenon and the ischemic finger, physicians will have to continue to make do with modestly efficacious agents that all are best employed in conjunction with background therapy using a long-acting calcium channel blocker titrated to the maximum tolerated dose.

Calling the developmental oral treprostinil agent particularly exciting, Dr. Frederick M. Wigley noted that the prostacyclin analogs are highly effective in cases of Raynaud's with severe digital ischemia, but the ones available now have to be given intravenously, which is costly and inconvenient.

An effective oral prostacyclin would be a major development. The early clinical trials of oral treprostinil have been quite promising, and the drug is now moving into advanced trials for Raynaud's phenomenon as well as for pulmonary arterial hypertension, according to Dr. Wigley, professor of medicine and director of the scleroderma center at Johns Hopkins University, Baltimore.

However, for now, "the kingpin of our therapy is usually the calcium channel blocker," he observed at a symposium sponsored by the American College of Rheumatology.

He highlighted the agents variously prescribed for Raynaud's and how they fit into his management strategy – and in some cases, why they do not.

His first-line drug for Raynaud's and the ischemic finger is amlodipine, at a starting dose of 5 mg that is titrated to 20 mg/day. This typically results in a 35%-40% reduction in patient-rated symptom severity scores, which he characterized as "a modest benefit." In addition, full-dose calcium channel blocker therapy also appears to reduce the incidence of digital ulcers, in Dr. Wigley's experience.

Other medications often used for Raynaud's phenomenon include:

• Topical nitrates: This popular therapy improves blood flow in affected fingers, but at the price of headaches and other side effects that many patients find intolerable.

"In my practice, I generally use topical nitrates when I have a patient with one finger that's in trouble and I'm trying to get a bit of blush to the surface of the skin. It's a therapy that's generally not tolerated when used on a daily basis on all the fingers," the rheumatologist said.

• Other topicals: EMLA cream (2.5% lidocaine/2.5% prilocaine in a eutectic mixture) provides numbing as well as vasodilation. "I use it often in patients who have painful fingertips. It's probably not quite as potent as the topical nitrates," Dr. Wigley said.

Several studies have shown that topical minoxidil is ineffective. Topical niacin is helpful in bringing a blush to ischemic skin, but it doesn't address deeper ischemic events.

• ACE inhibitors and angiotensin receptor blockers: ACE inhibitors are famously effective in preventing fatal renal crisis in scleroderma patients, but they don't reduce the frequency or severity of Raynaud's episodes, as was demonstrated in a large, randomized, double-blind clinical trial (Arthritis Rheum. 2007;56:3837-46).

In contrast, the angiotensin receptor blocker losartan at 50 mg/day has been shown in a randomized trial to be an effective alternative to calcium channel blocker therapy (Arthritis Rheum. 1999;42:2646-55). However, Dr. Wigley said his own clinical experience has been that losartan's benefits are milder than with a long-acting calcium channel blocker pushed to the maximum tolerated dose.

• Selective serotonin reuptake inhibitors: Activated platelets in Raynaud’s release serotonin, a vasoconstrictor. In a 53-patient randomized, crossover trial, fluoxetine (Prozac) at 20 mg/day resulted in greater reductions in the frequency, duration, and severity of Raynaud's attacks compared to baseline than did nifedipine at 40 mg/day (Rheumatology 2001;40:1038-43).

• Alpha adrenergic blockers: Prazosin was once a very popular treatment, but it has given way to the long-acting calcium channel blockers, which are more effective. Prazosin is primarily an alpha-1 inhibitor, and there aren't a lot of alpha-1 receptors on vascular smooth muscle cells. The alpha-2C receptor is the key player at that site. Selective alpha-2C receptor inhibitors are in development.

• Phosphodiesterase inhibitors: "I must say that I'm generally disappointed with these drugs, and when I use them I do so in conjunction with a calcium channel blocker for their best benefit," Dr. Wigley said.

• Prostaglandins: A Cochrane review of seven clinical trials in patients with Raynaud's phenomenon and scleroderma concluded that prostacyclin analogs reduced attack frequency and severity, improved digital lesions, and resulted in favorable physician assessments of treatment outcome (Cochrane Database of Syst. Rev. 1998;2:CD000953).

European physicians have pioneered cyclic therapy with intravenous iloprost in patients with severe Raynaud's, giving it daily, weekly, or monthly during the winter months and less frequently as needed during warmer weather. Dr. Wigley said that he utilizes intravenous epoprostenol as a key part of his approach to patients with an acute digital ischemic crisis.

• Botulinum toxin type A: Vascular surgeons report glowing results, with rapid improvement after injection of Botox at the base of the finger. But there have been no controlled trials and Dr. Wigley said that he remains skeptical, having used it in a critical situation, with a disappointing lack of acute vasodilation.

"I don't know if it really works or not. We'll have to wait for a good study," he said.

• Bosentan: In the Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess the Effect of Bosentan on Healing and Prevention of Ischemic Digital Ulcers in Patients With Systemic Sclerosis (RAPIDS-1) trial, patients treated with the endothelin inhibitor had a 48% decrease in new ulcers compared to placebo during a 16-week period. They also experienced significantly improved hand function, although there was no benefit in terms of healing of existing ulcers or patient-assessed Raynaud's severity (Arthritis Rheum. 2004;50:3985-93). These findings suggest bosentan may have a role in a protective strategy aimed at reducing ischemic events, according to Dr. Wigley.

• Antioxidants: Most studies have been negative.

At the Johns Hopkins scleroderma center, the management approach taken in a new patient with Raynaud’s phenomenon with digital ischemia is to first stop the aggravating environmental factors: cold, trauma, smoking, and stress.

"None of the drugs we have is more potent than warm temperatures," the rheumatologist stressed.

Dr. Wigley puts the patient on amlodipine along with aspirin at 81 mg/day, aimed at preventing vascular occlusion. If the patient remains severely ischemic despite maximum-dose amlodipine or has digital ulcers he adds a second vasodilator, typically a phosphodiesterase inhibitor such as sildenafil, which has been shown to reduce the frequency and duration of Raynaud's attacks compared to placebo in a small, double-blind, crossover, randomized trial (Circulation 2005;112:2980-5).

He said he has a low threshold for putting Raynaud's patients on statin therapy as a vascular protection strategy. Dr. Wigley said that he was favorably impressed by findings from a randomized trial in which scleroderma patients placed on atorvastatin at 40 mg/day had a significant decrease in new ulcers compared to placebo, as well as better scores on pain scales and improved endothelial markers (J. Rheumatol. 2008;35:1801-9).

Dr. Wigley declared that he receives consulting fees and/or research grants from Actelion, Amira, Kinemed, Medimmune, Novartis, Orion, Pfizer, and United Therapeutics.

SNOWMASS, Colo. - Until further testing confirms or disproves the promise of an oral formulation of treprostinil that is making its way through the developmental pipeline for management of Raynaud's phenomenon and the ischemic finger, physicians will have to continue to make do with modestly efficacious agents that all are best employed in conjunction with background therapy using a long-acting calcium channel blocker titrated to the maximum tolerated dose.

Calling the developmental oral treprostinil agent particularly exciting, Dr. Frederick M. Wigley noted that the prostacyclin analogs are highly effective in cases of Raynaud's with severe digital ischemia, but the ones available now have to be given intravenously, which is costly and inconvenient.

An effective oral prostacyclin would be a major development. The early clinical trials of oral treprostinil have been quite promising, and the drug is now moving into advanced trials for Raynaud's phenomenon as well as for pulmonary arterial hypertension, according to Dr. Wigley, professor of medicine and director of the scleroderma center at Johns Hopkins University, Baltimore.

However, for now, "the kingpin of our therapy is usually the calcium channel blocker," he observed at a symposium sponsored by the American College of Rheumatology.

He highlighted the agents variously prescribed for Raynaud's and how they fit into his management strategy – and in some cases, why they do not.

His first-line drug for Raynaud's and the ischemic finger is amlodipine, at a starting dose of 5 mg that is titrated to 20 mg/day. This typically results in a 35%-40% reduction in patient-rated symptom severity scores, which he characterized as "a modest benefit." In addition, full-dose calcium channel blocker therapy also appears to reduce the incidence of digital ulcers, in Dr. Wigley's experience.

Other medications often used for Raynaud's phenomenon include:

• Topical nitrates: This popular therapy improves blood flow in affected fingers, but at the price of headaches and other side effects that many patients find intolerable.

"In my practice, I generally use topical nitrates when I have a patient with one finger that's in trouble and I'm trying to get a bit of blush to the surface of the skin. It's a therapy that's generally not tolerated when used on a daily basis on all the fingers," the rheumatologist said.

• Other topicals: EMLA cream (2.5% lidocaine/2.5% prilocaine in a eutectic mixture) provides numbing as well as vasodilation. "I use it often in patients who have painful fingertips. It's probably not quite as potent as the topical nitrates," Dr. Wigley said.

Several studies have shown that topical minoxidil is ineffective. Topical niacin is helpful in bringing a blush to ischemic skin, but it doesn't address deeper ischemic events.

• ACE inhibitors and angiotensin receptor blockers: ACE inhibitors are famously effective in preventing fatal renal crisis in scleroderma patients, but they don't reduce the frequency or severity of Raynaud's episodes, as was demonstrated in a large, randomized, double-blind clinical trial (Arthritis Rheum. 2007;56:3837-46).

In contrast, the angiotensin receptor blocker losartan at 50 mg/day has been shown in a randomized trial to be an effective alternative to calcium channel blocker therapy (Arthritis Rheum. 1999;42:2646-55). However, Dr. Wigley said his own clinical experience has been that losartan's benefits are milder than with a long-acting calcium channel blocker pushed to the maximum tolerated dose.

• Selective serotonin reuptake inhibitors: Activated platelets in Raynaud’s release serotonin, a vasoconstrictor. In a 53-patient randomized, crossover trial, fluoxetine (Prozac) at 20 mg/day resulted in greater reductions in the frequency, duration, and severity of Raynaud's attacks compared to baseline than did nifedipine at 40 mg/day (Rheumatology 2001;40:1038-43).

• Alpha adrenergic blockers: Prazosin was once a very popular treatment, but it has given way to the long-acting calcium channel blockers, which are more effective. Prazosin is primarily an alpha-1 inhibitor, and there aren't a lot of alpha-1 receptors on vascular smooth muscle cells. The alpha-2C receptor is the key player at that site. Selective alpha-2C receptor inhibitors are in development.

• Phosphodiesterase inhibitors: "I must say that I'm generally disappointed with these drugs, and when I use them I do so in conjunction with a calcium channel blocker for their best benefit," Dr. Wigley said.

• Prostaglandins: A Cochrane review of seven clinical trials in patients with Raynaud's phenomenon and scleroderma concluded that prostacyclin analogs reduced attack frequency and severity, improved digital lesions, and resulted in favorable physician assessments of treatment outcome (Cochrane Database of Syst. Rev. 1998;2:CD000953).

European physicians have pioneered cyclic therapy with intravenous iloprost in patients with severe Raynaud's, giving it daily, weekly, or monthly during the winter months and less frequently as needed during warmer weather. Dr. Wigley said that he utilizes intravenous epoprostenol as a key part of his approach to patients with an acute digital ischemic crisis.

• Botulinum toxin type A: Vascular surgeons report glowing results, with rapid improvement after injection of Botox at the base of the finger. But there have been no controlled trials and Dr. Wigley said that he remains skeptical, having used it in a critical situation, with a disappointing lack of acute vasodilation.

"I don't know if it really works or not. We'll have to wait for a good study," he said.

• Bosentan: In the Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess the Effect of Bosentan on Healing and Prevention of Ischemic Digital Ulcers in Patients With Systemic Sclerosis (RAPIDS-1) trial, patients treated with the endothelin inhibitor had a 48% decrease in new ulcers compared to placebo during a 16-week period. They also experienced significantly improved hand function, although there was no benefit in terms of healing of existing ulcers or patient-assessed Raynaud's severity (Arthritis Rheum. 2004;50:3985-93). These findings suggest bosentan may have a role in a protective strategy aimed at reducing ischemic events, according to Dr. Wigley.

• Antioxidants: Most studies have been negative.

At the Johns Hopkins scleroderma center, the management approach taken in a new patient with Raynaud’s phenomenon with digital ischemia is to first stop the aggravating environmental factors: cold, trauma, smoking, and stress.

"None of the drugs we have is more potent than warm temperatures," the rheumatologist stressed.

Dr. Wigley puts the patient on amlodipine along with aspirin at 81 mg/day, aimed at preventing vascular occlusion. If the patient remains severely ischemic despite maximum-dose amlodipine or has digital ulcers he adds a second vasodilator, typically a phosphodiesterase inhibitor such as sildenafil, which has been shown to reduce the frequency and duration of Raynaud's attacks compared to placebo in a small, double-blind, crossover, randomized trial (Circulation 2005;112:2980-5).

He said he has a low threshold for putting Raynaud's patients on statin therapy as a vascular protection strategy. Dr. Wigley said that he was favorably impressed by findings from a randomized trial in which scleroderma patients placed on atorvastatin at 40 mg/day had a significant decrease in new ulcers compared to placebo, as well as better scores on pain scales and improved endothelial markers (J. Rheumatol. 2008;35:1801-9).

Dr. Wigley declared that he receives consulting fees and/or research grants from Actelion, Amira, Kinemed, Medimmune, Novartis, Orion, Pfizer, and United Therapeutics.

SNOWMASS, Colo. - Until further testing confirms or disproves the promise of an oral formulation of treprostinil that is making its way through the developmental pipeline for management of Raynaud's phenomenon and the ischemic finger, physicians will have to continue to make do with modestly efficacious agents that all are best employed in conjunction with background therapy using a long-acting calcium channel blocker titrated to the maximum tolerated dose.

Calling the developmental oral treprostinil agent particularly exciting, Dr. Frederick M. Wigley noted that the prostacyclin analogs are highly effective in cases of Raynaud's with severe digital ischemia, but the ones available now have to be given intravenously, which is costly and inconvenient.

An effective oral prostacyclin would be a major development. The early clinical trials of oral treprostinil have been quite promising, and the drug is now moving into advanced trials for Raynaud's phenomenon as well as for pulmonary arterial hypertension, according to Dr. Wigley, professor of medicine and director of the scleroderma center at Johns Hopkins University, Baltimore.

However, for now, "the kingpin of our therapy is usually the calcium channel blocker," he observed at a symposium sponsored by the American College of Rheumatology.

He highlighted the agents variously prescribed for Raynaud's and how they fit into his management strategy – and in some cases, why they do not.

His first-line drug for Raynaud's and the ischemic finger is amlodipine, at a starting dose of 5 mg that is titrated to 20 mg/day. This typically results in a 35%-40% reduction in patient-rated symptom severity scores, which he characterized as "a modest benefit." In addition, full-dose calcium channel blocker therapy also appears to reduce the incidence of digital ulcers, in Dr. Wigley's experience.

Other medications often used for Raynaud's phenomenon include:

• Topical nitrates: This popular therapy improves blood flow in affected fingers, but at the price of headaches and other side effects that many patients find intolerable.

"In my practice, I generally use topical nitrates when I have a patient with one finger that's in trouble and I'm trying to get a bit of blush to the surface of the skin. It's a therapy that's generally not tolerated when used on a daily basis on all the fingers," the rheumatologist said.

• Other topicals: EMLA cream (2.5% lidocaine/2.5% prilocaine in a eutectic mixture) provides numbing as well as vasodilation. "I use it often in patients who have painful fingertips. It's probably not quite as potent as the topical nitrates," Dr. Wigley said.

Several studies have shown that topical minoxidil is ineffective. Topical niacin is helpful in bringing a blush to ischemic skin, but it doesn't address deeper ischemic events.

• ACE inhibitors and angiotensin receptor blockers: ACE inhibitors are famously effective in preventing fatal renal crisis in scleroderma patients, but they don't reduce the frequency or severity of Raynaud's episodes, as was demonstrated in a large, randomized, double-blind clinical trial (Arthritis Rheum. 2007;56:3837-46).

In contrast, the angiotensin receptor blocker losartan at 50 mg/day has been shown in a randomized trial to be an effective alternative to calcium channel blocker therapy (Arthritis Rheum. 1999;42:2646-55). However, Dr. Wigley said his own clinical experience has been that losartan's benefits are milder than with a long-acting calcium channel blocker pushed to the maximum tolerated dose.

• Selective serotonin reuptake inhibitors: Activated platelets in Raynaud’s release serotonin, a vasoconstrictor. In a 53-patient randomized, crossover trial, fluoxetine (Prozac) at 20 mg/day resulted in greater reductions in the frequency, duration, and severity of Raynaud's attacks compared to baseline than did nifedipine at 40 mg/day (Rheumatology 2001;40:1038-43).

• Alpha adrenergic blockers: Prazosin was once a very popular treatment, but it has given way to the long-acting calcium channel blockers, which are more effective. Prazosin is primarily an alpha-1 inhibitor, and there aren't a lot of alpha-1 receptors on vascular smooth muscle cells. The alpha-2C receptor is the key player at that site. Selective alpha-2C receptor inhibitors are in development.

• Phosphodiesterase inhibitors: "I must say that I'm generally disappointed with these drugs, and when I use them I do so in conjunction with a calcium channel blocker for their best benefit," Dr. Wigley said.

• Prostaglandins: A Cochrane review of seven clinical trials in patients with Raynaud's phenomenon and scleroderma concluded that prostacyclin analogs reduced attack frequency and severity, improved digital lesions, and resulted in favorable physician assessments of treatment outcome (Cochrane Database of Syst. Rev. 1998;2:CD000953).

European physicians have pioneered cyclic therapy with intravenous iloprost in patients with severe Raynaud's, giving it daily, weekly, or monthly during the winter months and less frequently as needed during warmer weather. Dr. Wigley said that he utilizes intravenous epoprostenol as a key part of his approach to patients with an acute digital ischemic crisis.

• Botulinum toxin type A: Vascular surgeons report glowing results, with rapid improvement after injection of Botox at the base of the finger. But there have been no controlled trials and Dr. Wigley said that he remains skeptical, having used it in a critical situation, with a disappointing lack of acute vasodilation.

"I don't know if it really works or not. We'll have to wait for a good study," he said.

• Bosentan: In the Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess the Effect of Bosentan on Healing and Prevention of Ischemic Digital Ulcers in Patients With Systemic Sclerosis (RAPIDS-1) trial, patients treated with the endothelin inhibitor had a 48% decrease in new ulcers compared to placebo during a 16-week period. They also experienced significantly improved hand function, although there was no benefit in terms of healing of existing ulcers or patient-assessed Raynaud's severity (Arthritis Rheum. 2004;50:3985-93). These findings suggest bosentan may have a role in a protective strategy aimed at reducing ischemic events, according to Dr. Wigley.

• Antioxidants: Most studies have been negative.

At the Johns Hopkins scleroderma center, the management approach taken in a new patient with Raynaud’s phenomenon with digital ischemia is to first stop the aggravating environmental factors: cold, trauma, smoking, and stress.

"None of the drugs we have is more potent than warm temperatures," the rheumatologist stressed.

Dr. Wigley puts the patient on amlodipine along with aspirin at 81 mg/day, aimed at preventing vascular occlusion. If the patient remains severely ischemic despite maximum-dose amlodipine or has digital ulcers he adds a second vasodilator, typically a phosphodiesterase inhibitor such as sildenafil, which has been shown to reduce the frequency and duration of Raynaud's attacks compared to placebo in a small, double-blind, crossover, randomized trial (Circulation 2005;112:2980-5).

He said he has a low threshold for putting Raynaud's patients on statin therapy as a vascular protection strategy. Dr. Wigley said that he was favorably impressed by findings from a randomized trial in which scleroderma patients placed on atorvastatin at 40 mg/day had a significant decrease in new ulcers compared to placebo, as well as better scores on pain scales and improved endothelial markers (J. Rheumatol. 2008;35:1801-9).

Dr. Wigley declared that he receives consulting fees and/or research grants from Actelion, Amira, Kinemed, Medimmune, Novartis, Orion, Pfizer, and United Therapeutics.

SNOWMASS, Colo. – Until further testing confirms or disproves the promise of an oral formulation of treprostinil that is making its way through the developmental pipeline for management of Raynaud’s phenomenon and the ischemic finger, rheumatologists will have to continue to make do with modestly efficacious agents that all are best employed in conjunction with background therapy using a long-acting calcium channel blocker titrated to the maximum tolerated dose.

Calling the developmental oral treprostinil agent particularly exciting, Dr. Frederick M. Wigley noted that the prostacyclin analogs are highly effective in cases of Raynaud’s with severe digital ischemia, but the ones available now have to be given intravenously, which is costly and inconvenient.

An effective oral prostacyclin would be a major development. The early clinical trials of oral treprostinil have been quite promising, and the drug is now moving into advanced trials for Raynaud’s phenomenon as well as for pulmonary arterial hypertension, according to Dr. Wigley, professor of medicine and director of the scleroderma center at Johns Hopkins University, Baltimore.

However, for now, "the kingpin of our therapy is usually the calcium channel blocker," he observed at a symposium sponsored by the American College of Rheumatology.

He highlighted the agents variously prescribed for Raynaud’s and how they fit into his management strategy – and in some cases, why they do not.

His first-line drug for Raynaud’s and the ischemic finger is amlodipine, at a starting dose of 5 mg that is titrated to 20 mg/day. This typically results in a 35%-40% reduction in patient-rated symptom severity scores, which he characterized as "a modest benefit." In addition, full-dose calcium channel blocker therapy also appears to reduce the incidence of digital ulcers, in Dr. Wigley’s experience.

Other medications often used for Raynaud’s phenomenon include:

• Topical nitrates: This popular therapy improves blood flow in affected fingers, but at the price of headaches and other side effects that many patients find intolerable.

"In my practice, I generally use topical nitrates when I have a patient with one finger that’s in trouble and I’m trying to get a bit of blush to the surface of the skin. It’s a therapy that’s generally not tolerated when used on a daily basis on all the fingers," the rheumatologist said.

• Other topicals: EMLA cream (2.5% lidocaine/2.5% prilocaine in a eutectic mixture) provides numbing as well as vasodilation. "I use it often in patients who have painful fingertips. It’s probably not quite as potent as the topical nitrates," Dr. Wigley said.

Several studies have shown that topical minoxidil is ineffective. Topical niacin is helpful in bringing a blush to ischemic skin, but it doesn’t address deeper ischemic events.

• ACE inhibitors and angiotensin-receptor blockers: ACE inhibitors are famously effective in preventing fatal renal crisis in scleroderma patients, but they don’t reduce the frequency or severity of Raynaud’s episodes, as was demonstrated in a large, randomized, double-blind clinical trial (Arthritis Rheum. 2007;56:3837-46).

In contrast, the angiotensin receptor blocker losartan at 50 mg/day has been shown in a randomized trial to be an effective alternative to calcium channel blocker therapy (Arthritis Rheum. 1999;42:2646-55). However, Dr. Wigley said his own clinical experience has been that losartan’s benefits are milder than with a long-acting calcium channel blocker pushed to the maximum tolerated dose.

• Selective serotonin reuptake inhibitors: Activated platelets in Raynaud’s release serotonin, a vasoconstrictor. In a 53-patient randomized, crossover trial, fluoxetine (Prozac) at 20 mg/day resulted in greater reductions in the frequency, duration, and severity of Raynaud’s attacks compared to baseline than did nifedipine at 40 mg/day (Rheumatology 2001;40:1038-43).

• Alpha adrenergic blockers: Prazosin was once a very popular treatment, but it has given way to the long-acting calcium channel blockers, which are more effective. Prazosin is primarily an alpha-1 inhibitor, and there aren’t a lot of alpha-1 receptors on vascular smooth muscle cells. The alpha-2C receptor is the key player at that site. Selective alpha-2C receptor inhibitors are in development.

• Phosphodiesterase inhibitors: "I must say that I’m generally disappointed with these drugs, and when I use them I do so in conjunction with a calcium channel blocker for their best benefit," Dr. Wigley said.

• Prostaglandins: A Cochrane review of seven clinical trials in patients with Raynaud’s phenomenon and scleroderma concluded that prostacyclin analogs reduced attack frequency and severity, improved digital lesions, and resulted in favorable physician assessments of treatment outcome (Cochrane Database of Syst. Rev., 1998, Issue 2, Art. No. CD000953).

European physicians have pioneered cyclic therapy with intravenous iloprost in patients with severe Raynaud’s, giving it daily, weekly, or monthly during the winter months and less frequently as needed during warmer weather. Dr. Wigley said that he utilizes intravenous epoprostenol as a key part of his approach to patients with an acute digital ischemic crisis.

• Botulinum toxin type A: Vascular surgeons report glowing results, with rapid improvement after injection of Botox at the base of the finger. But there have been no controlled trials and Dr. Wigley said that he remains skeptical, having used it in a critical situation, with a disappointing lack of acute vasodilation.

"I don’t know if it really works or not. We’ll have to wait for a good study," he said.

• Bosentan: In the Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess the Effect of Bosentan on Healing and Prevention of Ischemic Digital Ulcers in Patients With Systemic Sclerosis (RAPIDS-1) trial, patients treated with the endothelin inhibitor had a 48% decrease in new ulcers compared to placebo during a 16-week period. They also experienced significantly improved hand function, although there was no benefit in terms of healing of existing ulcers or patient-assessed Raynaud’s severity (Arthritis Rheum. 2004;50:3985-93). These findings suggest bosentan may have a role in a protective strategy aimed at reducing ischemic events, according to Dr. Wigley.

• Antioxidants: Most studies have been negative.

At the Johns Hopkins scleroderma center, the management approach taken in a new patient with Raynaud’s phenomenon with digital ischemia is to first stop the aggravating environmental factors: cold, trauma, smoking, and stress.

"None of the drugs we have is more potent than warm temperatures," the rheumatologist stressed.

Dr. Wigley puts the patient on amlodipine along with aspirin at 81 mg/day, aimed at preventing vascular occlusion. If the patient remains severely ischemic despite maximum-dose amlodipine or has digital ulcers he adds a second vasodilator, typically a phosphodiesterase inhibitor such as sildenafil, which has been shown to reduce the frequency and duration of Raynaud’s attacks compared to placebo in a small, double-blind, crossover, randomized trial (Circulation 2005;112:2980-5).

He said he has a low threshold for putting Raynaud’s patients on statin therapy as a vascular protection strategy. Dr. Wigley said that he was favorably impressed by findings from a randomized trial in which scleroderma patients placed on atorvastatin at 40 mg/day had a significant decrease in new ulcers compared to placebo, as well as better scores on pain scales and improved endothelial markers (J. Rheumatol. 2008;35:1801-9).

Dr. Wigley declared that he receives consulting fees and/or research grants from Actelion, Amira, Kinemed, Medimmune, Novartis, Orion, Pfizer, and United Therapeutics.

SNOWMASS, Colo. – Until further testing confirms or disproves the promise of an oral formulation of treprostinil that is making its way through the developmental pipeline for management of Raynaud’s phenomenon and the ischemic finger, rheumatologists will have to continue to make do with modestly efficacious agents that all are best employed in conjunction with background therapy using a long-acting calcium channel blocker titrated to the maximum tolerated dose.

Calling the developmental oral treprostinil agent particularly exciting, Dr. Frederick M. Wigley noted that the prostacyclin analogs are highly effective in cases of Raynaud’s with severe digital ischemia, but the ones available now have to be given intravenously, which is costly and inconvenient.

An effective oral prostacyclin would be a major development. The early clinical trials of oral treprostinil have been quite promising, and the drug is now moving into advanced trials for Raynaud’s phenomenon as well as for pulmonary arterial hypertension, according to Dr. Wigley, professor of medicine and director of the scleroderma center at Johns Hopkins University, Baltimore.

However, for now, "the kingpin of our therapy is usually the calcium channel blocker," he observed at a symposium sponsored by the American College of Rheumatology.

He highlighted the agents variously prescribed for Raynaud’s and how they fit into his management strategy – and in some cases, why they do not.

His first-line drug for Raynaud’s and the ischemic finger is amlodipine, at a starting dose of 5 mg that is titrated to 20 mg/day. This typically results in a 35%-40% reduction in patient-rated symptom severity scores, which he characterized as "a modest benefit." In addition, full-dose calcium channel blocker therapy also appears to reduce the incidence of digital ulcers, in Dr. Wigley’s experience.

Other medications often used for Raynaud’s phenomenon include:

• Topical nitrates: This popular therapy improves blood flow in affected fingers, but at the price of headaches and other side effects that many patients find intolerable.

"In my practice, I generally use topical nitrates when I have a patient with one finger that’s in trouble and I’m trying to get a bit of blush to the surface of the skin. It’s a therapy that’s generally not tolerated when used on a daily basis on all the fingers," the rheumatologist said.

• Other topicals: EMLA cream (2.5% lidocaine/2.5% prilocaine in a eutectic mixture) provides numbing as well as vasodilation. "I use it often in patients who have painful fingertips. It’s probably not quite as potent as the topical nitrates," Dr. Wigley said.

Several studies have shown that topical minoxidil is ineffective. Topical niacin is helpful in bringing a blush to ischemic skin, but it doesn’t address deeper ischemic events.

• ACE inhibitors and angiotensin-receptor blockers: ACE inhibitors are famously effective in preventing fatal renal crisis in scleroderma patients, but they don’t reduce the frequency or severity of Raynaud’s episodes, as was demonstrated in a large, randomized, double-blind clinical trial (Arthritis Rheum. 2007;56:3837-46).

In contrast, the angiotensin receptor blocker losartan at 50 mg/day has been shown in a randomized trial to be an effective alternative to calcium channel blocker therapy (Arthritis Rheum. 1999;42:2646-55). However, Dr. Wigley said his own clinical experience has been that losartan’s benefits are milder than with a long-acting calcium channel blocker pushed to the maximum tolerated dose.

• Selective serotonin reuptake inhibitors: Activated platelets in Raynaud’s release serotonin, a vasoconstrictor. In a 53-patient randomized, crossover trial, fluoxetine (Prozac) at 20 mg/day resulted in greater reductions in the frequency, duration, and severity of Raynaud’s attacks compared to baseline than did nifedipine at 40 mg/day (Rheumatology 2001;40:1038-43).

• Alpha adrenergic blockers: Prazosin was once a very popular treatment, but it has given way to the long-acting calcium channel blockers, which are more effective. Prazosin is primarily an alpha-1 inhibitor, and there aren’t a lot of alpha-1 receptors on vascular smooth muscle cells. The alpha-2C receptor is the key player at that site. Selective alpha-2C receptor inhibitors are in development.

• Phosphodiesterase inhibitors: "I must say that I’m generally disappointed with these drugs, and when I use them I do so in conjunction with a calcium channel blocker for their best benefit," Dr. Wigley said.

• Prostaglandins: A Cochrane review of seven clinical trials in patients with Raynaud’s phenomenon and scleroderma concluded that prostacyclin analogs reduced attack frequency and severity, improved digital lesions, and resulted in favorable physician assessments of treatment outcome (Cochrane Database of Syst. Rev., 1998, Issue 2, Art. No. CD000953).

European physicians have pioneered cyclic therapy with intravenous iloprost in patients with severe Raynaud’s, giving it daily, weekly, or monthly during the winter months and less frequently as needed during warmer weather. Dr. Wigley said that he utilizes intravenous epoprostenol as a key part of his approach to patients with an acute digital ischemic crisis.

• Botulinum toxin type A: Vascular surgeons report glowing results, with rapid improvement after injection of Botox at the base of the finger. But there have been no controlled trials and Dr. Wigley said that he remains skeptical, having used it in a critical situation, with a disappointing lack of acute vasodilation.

"I don’t know if it really works or not. We’ll have to wait for a good study," he said.

• Bosentan: In the Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess the Effect of Bosentan on Healing and Prevention of Ischemic Digital Ulcers in Patients With Systemic Sclerosis (RAPIDS-1) trial, patients treated with the endothelin inhibitor had a 48% decrease in new ulcers compared to placebo during a 16-week period. They also experienced significantly improved hand function, although there was no benefit in terms of healing of existing ulcers or patient-assessed Raynaud’s severity (Arthritis Rheum. 2004;50:3985-93). These findings suggest bosentan may have a role in a protective strategy aimed at reducing ischemic events, according to Dr. Wigley.

• Antioxidants: Most studies have been negative.

At the Johns Hopkins scleroderma center, the management approach taken in a new patient with Raynaud’s phenomenon with digital ischemia is to first stop the aggravating environmental factors: cold, trauma, smoking, and stress.

"None of the drugs we have is more potent than warm temperatures," the rheumatologist stressed.

Dr. Wigley puts the patient on amlodipine along with aspirin at 81 mg/day, aimed at preventing vascular occlusion. If the patient remains severely ischemic despite maximum-dose amlodipine or has digital ulcers he adds a second vasodilator, typically a phosphodiesterase inhibitor such as sildenafil, which has been shown to reduce the frequency and duration of Raynaud’s attacks compared to placebo in a small, double-blind, crossover, randomized trial (Circulation 2005;112:2980-5).

He said he has a low threshold for putting Raynaud’s patients on statin therapy as a vascular protection strategy. Dr. Wigley said that he was favorably impressed by findings from a randomized trial in which scleroderma patients placed on atorvastatin at 40 mg/day had a significant decrease in new ulcers compared to placebo, as well as better scores on pain scales and improved endothelial markers (J. Rheumatol. 2008;35:1801-9).

Dr. Wigley declared that he receives consulting fees and/or research grants from Actelion, Amira, Kinemed, Medimmune, Novartis, Orion, Pfizer, and United Therapeutics.

SNOWMASS, Colo. – Until further testing confirms or disproves the promise of an oral formulation of treprostinil that is making its way through the developmental pipeline for management of Raynaud’s phenomenon and the ischemic finger, rheumatologists will have to continue to make do with modestly efficacious agents that all are best employed in conjunction with background therapy using a long-acting calcium channel blocker titrated to the maximum tolerated dose.

Calling the developmental oral treprostinil agent particularly exciting, Dr. Frederick M. Wigley noted that the prostacyclin analogs are highly effective in cases of Raynaud’s with severe digital ischemia, but the ones available now have to be given intravenously, which is costly and inconvenient.

An effective oral prostacyclin would be a major development. The early clinical trials of oral treprostinil have been quite promising, and the drug is now moving into advanced trials for Raynaud’s phenomenon as well as for pulmonary arterial hypertension, according to Dr. Wigley, professor of medicine and director of the scleroderma center at Johns Hopkins University, Baltimore.

However, for now, "the kingpin of our therapy is usually the calcium channel blocker," he observed at a symposium sponsored by the American College of Rheumatology.

He highlighted the agents variously prescribed for Raynaud’s and how they fit into his management strategy – and in some cases, why they do not.

His first-line drug for Raynaud’s and the ischemic finger is amlodipine, at a starting dose of 5 mg that is titrated to 20 mg/day. This typically results in a 35%-40% reduction in patient-rated symptom severity scores, which he characterized as "a modest benefit." In addition, full-dose calcium channel blocker therapy also appears to reduce the incidence of digital ulcers, in Dr. Wigley’s experience.

Other medications often used for Raynaud’s phenomenon include:

• Topical nitrates: This popular therapy improves blood flow in affected fingers, but at the price of headaches and other side effects that many patients find intolerable.

"In my practice, I generally use topical nitrates when I have a patient with one finger that’s in trouble and I’m trying to get a bit of blush to the surface of the skin. It’s a therapy that’s generally not tolerated when used on a daily basis on all the fingers," the rheumatologist said.

• Other topicals: EMLA cream (2.5% lidocaine/2.5% prilocaine in a eutectic mixture) provides numbing as well as vasodilation. "I use it often in patients who have painful fingertips. It’s probably not quite as potent as the topical nitrates," Dr. Wigley said.

Several studies have shown that topical minoxidil is ineffective. Topical niacin is helpful in bringing a blush to ischemic skin, but it doesn’t address deeper ischemic events.

• ACE inhibitors and angiotensin-receptor blockers: ACE inhibitors are famously effective in preventing fatal renal crisis in scleroderma patients, but they don’t reduce the frequency or severity of Raynaud’s episodes, as was demonstrated in a large, randomized, double-blind clinical trial (Arthritis Rheum. 2007;56:3837-46).

In contrast, the angiotensin receptor blocker losartan at 50 mg/day has been shown in a randomized trial to be an effective alternative to calcium channel blocker therapy (Arthritis Rheum. 1999;42:2646-55). However, Dr. Wigley said his own clinical experience has been that losartan’s benefits are milder than with a long-acting calcium channel blocker pushed to the maximum tolerated dose.

• Selective serotonin reuptake inhibitors: Activated platelets in Raynaud’s release serotonin, a vasoconstrictor. In a 53-patient randomized, crossover trial, fluoxetine (Prozac) at 20 mg/day resulted in greater reductions in the frequency, duration, and severity of Raynaud’s attacks compared to baseline than did nifedipine at 40 mg/day (Rheumatology 2001;40:1038-43).

• Alpha adrenergic blockers: Prazosin was once a very popular treatment, but it has given way to the long-acting calcium channel blockers, which are more effective. Prazosin is primarily an alpha-1 inhibitor, and there aren’t a lot of alpha-1 receptors on vascular smooth muscle cells. The alpha-2C receptor is the key player at that site. Selective alpha-2C receptor inhibitors are in development.

• Phosphodiesterase inhibitors: "I must say that I’m generally disappointed with these drugs, and when I use them I do so in conjunction with a calcium channel blocker for their best benefit," Dr. Wigley said.

• Prostaglandins: A Cochrane review of seven clinical trials in patients with Raynaud’s phenomenon and scleroderma concluded that prostacyclin analogs reduced attack frequency and severity, improved digital lesions, and resulted in favorable physician assessments of treatment outcome (Cochrane Database of Syst. Rev., 1998, Issue 2, Art. No. CD000953).

European physicians have pioneered cyclic therapy with intravenous iloprost in patients with severe Raynaud’s, giving it daily, weekly, or monthly during the winter months and less frequently as needed during warmer weather. Dr. Wigley said that he utilizes intravenous epoprostenol as a key part of his approach to patients with an acute digital ischemic crisis.

• Botulinum toxin type A: Vascular surgeons report glowing results, with rapid improvement after injection of Botox at the base of the finger. But there have been no controlled trials and Dr. Wigley said that he remains skeptical, having used it in a critical situation, with a disappointing lack of acute vasodilation.

"I don’t know if it really works or not. We’ll have to wait for a good study," he said.

• Bosentan: In the Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess the Effect of Bosentan on Healing and Prevention of Ischemic Digital Ulcers in Patients With Systemic Sclerosis (RAPIDS-1) trial, patients treated with the endothelin inhibitor had a 48% decrease in new ulcers compared to placebo during a 16-week period. They also experienced significantly improved hand function, although there was no benefit in terms of healing of existing ulcers or patient-assessed Raynaud’s severity (Arthritis Rheum. 2004;50:3985-93). These findings suggest bosentan may have a role in a protective strategy aimed at reducing ischemic events, according to Dr. Wigley.

• Antioxidants: Most studies have been negative.

At the Johns Hopkins scleroderma center, the management approach taken in a new patient with Raynaud’s phenomenon with digital ischemia is to first stop the aggravating environmental factors: cold, trauma, smoking, and stress.

"None of the drugs we have is more potent than warm temperatures," the rheumatologist stressed.

Dr. Wigley puts the patient on amlodipine along with aspirin at 81 mg/day, aimed at preventing vascular occlusion. If the patient remains severely ischemic despite maximum-dose amlodipine or has digital ulcers he adds a second vasodilator, typically a phosphodiesterase inhibitor such as sildenafil, which has been shown to reduce the frequency and duration of Raynaud’s attacks compared to placebo in a small, double-blind, crossover, randomized trial (Circulation 2005;112:2980-5).

He said he has a low threshold for putting Raynaud’s patients on statin therapy as a vascular protection strategy. Dr. Wigley said that he was favorably impressed by findings from a randomized trial in which scleroderma patients placed on atorvastatin at 40 mg/day had a significant decrease in new ulcers compared to placebo, as well as better scores on pain scales and improved endothelial markers (J. Rheumatol. 2008;35:1801-9).

Dr. Wigley declared that he receives consulting fees and/or research grants from Actelion, Amira, Kinemed, Medimmune, Novartis, Orion, Pfizer, and United Therapeutics.

CHICAGO - Chronic obstructive pulmonary disease is a powerful risk factor for in-hospital mortality or cardiogenic shock in patients presenting with ST-elevation MI, according to a large retrospective study.

The clinical inference is that the reduced cardiopulmonary reserve imposed by COPD – a disease often marked by pulmonary hypertension and right ventricular dysfunction – renders the circulatory system less capable of coping with the effects of an MI, Dr. Kohei Wakabayashi said at the annual scientific sessions of the American Heart Association.

In a series of 3,249 patients who underwent emergent percutaneous coronary intervention for STEMI at Washington (D.C.) Hospital Center, 365 were known to have COPD. Their rate of in-hospital mortality or cardiogenic shock (24%) was substantially greater than in patients with no COPD (14%).

Patients with COPD were significantly older, were more often smokers and women, and had a higher prevalence of chronic renal insufficiency, hypertension, and diabetes. In a multivariate logistic regression analysis adjusted for these factors, COPD emerged as the single strongest independent predictor of in-hospital mortality or cardiogenic shock in patients undergoing PCI for STEMI, with an associated 83% increased risk.

The other independent predictors of in-hospital mortality or cardiogenic shock in STEMI patients were the number of diseased vessels, maximum creatine kinase value, and age, according to Dr. Wakabayashi of the center.

He declared having no relevant financial interests.

CHICAGO - Chronic obstructive pulmonary disease is a powerful risk factor for in-hospital mortality or cardiogenic shock in patients presenting with ST-elevation MI, according to a large retrospective study.

The clinical inference is that the reduced cardiopulmonary reserve imposed by COPD – a disease often marked by pulmonary hypertension and right ventricular dysfunction – renders the circulatory system less capable of coping with the effects of an MI, Dr. Kohei Wakabayashi said at the annual scientific sessions of the American Heart Association.

In a series of 3,249 patients who underwent emergent percutaneous coronary intervention for STEMI at Washington (D.C.) Hospital Center, 365 were known to have COPD. Their rate of in-hospital mortality or cardiogenic shock (24%) was substantially greater than in patients with no COPD (14%).

Patients with COPD were significantly older, were more often smokers and women, and had a higher prevalence of chronic renal insufficiency, hypertension, and diabetes. In a multivariate logistic regression analysis adjusted for these factors, COPD emerged as the single strongest independent predictor of in-hospital mortality or cardiogenic shock in patients undergoing PCI for STEMI, with an associated 83% increased risk.

The other independent predictors of in-hospital mortality or cardiogenic shock in STEMI patients were the number of diseased vessels, maximum creatine kinase value, and age, according to Dr. Wakabayashi of the center.

He declared having no relevant financial interests.

CHICAGO - Chronic obstructive pulmonary disease is a powerful risk factor for in-hospital mortality or cardiogenic shock in patients presenting with ST-elevation MI, according to a large retrospective study.

The clinical inference is that the reduced cardiopulmonary reserve imposed by COPD – a disease often marked by pulmonary hypertension and right ventricular dysfunction – renders the circulatory system less capable of coping with the effects of an MI, Dr. Kohei Wakabayashi said at the annual scientific sessions of the American Heart Association.

In a series of 3,249 patients who underwent emergent percutaneous coronary intervention for STEMI at Washington (D.C.) Hospital Center, 365 were known to have COPD. Their rate of in-hospital mortality or cardiogenic shock (24%) was substantially greater than in patients with no COPD (14%).

Patients with COPD were significantly older, were more often smokers and women, and had a higher prevalence of chronic renal insufficiency, hypertension, and diabetes. In a multivariate logistic regression analysis adjusted for these factors, COPD emerged as the single strongest independent predictor of in-hospital mortality or cardiogenic shock in patients undergoing PCI for STEMI, with an associated 83% increased risk.

The other independent predictors of in-hospital mortality or cardiogenic shock in STEMI patients were the number of diseased vessels, maximum creatine kinase value, and age, according to Dr. Wakabayashi of the center.

He declared having no relevant financial interests.

CHICAGO – Acute coronary syndrome patients randomized to dual antiplatelet therapy with ticagrelor and aspirin had fewer hospital bed days, revascularization procedures, and total health care costs over the course of 1 year, compared with patients assigned to clopidogrel plus aspirin, according to an economic substudy of the Platelet Inhibition and Patient Outcomes trial.

Mean 1-year total health care costs, excluding the cost of the drugs, were $18,666 in the clopidogrel (Plavix) arm and $17,988 with ticagrelor (Brilinta), an investigational, reversibly binding, oral P2Y12 receptor antagonist, based on Swedish costs per resource used. The resultant mean $678 savings in the ticagrelor group was significant, Dr. Magnus Janzon said at the annual scientific sessions of the American Heart Association.

The Platelet Inhibition and Patient Outcomes (PLATO) trial was a 43-country, double-blind randomized trial of 18,624 patients with acute coronary syndrome. The previously reported primary composite study end point consisting of MI, stroke, or death due to vascular causes occurred in 9.8% of patients in the ticagrelor arm and 11.7% with clopidogrel, for a significant 16% relative risk reduction favoring the newer agent (N. Engl. J. Med. 2009;361:1045-57). This benefit came without any significant cost in terms of major bleeding rates, which were similar in the two treatment arms, noted Dr. Janzon, head of cardiology at Linkoping (Sweden) University Hospital.

The economic substudy included the 10,686 PLATO participants with detailed 1-year follow-up data. During that time frame, the ticagrelor group collectively had 1,149 fewer hospital bed days, including 333 fewer days in the intensive care unit and 379 fewer days in the coronary care unit. The ticagrelor group also had 95 fewer percutaneous coronary interventions and 41 fewer coronary artery bypass graft procedures.

Because health care costs vary so widely from country to country, Dr. Janzon and his colleagues also calculated the 1-year mean total costs using U.S. values, which were nearly twice as high as in Sweden: $34,938 in the ticagrelor plus aspirin group, compared with $33,961 for clopidogrel plus aspirin, for a $977 reduction per patient in the ticagrelor arm.

In December the Food and Drug Administration declined to approve ticagrelor, and requested additional analyses of PLATO despite an earlier 7-1 vote in favor of approval by the FDA’s Cardiovascular and Renal Drugs Advisory Committee.

The PLATO trial was sponsored by AstraZeneca. Dr. Janzon declared having no relevant financial interests.

CHICAGO – Acute coronary syndrome patients randomized to dual antiplatelet therapy with ticagrelor and aspirin had fewer hospital bed days, revascularization procedures, and total health care costs over the course of 1 year, compared with patients assigned to clopidogrel plus aspirin, according to an economic substudy of the Platelet Inhibition and Patient Outcomes trial.

Mean 1-year total health care costs, excluding the cost of the drugs, were $18,666 in the clopidogrel (Plavix) arm and $17,988 with ticagrelor (Brilinta), an investigational, reversibly binding, oral P2Y12 receptor antagonist, based on Swedish costs per resource used. The resultant mean $678 savings in the ticagrelor group was significant, Dr. Magnus Janzon said at the annual scientific sessions of the American Heart Association.

The Platelet Inhibition and Patient Outcomes (PLATO) trial was a 43-country, double-blind randomized trial of 18,624 patients with acute coronary syndrome. The previously reported primary composite study end point consisting of MI, stroke, or death due to vascular causes occurred in 9.8% of patients in the ticagrelor arm and 11.7% with clopidogrel, for a significant 16% relative risk reduction favoring the newer agent (N. Engl. J. Med. 2009;361:1045-57). This benefit came without any significant cost in terms of major bleeding rates, which were similar in the two treatment arms, noted Dr. Janzon, head of cardiology at Linkoping (Sweden) University Hospital.

The economic substudy included the 10,686 PLATO participants with detailed 1-year follow-up data. During that time frame, the ticagrelor group collectively had 1,149 fewer hospital bed days, including 333 fewer days in the intensive care unit and 379 fewer days in the coronary care unit. The ticagrelor group also had 95 fewer percutaneous coronary interventions and 41 fewer coronary artery bypass graft procedures.

Because health care costs vary so widely from country to country, Dr. Janzon and his colleagues also calculated the 1-year mean total costs using U.S. values, which were nearly twice as high as in Sweden: $34,938 in the ticagrelor plus aspirin group, compared with $33,961 for clopidogrel plus aspirin, for a $977 reduction per patient in the ticagrelor arm.

In December the Food and Drug Administration declined to approve ticagrelor, and requested additional analyses of PLATO despite an earlier 7-1 vote in favor of approval by the FDA’s Cardiovascular and Renal Drugs Advisory Committee.

The PLATO trial was sponsored by AstraZeneca. Dr. Janzon declared having no relevant financial interests.

CHICAGO – Acute coronary syndrome patients randomized to dual antiplatelet therapy with ticagrelor and aspirin had fewer hospital bed days, revascularization procedures, and total health care costs over the course of 1 year, compared with patients assigned to clopidogrel plus aspirin, according to an economic substudy of the Platelet Inhibition and Patient Outcomes trial.

Mean 1-year total health care costs, excluding the cost of the drugs, were $18,666 in the clopidogrel (Plavix) arm and $17,988 with ticagrelor (Brilinta), an investigational, reversibly binding, oral P2Y12 receptor antagonist, based on Swedish costs per resource used. The resultant mean $678 savings in the ticagrelor group was significant, Dr. Magnus Janzon said at the annual scientific sessions of the American Heart Association.

The Platelet Inhibition and Patient Outcomes (PLATO) trial was a 43-country, double-blind randomized trial of 18,624 patients with acute coronary syndrome. The previously reported primary composite study end point consisting of MI, stroke, or death due to vascular causes occurred in 9.8% of patients in the ticagrelor arm and 11.7% with clopidogrel, for a significant 16% relative risk reduction favoring the newer agent (N. Engl. J. Med. 2009;361:1045-57). This benefit came without any significant cost in terms of major bleeding rates, which were similar in the two treatment arms, noted Dr. Janzon, head of cardiology at Linkoping (Sweden) University Hospital.

The economic substudy included the 10,686 PLATO participants with detailed 1-year follow-up data. During that time frame, the ticagrelor group collectively had 1,149 fewer hospital bed days, including 333 fewer days in the intensive care unit and 379 fewer days in the coronary care unit. The ticagrelor group also had 95 fewer percutaneous coronary interventions and 41 fewer coronary artery bypass graft procedures.

Because health care costs vary so widely from country to country, Dr. Janzon and his colleagues also calculated the 1-year mean total costs using U.S. values, which were nearly twice as high as in Sweden: $34,938 in the ticagrelor plus aspirin group, compared with $33,961 for clopidogrel plus aspirin, for a $977 reduction per patient in the ticagrelor arm.

In December the Food and Drug Administration declined to approve ticagrelor, and requested additional analyses of PLATO despite an earlier 7-1 vote in favor of approval by the FDA’s Cardiovascular and Renal Drugs Advisory Committee.

The PLATO trial was sponsored by AstraZeneca. Dr. Janzon declared having no relevant financial interests.