Elizabeth Mechcatie

A move away from specific cholesterol treatment targets, assessment of both 10-year and lifetime cardiovascular disease risk, and inclusion of stroke in cardiovascular disease risk estimates are among the highlights of updated clinical practice guidelines on reducing cardiovascular risk released Nov. 12 by the American College of Cardiology and American Heart Association.

Written by the blood cholesterol expert panel that was originally the Adult Treatment Panel (ATP) IV, the cholesterol treatment guideline will inevitably receive the most attention, with the shift from recommending treatment of cholesterol to a specific LDL cholesterol target to treatment based on an increased risk for cardiovascular disease and stroke with medications proven to reduce those risks.

© ProjectB/iStockphoto.com

"Rather than LDL-C or non–HDL-C targets, this guideline used the intensity of statin therapy as the goal of treatment," identifying four groups of individuals "for whom an extensive body" of evidence from randomized controlled trials demonstrated a reduction in atherosclerotic CVD events "with a good margin of safety from moderate- or high-intensity statin therapy," the panel concluded. While these guidelines are a change from previous guidelines, "clinicians have become accustomed to change when that change is consistent with the current evidence," they added.

The cholesterol treatment guideline provides "a new perspective on LDL and non-HDL treatment goals," with the identification of the four groups of patients for whom moderate- or high-intensity statin treatment is recommended, for primary or secondary prevention, explained Dr. Neil J. Stone, chair of the writing committee. "Despite an extensive review, we were unable to find solid evidence to support continued use of specific LDL-cholesterol or non-HDL treatment targets," he said in a telephone briefing.

The previous guidelines recommended treating to an LDL goal of below 100 mg/dL in people at high cardiovascular risk, but also recommended a goal of 70 mg/dL or lower for patients at very high risk.

The four sets of clinical practice guidelines were initially commissioned by the National Heart, Lung, and Blood Institute (NHLBI) in 2008, and were transitioned to the AHA and ACC earlier this year. On the basis of evidence from the best clinical trials and epidemiologic studies through 2011, the "long-awaited" guidelines focus on assessment of cardiovascular risk, lifestyle modifications to reduce cardiovascular risk, and management of overweight and obesity in adults, in addition to management of blood cholesterol, Dr. John Gordon Harold, ACC president, said during the briefing.

The 2013 guidelines "will provide updated guidance to primary care providers, nurses, pharmacists, and speciality medicine providers on how to best manage care of individuals at risk of cardiovascular diseases," based on evidence available through 2011, said Dr. Harold of the David Geffen School of Medicine at the University of California and Cedars-Sinai Heart Institute, Los Angeles.

Cholesterol treatment

In the cholesterol treatment guideline, Dr. Stone said that based on an extensive literature review, the evidence supported the use of the "appropriate intensity" of statin therapy in addition to a heart-healthy lifestyle to reduce risk, with the identification of four "major statin benefit groups" for whom "high intensity" statin treatment (lowering LDL by at least 50%) or "moderate intensity" statin treatment (lowering LDL by roughly 30%-49%) is recommended. Those groups are patients with:

• Clinical atherosclerotic cardiovascular disease (ASCVD).

• A primary elevation of LDL-cholesterol of 190 mg/dL or higher, including those with familial hypercholesterolemia.

• Diabetes, aged 40-75 years with no clinical ASCVD and LDL levels of 70-189 mg/dL.

• No clinical ASCVD or diabetes, aged 40-75 years, with an LDL of 70-189 mg/dL and an estimated 10-year risk of ASCVD of at least 7.5% (determined by calculating the global cardiovascular risk assessment score, using formulas developed by the Risk Assessment guideline work group and included in that guideline).

"The idea was that certain groups such as those with [a prior atherosclerotic event] and those with very high LDL-cholesterol, especially these familial forms ... benefit most, if they can tolerate it, from high-intensity statin therapy." For those with a score of 7.5% or more, who have not had an MI or stroke, analyses provide strong evidence that treatment can forestall or prevent these events, and in those at high risk, "even can reduce total mortality," said Dr. Stone, Robert Bonow Professor in the division of medicine-cardiology at Northwestern University, Chicago.

Often, the use of a specific target might lead to undertreatment in certain groups, or overtreatment when, for example, additional medications that are not proven to add incremental or additional benefit are added to treatment. Rather than supporting a target, the data indicated that clinicians "use the appropriate intensity of statin therapy to reduce this atherosclerotic risk in those most likely to benefit," and that nonstatin therapies "didn’t provide an acceptable CVD risk reduction benefit compared to their adverse effects in the routine prevention of heart attack and stroke," Dr. Stone noted.

Assessment of cardiovascular risk

The guideline on assessing cardiovascular risk in adults includes the global risk assessment tool, which "provides a quantitative clinical assessment to guide clinical care," said Dr. Donald M. Lloyd-Jones, one of the cochairs in the work group that wrote this guideline.

The guideline recommends lifetime risk alongside 10-year risk, said Dr. Lloyd-Jones, chair and professor of preventive medicine at Northwestern University, Chicago. The 10-year risk equations predict the risk of MI and stroke, while previous risk equations focused only on the risk of coronary heart disease events. "We realized quickly that we were leaving a lot of risk on the table by not also including stroke in our risk assessment algorithm," which is particularly important in female and black patients, he said.

Estimating lifetime risk may be particularly useful for identifying younger patients who have a low 10-year risk "but who have unhealthy lifestyles or risk factors that will put them at substantial risk for developing cardiovascular disease in the longer term," he added.

The risk equations for non-Hispanic white men and women and for black men and women are based on data from NHLBI-funded population-based studies, including the Coronary Artery Risk Development in Young Adults Study (CARDIA), the Atherosclerosis Risk in Communities Study (ARIC), and the Cardiovascular Health Study (CHS), as well as the Framingham Heart Study. These require input of age, sex, race, total and HDL cholesterol levels, blood pressure, blood pressure treatment status, and current smoking and diabetes status, which were identified as the best predictors for 10-year risk, Dr. Lloyd-Jones said.

Other risk markers were considered, but were not included because there was not sufficient information to warrant their inclusion in the equations. Until risk-predictor equations are developed for Hispanics, Latinos, and Asian-Americans, as relevant data become available, the risk equations for white men and women should be used for other races and ethnic groups in the United States, he said.

Based on review of the literature on newer risk markers, the work group determined that four markers "may be considered" in refining risk estimates, if there is uncertainty after performing the risk equations: family history of premature cardiovascular disease in a first degree relative, coronary artery calcium score, measurement of high sensitivity of C-reactive protein (CRP), and measurement of ankle-brachial index. The evidence for using other markers was insufficient, and "we explicitly recommend against performing carotid intimal medial thickness measurement," because of evidence that there is no additional benefit of this test, Dr. Lloyd-Jones said.

The guideline provides information on how to incorporate risk assessment into clinical practice settings, and includes an Excel spreadsheet that can be used to calculate risk, said Dr. Lloyd-Jones. Risk equations can also be programmed into electronic health records.

Dr. John Rumsfeld, acting national director of cardiology for the Veterans Health Administration, views the change in cholesterol treatment recommendations as "a course correction," rather than a radical change in direction. "These guidelines are based on an objective review of the evidence – and that evidence is clear: There is no evidence for treating to specific target numbers for cholesterol. Yet, there is clear and strong evidence for the use of statin medications for people at elevated risk for heart disease and stroke," he said.

"The new treatment approach is more patient centered; it is about treating those who are most likely to benefit from taking a chronic medication; it is about reducing their risk with proven medicines; and it also reduces patient burden by lessening the need for repeat testing and taking additional, unproven medications," he said in an interview.

Over a year ago, the VA health care system dropped its national performance measure for treating to an LDL-cholesterol below 100 mg/dL, based on an independent review of the evidence. Using an approach that is similar to that recommended in the new guideline, the VA implemented a performance measure that emphasized the use of statin medication in patients at elevated risk. "The change from treating targets to treating risk leads to fewer patients being overtreated with unproven medications, and reduces the burden on patients of repeated blood testing and additional medications to take," said Dr. Rumsfeld, also professor of medicine at the University of Colorado, Denver. In addition, the change reduces repeat blood tests and extra medication use, reducing costs to the health care system, he pointed out.

"Instead of repeated laboratory testing, and uptitrating medications or adding additional medications for patients to take with possible side effects, this approach emphasizes initiating treatment with proven medications for those at risk," he said.

Although clinicians may be initially surprised by the guidelines, he said he believes they will be well received. Clinicians "will quickly see that the approach reflects current evidence, and that the approach simplifies care," said Dr. Rumsfeld, who served as one of the expert reviewers of the guidelines.

Lifestyle management to reduce cardiovascular risk

The other two guidelines are on lifestyle management, and on overweight and obesity. The lifestyle management guideline includes recommendations for a dietary patterns that are heart healthy, including those with fruits, vegetables, and whole grains; limiting saturated fat, trans fat, and sodium intake; and for a physical activity level that complements dietary recommendations," said Dr. Robert H. Eckel, cochair of the writing committee, and professor of medicine at the University of Colorado, Denver.

The physical activity recommendations are based largely on a 2008 Department of Health and Human Services report, which provided support for 30-40 minutes of moderate to vigorous activity at least 3-4 days a week. For people who could benefit from a lower blood pressure, the guideline recommends a sodium intake of no more than 2,400 mg per day (a reduction from the current average of about 3,600 mg a day among U.S. adults), but points out that sodium intake of 1,500 mg a day or less has been associated with greater reductions in blood pressure.

Management of overweight and obesity in adults

The guidelines on the management of overweight and obesity in adults, developed with the Obesity Society, provide recommendations in five major areas and include a treatment algorithm on weight management, to help primary care providers address weight management in their patients, said Dr. Donna Ryan, cochair of the writing committee and professor emeritus at Louisiana State University’s Pennington Biomedical Research Center, Baton Rouge.

The guidelines help primary care providers identify which patients need to lose weight and how much weight loss is needed, as well as the benefits of weight loss, the best diet, the effectiveness of lifestyle interventions, and the benefits and risks of bariatric surgery.

The recommendations include the use of body mass index as "a quick and easy first screening step" to identify patients who may be at risk for obesity-related health problems, and weight circumference as an indicator of ASCVD risk, type 2 diabetes, and all-cause mortality, Dr. Ryan said.

Since the ideal weight loss diet has not been identified, providers should recommend a diet that results in reduced caloric intake, and the type of diet "should really be determined by the patient’s preferences and their health status," such as a reduced calorie, reduced sodium diet for an overweight, hypertensive patient. Another recommendation is a comprehensive approach to weight loss that involves diet and physical activity, with counseling for 6 months or more – which ideally should be on-site group or individual counseling sessions with a trained professional for at least 1 year.

Bariatric surgery may be an option for patients with a BMI of 35 kg/m², with comorbidities, or a BMI of 40. Although a "critical" area, recommendations on pharmacotherapy are not included, because at the time the guidelines were being developed, sibutramine (which has since been taken off the market) and orlistat were the only medications approved for weight loss in the United States.

Dr. Stone, Dr. Lloyd-Jones, and Dr. Rumsfeld had no disclosures.

Dr. Eckel disclosed ties to Merck, Pfizer, Abbott, Amylin, Eli Lilly, Esperion, Foodminds, Johnson & Johnson, Novo Nordisk, Vivus, GlaxoSmithKline, and Sanofi-Aventis/Regeneron.

Dr. Ryan disclosed ties to Alere Wellbeing, Amylin, Arena Pharmaceuticals, Eisai, Novo Nordisk, Nutrisystem, Orexigen, Takeda, and Vivus. She is chief medical officer of Scientific Intake.

[email protected]

A move away from specific cholesterol treatment targets, assessment of both 10-year and lifetime cardiovascular disease risk, and inclusion of stroke in cardiovascular disease risk estimates are among the highlights of updated clinical practice guidelines on reducing cardiovascular risk released Nov. 12 by the American College of Cardiology and American Heart Association.

Written by the blood cholesterol expert panel that was originally the Adult Treatment Panel (ATP) IV, the cholesterol treatment guideline will inevitably receive the most attention, with the shift from recommending treatment of cholesterol to a specific LDL cholesterol target to treatment based on an increased risk for cardiovascular disease and stroke with medications proven to reduce those risks.

© ProjectB/iStockphoto.com

"Rather than LDL-C or non–HDL-C targets, this guideline used the intensity of statin therapy as the goal of treatment," identifying four groups of individuals "for whom an extensive body" of evidence from randomized controlled trials demonstrated a reduction in atherosclerotic CVD events "with a good margin of safety from moderate- or high-intensity statin therapy," the panel concluded. While these guidelines are a change from previous guidelines, "clinicians have become accustomed to change when that change is consistent with the current evidence," they added.

The cholesterol treatment guideline provides "a new perspective on LDL and non-HDL treatment goals," with the identification of the four groups of patients for whom moderate- or high-intensity statin treatment is recommended, for primary or secondary prevention, explained Dr. Neil J. Stone, chair of the writing committee. "Despite an extensive review, we were unable to find solid evidence to support continued use of specific LDL-cholesterol or non-HDL treatment targets," he said in a telephone briefing.

The previous guidelines recommended treating to an LDL goal of below 100 mg/dL in people at high cardiovascular risk, but also recommended a goal of 70 mg/dL or lower for patients at very high risk.

The four sets of clinical practice guidelines were initially commissioned by the National Heart, Lung, and Blood Institute (NHLBI) in 2008, and were transitioned to the AHA and ACC earlier this year. On the basis of evidence from the best clinical trials and epidemiologic studies through 2011, the "long-awaited" guidelines focus on assessment of cardiovascular risk, lifestyle modifications to reduce cardiovascular risk, and management of overweight and obesity in adults, in addition to management of blood cholesterol, Dr. John Gordon Harold, ACC president, said during the briefing.

The 2013 guidelines "will provide updated guidance to primary care providers, nurses, pharmacists, and speciality medicine providers on how to best manage care of individuals at risk of cardiovascular diseases," based on evidence available through 2011, said Dr. Harold of the David Geffen School of Medicine at the University of California and Cedars-Sinai Heart Institute, Los Angeles.

Cholesterol treatment

In the cholesterol treatment guideline, Dr. Stone said that based on an extensive literature review, the evidence supported the use of the "appropriate intensity" of statin therapy in addition to a heart-healthy lifestyle to reduce risk, with the identification of four "major statin benefit groups" for whom "high intensity" statin treatment (lowering LDL by at least 50%) or "moderate intensity" statin treatment (lowering LDL by roughly 30%-49%) is recommended. Those groups are patients with:

• Clinical atherosclerotic cardiovascular disease (ASCVD).

• A primary elevation of LDL-cholesterol of 190 mg/dL or higher, including those with familial hypercholesterolemia.

• Diabetes, aged 40-75 years with no clinical ASCVD and LDL levels of 70-189 mg/dL.

• No clinical ASCVD or diabetes, aged 40-75 years, with an LDL of 70-189 mg/dL and an estimated 10-year risk of ASCVD of at least 7.5% (determined by calculating the global cardiovascular risk assessment score, using formulas developed by the Risk Assessment guideline work group and included in that guideline).

"The idea was that certain groups such as those with [a prior atherosclerotic event] and those with very high LDL-cholesterol, especially these familial forms ... benefit most, if they can tolerate it, from high-intensity statin therapy." For those with a score of 7.5% or more, who have not had an MI or stroke, analyses provide strong evidence that treatment can forestall or prevent these events, and in those at high risk, "even can reduce total mortality," said Dr. Stone, Robert Bonow Professor in the division of medicine-cardiology at Northwestern University, Chicago.

Often, the use of a specific target might lead to undertreatment in certain groups, or overtreatment when, for example, additional medications that are not proven to add incremental or additional benefit are added to treatment. Rather than supporting a target, the data indicated that clinicians "use the appropriate intensity of statin therapy to reduce this atherosclerotic risk in those most likely to benefit," and that nonstatin therapies "didn’t provide an acceptable CVD risk reduction benefit compared to their adverse effects in the routine prevention of heart attack and stroke," Dr. Stone noted.

Assessment of cardiovascular risk

The guideline on assessing cardiovascular risk in adults includes the global risk assessment tool, which "provides a quantitative clinical assessment to guide clinical care," said Dr. Donald M. Lloyd-Jones, one of the cochairs in the work group that wrote this guideline.

The guideline recommends lifetime risk alongside 10-year risk, said Dr. Lloyd-Jones, chair and professor of preventive medicine at Northwestern University, Chicago. The 10-year risk equations predict the risk of MI and stroke, while previous risk equations focused only on the risk of coronary heart disease events. "We realized quickly that we were leaving a lot of risk on the table by not also including stroke in our risk assessment algorithm," which is particularly important in female and black patients, he said.

Estimating lifetime risk may be particularly useful for identifying younger patients who have a low 10-year risk "but who have unhealthy lifestyles or risk factors that will put them at substantial risk for developing cardiovascular disease in the longer term," he added.

The risk equations for non-Hispanic white men and women and for black men and women are based on data from NHLBI-funded population-based studies, including the Coronary Artery Risk Development in Young Adults Study (CARDIA), the Atherosclerosis Risk in Communities Study (ARIC), and the Cardiovascular Health Study (CHS), as well as the Framingham Heart Study. These require input of age, sex, race, total and HDL cholesterol levels, blood pressure, blood pressure treatment status, and current smoking and diabetes status, which were identified as the best predictors for 10-year risk, Dr. Lloyd-Jones said.

Other risk markers were considered, but were not included because there was not sufficient information to warrant their inclusion in the equations. Until risk-predictor equations are developed for Hispanics, Latinos, and Asian-Americans, as relevant data become available, the risk equations for white men and women should be used for other races and ethnic groups in the United States, he said.

Based on review of the literature on newer risk markers, the work group determined that four markers "may be considered" in refining risk estimates, if there is uncertainty after performing the risk equations: family history of premature cardiovascular disease in a first degree relative, coronary artery calcium score, measurement of high sensitivity of C-reactive protein (CRP), and measurement of ankle-brachial index. The evidence for using other markers was insufficient, and "we explicitly recommend against performing carotid intimal medial thickness measurement," because of evidence that there is no additional benefit of this test, Dr. Lloyd-Jones said.

The guideline provides information on how to incorporate risk assessment into clinical practice settings, and includes an Excel spreadsheet that can be used to calculate risk, said Dr. Lloyd-Jones. Risk equations can also be programmed into electronic health records.

Dr. John Rumsfeld, acting national director of cardiology for the Veterans Health Administration, views the change in cholesterol treatment recommendations as "a course correction," rather than a radical change in direction. "These guidelines are based on an objective review of the evidence – and that evidence is clear: There is no evidence for treating to specific target numbers for cholesterol. Yet, there is clear and strong evidence for the use of statin medications for people at elevated risk for heart disease and stroke," he said.

"The new treatment approach is more patient centered; it is about treating those who are most likely to benefit from taking a chronic medication; it is about reducing their risk with proven medicines; and it also reduces patient burden by lessening the need for repeat testing and taking additional, unproven medications," he said in an interview.

Over a year ago, the VA health care system dropped its national performance measure for treating to an LDL-cholesterol below 100 mg/dL, based on an independent review of the evidence. Using an approach that is similar to that recommended in the new guideline, the VA implemented a performance measure that emphasized the use of statin medication in patients at elevated risk. "The change from treating targets to treating risk leads to fewer patients being overtreated with unproven medications, and reduces the burden on patients of repeated blood testing and additional medications to take," said Dr. Rumsfeld, also professor of medicine at the University of Colorado, Denver. In addition, the change reduces repeat blood tests and extra medication use, reducing costs to the health care system, he pointed out.

"Instead of repeated laboratory testing, and uptitrating medications or adding additional medications for patients to take with possible side effects, this approach emphasizes initiating treatment with proven medications for those at risk," he said.

Although clinicians may be initially surprised by the guidelines, he said he believes they will be well received. Clinicians "will quickly see that the approach reflects current evidence, and that the approach simplifies care," said Dr. Rumsfeld, who served as one of the expert reviewers of the guidelines.

Lifestyle management to reduce cardiovascular risk

The other two guidelines are on lifestyle management, and on overweight and obesity. The lifestyle management guideline includes recommendations for a dietary patterns that are heart healthy, including those with fruits, vegetables, and whole grains; limiting saturated fat, trans fat, and sodium intake; and for a physical activity level that complements dietary recommendations," said Dr. Robert H. Eckel, cochair of the writing committee, and professor of medicine at the University of Colorado, Denver.

The physical activity recommendations are based largely on a 2008 Department of Health and Human Services report, which provided support for 30-40 minutes of moderate to vigorous activity at least 3-4 days a week. For people who could benefit from a lower blood pressure, the guideline recommends a sodium intake of no more than 2,400 mg per day (a reduction from the current average of about 3,600 mg a day among U.S. adults), but points out that sodium intake of 1,500 mg a day or less has been associated with greater reductions in blood pressure.

Management of overweight and obesity in adults

The guidelines on the management of overweight and obesity in adults, developed with the Obesity Society, provide recommendations in five major areas and include a treatment algorithm on weight management, to help primary care providers address weight management in their patients, said Dr. Donna Ryan, cochair of the writing committee and professor emeritus at Louisiana State University’s Pennington Biomedical Research Center, Baton Rouge.

The guidelines help primary care providers identify which patients need to lose weight and how much weight loss is needed, as well as the benefits of weight loss, the best diet, the effectiveness of lifestyle interventions, and the benefits and risks of bariatric surgery.

The recommendations include the use of body mass index as "a quick and easy first screening step" to identify patients who may be at risk for obesity-related health problems, and weight circumference as an indicator of ASCVD risk, type 2 diabetes, and all-cause mortality, Dr. Ryan said.

Since the ideal weight loss diet has not been identified, providers should recommend a diet that results in reduced caloric intake, and the type of diet "should really be determined by the patient’s preferences and their health status," such as a reduced calorie, reduced sodium diet for an overweight, hypertensive patient. Another recommendation is a comprehensive approach to weight loss that involves diet and physical activity, with counseling for 6 months or more – which ideally should be on-site group or individual counseling sessions with a trained professional for at least 1 year.

Bariatric surgery may be an option for patients with a BMI of 35 kg/m², with comorbidities, or a BMI of 40. Although a "critical" area, recommendations on pharmacotherapy are not included, because at the time the guidelines were being developed, sibutramine (which has since been taken off the market) and orlistat were the only medications approved for weight loss in the United States.

Dr. Stone, Dr. Lloyd-Jones, and Dr. Rumsfeld had no disclosures.

Dr. Eckel disclosed ties to Merck, Pfizer, Abbott, Amylin, Eli Lilly, Esperion, Foodminds, Johnson & Johnson, Novo Nordisk, Vivus, GlaxoSmithKline, and Sanofi-Aventis/Regeneron.

Dr. Ryan disclosed ties to Alere Wellbeing, Amylin, Arena Pharmaceuticals, Eisai, Novo Nordisk, Nutrisystem, Orexigen, Takeda, and Vivus. She is chief medical officer of Scientific Intake.

[email protected]

A move away from specific cholesterol treatment targets, assessment of both 10-year and lifetime cardiovascular disease risk, and inclusion of stroke in cardiovascular disease risk estimates are among the highlights of updated clinical practice guidelines on reducing cardiovascular risk released Nov. 12 by the American College of Cardiology and American Heart Association.

Written by the blood cholesterol expert panel that was originally the Adult Treatment Panel (ATP) IV, the cholesterol treatment guideline will inevitably receive the most attention, with the shift from recommending treatment of cholesterol to a specific LDL cholesterol target to treatment based on an increased risk for cardiovascular disease and stroke with medications proven to reduce those risks.

© ProjectB/iStockphoto.com

"Rather than LDL-C or non–HDL-C targets, this guideline used the intensity of statin therapy as the goal of treatment," identifying four groups of individuals "for whom an extensive body" of evidence from randomized controlled trials demonstrated a reduction in atherosclerotic CVD events "with a good margin of safety from moderate- or high-intensity statin therapy," the panel concluded. While these guidelines are a change from previous guidelines, "clinicians have become accustomed to change when that change is consistent with the current evidence," they added.

The cholesterol treatment guideline provides "a new perspective on LDL and non-HDL treatment goals," with the identification of the four groups of patients for whom moderate- or high-intensity statin treatment is recommended, for primary or secondary prevention, explained Dr. Neil J. Stone, chair of the writing committee. "Despite an extensive review, we were unable to find solid evidence to support continued use of specific LDL-cholesterol or non-HDL treatment targets," he said in a telephone briefing.

The previous guidelines recommended treating to an LDL goal of below 100 mg/dL in people at high cardiovascular risk, but also recommended a goal of 70 mg/dL or lower for patients at very high risk.

The four sets of clinical practice guidelines were initially commissioned by the National Heart, Lung, and Blood Institute (NHLBI) in 2008, and were transitioned to the AHA and ACC earlier this year. On the basis of evidence from the best clinical trials and epidemiologic studies through 2011, the "long-awaited" guidelines focus on assessment of cardiovascular risk, lifestyle modifications to reduce cardiovascular risk, and management of overweight and obesity in adults, in addition to management of blood cholesterol, Dr. John Gordon Harold, ACC president, said during the briefing.

The 2013 guidelines "will provide updated guidance to primary care providers, nurses, pharmacists, and speciality medicine providers on how to best manage care of individuals at risk of cardiovascular diseases," based on evidence available through 2011, said Dr. Harold of the David Geffen School of Medicine at the University of California and Cedars-Sinai Heart Institute, Los Angeles.

Cholesterol treatment

In the cholesterol treatment guideline, Dr. Stone said that based on an extensive literature review, the evidence supported the use of the "appropriate intensity" of statin therapy in addition to a heart-healthy lifestyle to reduce risk, with the identification of four "major statin benefit groups" for whom "high intensity" statin treatment (lowering LDL by at least 50%) or "moderate intensity" statin treatment (lowering LDL by roughly 30%-49%) is recommended. Those groups are patients with:

• Clinical atherosclerotic cardiovascular disease (ASCVD).

• A primary elevation of LDL-cholesterol of 190 mg/dL or higher, including those with familial hypercholesterolemia.

• Diabetes, aged 40-75 years with no clinical ASCVD and LDL levels of 70-189 mg/dL.

• No clinical ASCVD or diabetes, aged 40-75 years, with an LDL of 70-189 mg/dL and an estimated 10-year risk of ASCVD of at least 7.5% (determined by calculating the global cardiovascular risk assessment score, using formulas developed by the Risk Assessment guideline work group and included in that guideline).

"The idea was that certain groups such as those with [a prior atherosclerotic event] and those with very high LDL-cholesterol, especially these familial forms ... benefit most, if they can tolerate it, from high-intensity statin therapy." For those with a score of 7.5% or more, who have not had an MI or stroke, analyses provide strong evidence that treatment can forestall or prevent these events, and in those at high risk, "even can reduce total mortality," said Dr. Stone, Robert Bonow Professor in the division of medicine-cardiology at Northwestern University, Chicago.

Often, the use of a specific target might lead to undertreatment in certain groups, or overtreatment when, for example, additional medications that are not proven to add incremental or additional benefit are added to treatment. Rather than supporting a target, the data indicated that clinicians "use the appropriate intensity of statin therapy to reduce this atherosclerotic risk in those most likely to benefit," and that nonstatin therapies "didn’t provide an acceptable CVD risk reduction benefit compared to their adverse effects in the routine prevention of heart attack and stroke," Dr. Stone noted.

Assessment of cardiovascular risk

The guideline on assessing cardiovascular risk in adults includes the global risk assessment tool, which "provides a quantitative clinical assessment to guide clinical care," said Dr. Donald M. Lloyd-Jones, one of the cochairs in the work group that wrote this guideline.

The guideline recommends lifetime risk alongside 10-year risk, said Dr. Lloyd-Jones, chair and professor of preventive medicine at Northwestern University, Chicago. The 10-year risk equations predict the risk of MI and stroke, while previous risk equations focused only on the risk of coronary heart disease events. "We realized quickly that we were leaving a lot of risk on the table by not also including stroke in our risk assessment algorithm," which is particularly important in female and black patients, he said.

Estimating lifetime risk may be particularly useful for identifying younger patients who have a low 10-year risk "but who have unhealthy lifestyles or risk factors that will put them at substantial risk for developing cardiovascular disease in the longer term," he added.

The risk equations for non-Hispanic white men and women and for black men and women are based on data from NHLBI-funded population-based studies, including the Coronary Artery Risk Development in Young Adults Study (CARDIA), the Atherosclerosis Risk in Communities Study (ARIC), and the Cardiovascular Health Study (CHS), as well as the Framingham Heart Study. These require input of age, sex, race, total and HDL cholesterol levels, blood pressure, blood pressure treatment status, and current smoking and diabetes status, which were identified as the best predictors for 10-year risk, Dr. Lloyd-Jones said.

Other risk markers were considered, but were not included because there was not sufficient information to warrant their inclusion in the equations. Until risk-predictor equations are developed for Hispanics, Latinos, and Asian-Americans, as relevant data become available, the risk equations for white men and women should be used for other races and ethnic groups in the United States, he said.

Based on review of the literature on newer risk markers, the work group determined that four markers "may be considered" in refining risk estimates, if there is uncertainty after performing the risk equations: family history of premature cardiovascular disease in a first degree relative, coronary artery calcium score, measurement of high sensitivity of C-reactive protein (CRP), and measurement of ankle-brachial index. The evidence for using other markers was insufficient, and "we explicitly recommend against performing carotid intimal medial thickness measurement," because of evidence that there is no additional benefit of this test, Dr. Lloyd-Jones said.

The guideline provides information on how to incorporate risk assessment into clinical practice settings, and includes an Excel spreadsheet that can be used to calculate risk, said Dr. Lloyd-Jones. Risk equations can also be programmed into electronic health records.

Dr. John Rumsfeld, acting national director of cardiology for the Veterans Health Administration, views the change in cholesterol treatment recommendations as "a course correction," rather than a radical change in direction. "These guidelines are based on an objective review of the evidence – and that evidence is clear: There is no evidence for treating to specific target numbers for cholesterol. Yet, there is clear and strong evidence for the use of statin medications for people at elevated risk for heart disease and stroke," he said.

"The new treatment approach is more patient centered; it is about treating those who are most likely to benefit from taking a chronic medication; it is about reducing their risk with proven medicines; and it also reduces patient burden by lessening the need for repeat testing and taking additional, unproven medications," he said in an interview.

Over a year ago, the VA health care system dropped its national performance measure for treating to an LDL-cholesterol below 100 mg/dL, based on an independent review of the evidence. Using an approach that is similar to that recommended in the new guideline, the VA implemented a performance measure that emphasized the use of statin medication in patients at elevated risk. "The change from treating targets to treating risk leads to fewer patients being overtreated with unproven medications, and reduces the burden on patients of repeated blood testing and additional medications to take," said Dr. Rumsfeld, also professor of medicine at the University of Colorado, Denver. In addition, the change reduces repeat blood tests and extra medication use, reducing costs to the health care system, he pointed out.

"Instead of repeated laboratory testing, and uptitrating medications or adding additional medications for patients to take with possible side effects, this approach emphasizes initiating treatment with proven medications for those at risk," he said.

Although clinicians may be initially surprised by the guidelines, he said he believes they will be well received. Clinicians "will quickly see that the approach reflects current evidence, and that the approach simplifies care," said Dr. Rumsfeld, who served as one of the expert reviewers of the guidelines.

Lifestyle management to reduce cardiovascular risk

The other two guidelines are on lifestyle management, and on overweight and obesity. The lifestyle management guideline includes recommendations for a dietary patterns that are heart healthy, including those with fruits, vegetables, and whole grains; limiting saturated fat, trans fat, and sodium intake; and for a physical activity level that complements dietary recommendations," said Dr. Robert H. Eckel, cochair of the writing committee, and professor of medicine at the University of Colorado, Denver.

The physical activity recommendations are based largely on a 2008 Department of Health and Human Services report, which provided support for 30-40 minutes of moderate to vigorous activity at least 3-4 days a week. For people who could benefit from a lower blood pressure, the guideline recommends a sodium intake of no more than 2,400 mg per day (a reduction from the current average of about 3,600 mg a day among U.S. adults), but points out that sodium intake of 1,500 mg a day or less has been associated with greater reductions in blood pressure.

Management of overweight and obesity in adults

The guidelines on the management of overweight and obesity in adults, developed with the Obesity Society, provide recommendations in five major areas and include a treatment algorithm on weight management, to help primary care providers address weight management in their patients, said Dr. Donna Ryan, cochair of the writing committee and professor emeritus at Louisiana State University’s Pennington Biomedical Research Center, Baton Rouge.

The guidelines help primary care providers identify which patients need to lose weight and how much weight loss is needed, as well as the benefits of weight loss, the best diet, the effectiveness of lifestyle interventions, and the benefits and risks of bariatric surgery.

The recommendations include the use of body mass index as "a quick and easy first screening step" to identify patients who may be at risk for obesity-related health problems, and weight circumference as an indicator of ASCVD risk, type 2 diabetes, and all-cause mortality, Dr. Ryan said.

Since the ideal weight loss diet has not been identified, providers should recommend a diet that results in reduced caloric intake, and the type of diet "should really be determined by the patient’s preferences and their health status," such as a reduced calorie, reduced sodium diet for an overweight, hypertensive patient. Another recommendation is a comprehensive approach to weight loss that involves diet and physical activity, with counseling for 6 months or more – which ideally should be on-site group or individual counseling sessions with a trained professional for at least 1 year.

Bariatric surgery may be an option for patients with a BMI of 35 kg/m², with comorbidities, or a BMI of 40. Although a "critical" area, recommendations on pharmacotherapy are not included, because at the time the guidelines were being developed, sibutramine (which has since been taken off the market) and orlistat were the only medications approved for weight loss in the United States.

Dr. Stone, Dr. Lloyd-Jones, and Dr. Rumsfeld had no disclosures.

Dr. Eckel disclosed ties to Merck, Pfizer, Abbott, Amylin, Eli Lilly, Esperion, Foodminds, Johnson & Johnson, Novo Nordisk, Vivus, GlaxoSmithKline, and Sanofi-Aventis/Regeneron.

Dr. Ryan disclosed ties to Alere Wellbeing, Amylin, Arena Pharmaceuticals, Eisai, Novo Nordisk, Nutrisystem, Orexigen, Takeda, and Vivus. She is chief medical officer of Scientific Intake.

[email protected]

The Food and Drug Administration has made a move toward further reducing – or eventually removing – the trans fat content in processed foods, with the "preliminary determination" that partially hydrogenated oils, the major source of trans fats, are "not generally recognized as safe" for use in food.

This determination is based on scientific evidence and expert scientific panel conclusions regarding the public health risks of trans fats, "and is an important step for removing harmful trans fat from processed foods," Dr. Margaret Hamburg, the FDA commissioner, said during a telephone briefing on Nov. 7 to announce the FDA’s action. This "will also allow adequate time for food manufacturers to reformulate products using alternative ingredients," she added.

She referred to the 2005 Institute of Medicine report concluding that trans fat, also called trans fatty acids, has no known health benefits, with no known safe level of consumption.

If this determination is finalized, partially hydrogenated oils will be considered food additives, and food manufacturers will not be able to add the ingredient to food unless authorized by regulation, according to the FDA statement.

To continue using trans fats as an ingredient, manufacturers would have to meet the safety standard for food additives, scientifically demonstrating that "there is a reasonable certainty of no harm from the use of the ingredients," said Michael Taylor, the FDA’s deputy commissioner for foods and veterinary medicine, during the briefing.

The FDA has opened a 60-day comment period for stakeholders to respond, and is particularly interested in comments from manufacturers on how long it will take to remove this ingredient from their products.

Although many manufacturers have voluntarily reduced the amount of trans fat content in their products, trans fats are still present in many processed foods, including coffee creamers, frosting, frozen pizzas, margarine, and microwave popcorn products. The FDA’s last major effort to address the trans fat content of foods was in 2006, when manufacturers were required to list trans fats and partially hydrogenated oils in the Nutrition Facts label on food packaging. As a result, the average daily intake of trans fat dropped to about 1 g/day in 2012, from 4.6 g/day in 2003, according to the FDA.

If the determination is finalized, the length of time it will take for the trans fat to be removed from food products is unclear. During the briefing, FDA officials could not provide any estimates as to how long this process will take. For now, consumers should check the food labels to see if the product contains trans fats and avoid products that list partially hydrogenated oils as an ingredient, Dr. Hamburg said.

Consumption of trans fats increases the risk of coronary heart disease by raising LDL cholesterol levels.

In a statement issued by the American Heart Association, CEO Nancy Brown said the FDA’s action "is a tremendous step forward in the fight against heart disease." The AHA has "long advocated for eliminating trans fat from the nation’s food supply, and we commend the FDA for responding to the numerous concerns and evidence submitted over the years about the dangers of this industrially produced ingredient."

The AHA cited estimates from the Centers for Disease Control and Prevention that avoiding foods containing trans fats could prevent 10,000-20,000 myocardial infarctions and 3,000-7,000 deaths caused by coronary heart disease each year in the United States.

The Federal Register notice, with information on how to submit comments, is available here.

[email protected]

The Food and Drug Administration has made a move toward further reducing – or eventually removing – the trans fat content in processed foods, with the "preliminary determination" that partially hydrogenated oils, the major source of trans fats, are "not generally recognized as safe" for use in food.

This determination is based on scientific evidence and expert scientific panel conclusions regarding the public health risks of trans fats, "and is an important step for removing harmful trans fat from processed foods," Dr. Margaret Hamburg, the FDA commissioner, said during a telephone briefing on Nov. 7 to announce the FDA’s action. This "will also allow adequate time for food manufacturers to reformulate products using alternative ingredients," she added.

She referred to the 2005 Institute of Medicine report concluding that trans fat, also called trans fatty acids, has no known health benefits, with no known safe level of consumption.

If this determination is finalized, partially hydrogenated oils will be considered food additives, and food manufacturers will not be able to add the ingredient to food unless authorized by regulation, according to the FDA statement.

To continue using trans fats as an ingredient, manufacturers would have to meet the safety standard for food additives, scientifically demonstrating that "there is a reasonable certainty of no harm from the use of the ingredients," said Michael Taylor, the FDA’s deputy commissioner for foods and veterinary medicine, during the briefing.

The FDA has opened a 60-day comment period for stakeholders to respond, and is particularly interested in comments from manufacturers on how long it will take to remove this ingredient from their products.

Although many manufacturers have voluntarily reduced the amount of trans fat content in their products, trans fats are still present in many processed foods, including coffee creamers, frosting, frozen pizzas, margarine, and microwave popcorn products. The FDA’s last major effort to address the trans fat content of foods was in 2006, when manufacturers were required to list trans fats and partially hydrogenated oils in the Nutrition Facts label on food packaging. As a result, the average daily intake of trans fat dropped to about 1 g/day in 2012, from 4.6 g/day in 2003, according to the FDA.

If the determination is finalized, the length of time it will take for the trans fat to be removed from food products is unclear. During the briefing, FDA officials could not provide any estimates as to how long this process will take. For now, consumers should check the food labels to see if the product contains trans fats and avoid products that list partially hydrogenated oils as an ingredient, Dr. Hamburg said.

Consumption of trans fats increases the risk of coronary heart disease by raising LDL cholesterol levels.

In a statement issued by the American Heart Association, CEO Nancy Brown said the FDA’s action "is a tremendous step forward in the fight against heart disease." The AHA has "long advocated for eliminating trans fat from the nation’s food supply, and we commend the FDA for responding to the numerous concerns and evidence submitted over the years about the dangers of this industrially produced ingredient."

The AHA cited estimates from the Centers for Disease Control and Prevention that avoiding foods containing trans fats could prevent 10,000-20,000 myocardial infarctions and 3,000-7,000 deaths caused by coronary heart disease each year in the United States.

The Federal Register notice, with information on how to submit comments, is available here.

[email protected]

The Food and Drug Administration has made a move toward further reducing – or eventually removing – the trans fat content in processed foods, with the "preliminary determination" that partially hydrogenated oils, the major source of trans fats, are "not generally recognized as safe" for use in food.

This determination is based on scientific evidence and expert scientific panel conclusions regarding the public health risks of trans fats, "and is an important step for removing harmful trans fat from processed foods," Dr. Margaret Hamburg, the FDA commissioner, said during a telephone briefing on Nov. 7 to announce the FDA’s action. This "will also allow adequate time for food manufacturers to reformulate products using alternative ingredients," she added.

She referred to the 2005 Institute of Medicine report concluding that trans fat, also called trans fatty acids, has no known health benefits, with no known safe level of consumption.

If this determination is finalized, partially hydrogenated oils will be considered food additives, and food manufacturers will not be able to add the ingredient to food unless authorized by regulation, according to the FDA statement.

To continue using trans fats as an ingredient, manufacturers would have to meet the safety standard for food additives, scientifically demonstrating that "there is a reasonable certainty of no harm from the use of the ingredients," said Michael Taylor, the FDA’s deputy commissioner for foods and veterinary medicine, during the briefing.

The FDA has opened a 60-day comment period for stakeholders to respond, and is particularly interested in comments from manufacturers on how long it will take to remove this ingredient from their products.

Although many manufacturers have voluntarily reduced the amount of trans fat content in their products, trans fats are still present in many processed foods, including coffee creamers, frosting, frozen pizzas, margarine, and microwave popcorn products. The FDA’s last major effort to address the trans fat content of foods was in 2006, when manufacturers were required to list trans fats and partially hydrogenated oils in the Nutrition Facts label on food packaging. As a result, the average daily intake of trans fat dropped to about 1 g/day in 2012, from 4.6 g/day in 2003, according to the FDA.

If the determination is finalized, the length of time it will take for the trans fat to be removed from food products is unclear. During the briefing, FDA officials could not provide any estimates as to how long this process will take. For now, consumers should check the food labels to see if the product contains trans fats and avoid products that list partially hydrogenated oils as an ingredient, Dr. Hamburg said.

Consumption of trans fats increases the risk of coronary heart disease by raising LDL cholesterol levels.

In a statement issued by the American Heart Association, CEO Nancy Brown said the FDA’s action "is a tremendous step forward in the fight against heart disease." The AHA has "long advocated for eliminating trans fat from the nation’s food supply, and we commend the FDA for responding to the numerous concerns and evidence submitted over the years about the dangers of this industrially produced ingredient."

The AHA cited estimates from the Centers for Disease Control and Prevention that avoiding foods containing trans fats could prevent 10,000-20,000 myocardial infarctions and 3,000-7,000 deaths caused by coronary heart disease each year in the United States.

The Federal Register notice, with information on how to submit comments, is available here.

[email protected]

The Food and Drug Administration has made a move toward further reducing – or eventually removing – the trans fat content in processed foods, with the "preliminary determination" that partially hydrogenated oils, the major source of trans fats, are "not generally recognized as safe" for use in food.

This determination is based on scientific evidence and expert scientific panel conclusions regarding the public health risks of trans fats, "and is an important step for removing harmful trans fat from processed foods," Dr. Margaret Hamburg, the FDA commissioner, said during a telephone briefing on Nov. 7 to announce the FDA’s action. This "will also allow adequate time for food manufacturers to reformulate products using alternative ingredients," she added.

She referred to the 2005 Institute of Medicine report concluding that trans fat, also called trans fatty acids, has no known health benefits, with no known safe level of consumption.

If this determination is finalized, partially hydrogenated oils will be considered food additives, and food manufacturers will not be able to add the ingredient to food unless authorized by regulation, according to the FDA statement.

To continue using trans fats as an ingredient, manufacturers would have to meet the safety standard for food additives, scientifically demonstrating that "there is a reasonable certainty of no harm from the use of the ingredients," said Michael Taylor, the FDA’s deputy commissioner for foods and veterinary medicine, during the briefing.

The FDA has opened a 60-day comment period for stakeholders to respond, and is particularly interested in comments from manufacturers on how long it will take to remove this ingredient from their products.

Although many manufacturers have voluntarily reduced the amount of trans fat content in their products, trans fats are still present in many processed foods, including coffee creamers, frosting, frozen pizzas, margarine, and microwave popcorn products. The FDA’s last major effort to address the trans fat content of foods was in 2006, when manufacturers were required to list trans fats and partially hydrogenated oils in the Nutrition Facts label on food packaging. As a result, the average daily intake of trans fat dropped to about 1 g/day in 2012, from 4.6 g/day in 2003, according to the FDA.

If the determination is finalized, the length of time it will take for the trans fat to be removed from food products is unclear. During the briefing, FDA officials could not provide any estimates as to how long this process will take. For now, consumers should check the food labels to see if the product contains trans fats and avoid products that list partially hydrogenated oils as an ingredient, Dr. Hamburg said.

Consumption of trans fats increases the risk of coronary heart disease by raising LDL cholesterol levels.

In a statement issued by the American Heart Association, CEO Nancy Brown said the FDA’s action "is a tremendous step forward in the fight against heart disease." The AHA has "long advocated for eliminating trans fat from the nation’s food supply, and we commend the FDA for responding to the numerous concerns and evidence submitted over the years about the dangers of this industrially produced ingredient."

The AHA cited estimates from the Centers for Disease Control and Prevention that avoiding foods containing trans fats could prevent 10,000-20,000 myocardial infarctions and 3,000-7,000 deaths caused by coronary heart disease each year in the United States.

The Federal Register notice, with information on how to submit comments, is available here.

[email protected]

The Food and Drug Administration has made a move toward further reducing – or eventually removing – the trans fat content in processed foods, with the "preliminary determination" that partially hydrogenated oils, the major source of trans fats, are "not generally recognized as safe" for use in food.

This determination is based on scientific evidence and expert scientific panel conclusions regarding the public health risks of trans fats, "and is an important step for removing harmful trans fat from processed foods," Dr. Margaret Hamburg, the FDA commissioner, said during a telephone briefing on Nov. 7 to announce the FDA’s action. This "will also allow adequate time for food manufacturers to reformulate products using alternative ingredients," she added.

She referred to the 2005 Institute of Medicine report concluding that trans fat, also called trans fatty acids, has no known health benefits, with no known safe level of consumption.

If this determination is finalized, partially hydrogenated oils will be considered food additives, and food manufacturers will not be able to add the ingredient to food unless authorized by regulation, according to the FDA statement.

To continue using trans fats as an ingredient, manufacturers would have to meet the safety standard for food additives, scientifically demonstrating that "there is a reasonable certainty of no harm from the use of the ingredients," said Michael Taylor, the FDA’s deputy commissioner for foods and veterinary medicine, during the briefing.

The FDA has opened a 60-day comment period for stakeholders to respond, and is particularly interested in comments from manufacturers on how long it will take to remove this ingredient from their products.

Although many manufacturers have voluntarily reduced the amount of trans fat content in their products, trans fats are still present in many processed foods, including coffee creamers, frosting, frozen pizzas, margarine, and microwave popcorn products. The FDA’s last major effort to address the trans fat content of foods was in 2006, when manufacturers were required to list trans fats and partially hydrogenated oils in the Nutrition Facts label on food packaging. As a result, the average daily intake of trans fat dropped to about 1 g/day in 2012, from 4.6 g/day in 2003, according to the FDA.

If the determination is finalized, the length of time it will take for the trans fat to be removed from food products is unclear. During the briefing, FDA officials could not provide any estimates as to how long this process will take. For now, consumers should check the food labels to see if the product contains trans fats and avoid products that list partially hydrogenated oils as an ingredient, Dr. Hamburg said.

Consumption of trans fats increases the risk of coronary heart disease by raising LDL cholesterol levels.

In a statement issued by the American Heart Association, CEO Nancy Brown said the FDA’s action "is a tremendous step forward in the fight against heart disease." The AHA has "long advocated for eliminating trans fat from the nation’s food supply, and we commend the FDA for responding to the numerous concerns and evidence submitted over the years about the dangers of this industrially produced ingredient."

The AHA cited estimates from the Centers for Disease Control and Prevention that avoiding foods containing trans fats could prevent 10,000-20,000 myocardial infarctions and 3,000-7,000 deaths caused by coronary heart disease each year in the United States.

The Federal Register notice, with information on how to submit comments, is available here.

[email protected]

The Food and Drug Administration has made a move toward further reducing – or eventually removing – the trans fat content in processed foods, with the "preliminary determination" that partially hydrogenated oils, the major source of trans fats, are "not generally recognized as safe" for use in food.

This determination is based on scientific evidence and expert scientific panel conclusions regarding the public health risks of trans fats, "and is an important step for removing harmful trans fat from processed foods," Dr. Margaret Hamburg, the FDA commissioner, said during a telephone briefing on Nov. 7 to announce the FDA’s action. This "will also allow adequate time for food manufacturers to reformulate products using alternative ingredients," she added.

She referred to the 2005 Institute of Medicine report concluding that trans fat, also called trans fatty acids, has no known health benefits, with no known safe level of consumption.

If this determination is finalized, partially hydrogenated oils will be considered food additives, and food manufacturers will not be able to add the ingredient to food unless authorized by regulation, according to the FDA statement.

To continue using trans fats as an ingredient, manufacturers would have to meet the safety standard for food additives, scientifically demonstrating that "there is a reasonable certainty of no harm from the use of the ingredients," said Michael Taylor, the FDA’s deputy commissioner for foods and veterinary medicine, during the briefing.

The FDA has opened a 60-day comment period for stakeholders to respond, and is particularly interested in comments from manufacturers on how long it will take to remove this ingredient from their products.

Although many manufacturers have voluntarily reduced the amount of trans fat content in their products, trans fats are still present in many processed foods, including coffee creamers, frosting, frozen pizzas, margarine, and microwave popcorn products. The FDA’s last major effort to address the trans fat content of foods was in 2006, when manufacturers were required to list trans fats and partially hydrogenated oils in the Nutrition Facts label on food packaging. As a result, the average daily intake of trans fat dropped to about 1 g/day in 2012, from 4.6 g/day in 2003, according to the FDA.

If the determination is finalized, the length of time it will take for the trans fat to be removed from food products is unclear. During the briefing, FDA officials could not provide any estimates as to how long this process will take. For now, consumers should check the food labels to see if the product contains trans fats and avoid products that list partially hydrogenated oils as an ingredient, Dr. Hamburg said.

Consumption of trans fats increases the risk of coronary heart disease by raising LDL cholesterol levels.

In a statement issued by the American Heart Association, CEO Nancy Brown said the FDA’s action "is a tremendous step forward in the fight against heart disease." The AHA has "long advocated for eliminating trans fat from the nation’s food supply, and we commend the FDA for responding to the numerous concerns and evidence submitted over the years about the dangers of this industrially produced ingredient."

The AHA cited estimates from the Centers for Disease Control and Prevention that avoiding foods containing trans fats could prevent 10,000-20,000 myocardial infarctions and 3,000-7,000 deaths caused by coronary heart disease each year in the United States.

The Federal Register notice, with information on how to submit comments, is available here.

[email protected]

WASHINGTON – Almost 100% of the patients with hepatitis C infection achieved a sustained virologic response rate 12 weeks after completing treatment with a fixed-dose oral combination of sofosbuvir and ledipasvir, with or without ribavirin, for 8 or 12 weeks, in a phase II study that enrolled previously untreated and treated patients, Dr. Eric Lawitz said at the annual meeting of the American Association for the Study of Liver Diseases.

The 100 patients in the study included those with cirrhosis and those who had previously failed treatment with protease inhibitors, said Dr. Lawitz, vice president of scientific and research development at the Texas Liver Institute, San Antonio. Treatment was well tolerated, and "all the regimens produced a consistently high sustained viral response rate, irrespective of the patient being either treatment naive or a protease failure," he said.

"The addition of ribavirin had no impact on outcome and in [patients with] protease failures, the results were independent of the presence or absence of cirrhosis," he added.

Sofosbuvir is a nucleotide polymerase inhibitor with activity against hepatitis C virus genotypes 1-6 and a high barrier to resistance, dosed once daily. Ledipasvir is an NS5A inhibitor, effective against genotypes 1a and 1b. The fixed-dose combination of the two antivirals contains 400 mg of sofosbuvir and 90 mg of ledipasvir, dosed once a day, in a single pill, with no food effect, he said. Neither is approved by the Food and Drug Administration, but approval of sofosbuvir is expected in December.

The study enrolled 100 patients with hepatitis C infection, genotype 1, in two cohorts: 60 treatment-naive noncirrhotic patients were randomized to one of three regimens, 8 weeks of the fixed-dose combination, with or without ribavirin; or 12 weeks of the fixed-dose combination, without ribavirin. The second cohort was 40 patients who had failed treatment with one of the HCV protease inhibitors (telaprevir) and were treated with the fixed-dose combination for 12 weeks, with and without ribavirin. The primary efficacy endpoint was the sustained virologic response (undetectable virus) 12 weeks after completing treatment (SVR12). SVR24 results were also obtained.

The mean age of those enrolled was 50 years (the oldest was 73 years); about half were black or Hispanic. About 15% had IL288B CC, which he noted was relatively low. About half of the treatment-experienced patients had compensated cirrhosis.

All but one patient completed the trial (one patient withdrew consent). Overall, treatment resulted in rapid drops in HCV RNA, and an SVR12 rate of 97%, with no viral breakthroughs, Dr. Lawitz said. Of the 60 treatment-naive patients without cirrhosis, 58 achieved an SVR12. Among those who had failed protease inhibitor treatment, 39 of 40 achieved an SVR 12, this group included 21 of the 22 patients with cirrhosis (who were not treated with ribavirin).

The SVR24 rate was also 97%, and the concordance rate between the SVR12 and SVR24 results was 100%, Dr. Lawitz said.

Of the three patients who failed to achieve an SVR12, two failures were in the group of treatment-naive patients (one treated for 8 weeks without ribavirin; and another patient treated for 12 weeks without ribavirin, who was lost to follow-up) and the other treated for 12 weeks. There was one failure in the protease inhibitor–treated group, a patient who relapsed in the 12-week arm without ribavirin.

Treatment was well tolerated, with no severe adverse events attributed to treatment, and no discontinuations for adverse events in any of the arms. Adverse events and lab abnormalities were consistent with the safety profile of ribavirin, and 24% of patients in the ribavirin arms required a dose reduction because of anemia. Among patients on the ribavirin-free regimens, the only adverse event reported more than 5% was upper respiratory infections.

Phase III studies (ION-1, ION-2, and ION-3) are underway, and are evaluating 8, 12, and 24 weeks of treatment with the fixed-dose combination, with and without ribavirin, in treatment-naive and treatment-experienced individuals with HCV genotype 1.

The study was sponsored by Gilead Sciences, the manufacturer of both drugs, and the fixed-dose combination. Dr. Lawitz’s disclosures include having received grant or research support from Gilead and speaking and teaching for the company, as well as other manufacturers.

[email protected]

WASHINGTON – Almost 100% of the patients with hepatitis C infection achieved a sustained virologic response rate 12 weeks after completing treatment with a fixed-dose oral combination of sofosbuvir and ledipasvir, with or without ribavirin, for 8 or 12 weeks, in a phase II study that enrolled previously untreated and treated patients, Dr. Eric Lawitz said at the annual meeting of the American Association for the Study of Liver Diseases.

The 100 patients in the study included those with cirrhosis and those who had previously failed treatment with protease inhibitors, said Dr. Lawitz, vice president of scientific and research development at the Texas Liver Institute, San Antonio. Treatment was well tolerated, and "all the regimens produced a consistently high sustained viral response rate, irrespective of the patient being either treatment naive or a protease failure," he said.

"The addition of ribavirin had no impact on outcome and in [patients with] protease failures, the results were independent of the presence or absence of cirrhosis," he added.

Sofosbuvir is a nucleotide polymerase inhibitor with activity against hepatitis C virus genotypes 1-6 and a high barrier to resistance, dosed once daily. Ledipasvir is an NS5A inhibitor, effective against genotypes 1a and 1b. The fixed-dose combination of the two antivirals contains 400 mg of sofosbuvir and 90 mg of ledipasvir, dosed once a day, in a single pill, with no food effect, he said. Neither is approved by the Food and Drug Administration, but approval of sofosbuvir is expected in December.

The study enrolled 100 patients with hepatitis C infection, genotype 1, in two cohorts: 60 treatment-naive noncirrhotic patients were randomized to one of three regimens, 8 weeks of the fixed-dose combination, with or without ribavirin; or 12 weeks of the fixed-dose combination, without ribavirin. The second cohort was 40 patients who had failed treatment with one of the HCV protease inhibitors (telaprevir) and were treated with the fixed-dose combination for 12 weeks, with and without ribavirin. The primary efficacy endpoint was the sustained virologic response (undetectable virus) 12 weeks after completing treatment (SVR12). SVR24 results were also obtained.

The mean age of those enrolled was 50 years (the oldest was 73 years); about half were black or Hispanic. About 15% had IL288B CC, which he noted was relatively low. About half of the treatment-experienced patients had compensated cirrhosis.

All but one patient completed the trial (one patient withdrew consent). Overall, treatment resulted in rapid drops in HCV RNA, and an SVR12 rate of 97%, with no viral breakthroughs, Dr. Lawitz said. Of the 60 treatment-naive patients without cirrhosis, 58 achieved an SVR12. Among those who had failed protease inhibitor treatment, 39 of 40 achieved an SVR 12, this group included 21 of the 22 patients with cirrhosis (who were not treated with ribavirin).

The SVR24 rate was also 97%, and the concordance rate between the SVR12 and SVR24 results was 100%, Dr. Lawitz said.

Of the three patients who failed to achieve an SVR12, two failures were in the group of treatment-naive patients (one treated for 8 weeks without ribavirin; and another patient treated for 12 weeks without ribavirin, who was lost to follow-up) and the other treated for 12 weeks. There was one failure in the protease inhibitor–treated group, a patient who relapsed in the 12-week arm without ribavirin.

Treatment was well tolerated, with no severe adverse events attributed to treatment, and no discontinuations for adverse events in any of the arms. Adverse events and lab abnormalities were consistent with the safety profile of ribavirin, and 24% of patients in the ribavirin arms required a dose reduction because of anemia. Among patients on the ribavirin-free regimens, the only adverse event reported more than 5% was upper respiratory infections.

Phase III studies (ION-1, ION-2, and ION-3) are underway, and are evaluating 8, 12, and 24 weeks of treatment with the fixed-dose combination, with and without ribavirin, in treatment-naive and treatment-experienced individuals with HCV genotype 1.

The study was sponsored by Gilead Sciences, the manufacturer of both drugs, and the fixed-dose combination. Dr. Lawitz’s disclosures include having received grant or research support from Gilead and speaking and teaching for the company, as well as other manufacturers.

[email protected]

WASHINGTON – Almost 100% of the patients with hepatitis C infection achieved a sustained virologic response rate 12 weeks after completing treatment with a fixed-dose oral combination of sofosbuvir and ledipasvir, with or without ribavirin, for 8 or 12 weeks, in a phase II study that enrolled previously untreated and treated patients, Dr. Eric Lawitz said at the annual meeting of the American Association for the Study of Liver Diseases.

The 100 patients in the study included those with cirrhosis and those who had previously failed treatment with protease inhibitors, said Dr. Lawitz, vice president of scientific and research development at the Texas Liver Institute, San Antonio. Treatment was well tolerated, and "all the regimens produced a consistently high sustained viral response rate, irrespective of the patient being either treatment naive or a protease failure," he said.

"The addition of ribavirin had no impact on outcome and in [patients with] protease failures, the results were independent of the presence or absence of cirrhosis," he added.

Sofosbuvir is a nucleotide polymerase inhibitor with activity against hepatitis C virus genotypes 1-6 and a high barrier to resistance, dosed once daily. Ledipasvir is an NS5A inhibitor, effective against genotypes 1a and 1b. The fixed-dose combination of the two antivirals contains 400 mg of sofosbuvir and 90 mg of ledipasvir, dosed once a day, in a single pill, with no food effect, he said. Neither is approved by the Food and Drug Administration, but approval of sofosbuvir is expected in December.

The study enrolled 100 patients with hepatitis C infection, genotype 1, in two cohorts: 60 treatment-naive noncirrhotic patients were randomized to one of three regimens, 8 weeks of the fixed-dose combination, with or without ribavirin; or 12 weeks of the fixed-dose combination, without ribavirin. The second cohort was 40 patients who had failed treatment with one of the HCV protease inhibitors (telaprevir) and were treated with the fixed-dose combination for 12 weeks, with and without ribavirin. The primary efficacy endpoint was the sustained virologic response (undetectable virus) 12 weeks after completing treatment (SVR12). SVR24 results were also obtained.

The mean age of those enrolled was 50 years (the oldest was 73 years); about half were black or Hispanic. About 15% had IL288B CC, which he noted was relatively low. About half of the treatment-experienced patients had compensated cirrhosis.

All but one patient completed the trial (one patient withdrew consent). Overall, treatment resulted in rapid drops in HCV RNA, and an SVR12 rate of 97%, with no viral breakthroughs, Dr. Lawitz said. Of the 60 treatment-naive patients without cirrhosis, 58 achieved an SVR12. Among those who had failed protease inhibitor treatment, 39 of 40 achieved an SVR 12, this group included 21 of the 22 patients with cirrhosis (who were not treated with ribavirin).

The SVR24 rate was also 97%, and the concordance rate between the SVR12 and SVR24 results was 100%, Dr. Lawitz said.

Of the three patients who failed to achieve an SVR12, two failures were in the group of treatment-naive patients (one treated for 8 weeks without ribavirin; and another patient treated for 12 weeks without ribavirin, who was lost to follow-up) and the other treated for 12 weeks. There was one failure in the protease inhibitor–treated group, a patient who relapsed in the 12-week arm without ribavirin.

Treatment was well tolerated, with no severe adverse events attributed to treatment, and no discontinuations for adverse events in any of the arms. Adverse events and lab abnormalities were consistent with the safety profile of ribavirin, and 24% of patients in the ribavirin arms required a dose reduction because of anemia. Among patients on the ribavirin-free regimens, the only adverse event reported more than 5% was upper respiratory infections.

Phase III studies (ION-1, ION-2, and ION-3) are underway, and are evaluating 8, 12, and 24 weeks of treatment with the fixed-dose combination, with and without ribavirin, in treatment-naive and treatment-experienced individuals with HCV genotype 1.

The study was sponsored by Gilead Sciences, the manufacturer of both drugs, and the fixed-dose combination. Dr. Lawitz’s disclosures include having received grant or research support from Gilead and speaking and teaching for the company, as well as other manufacturers.

[email protected]

The Food and Drug Administration has provided information on how health care professionals can ensure that patients who have benefitted from the leukemia drug ponatinib continue to have access to the treatment.

Less than a week after the agency announced that marketing and sales of the drug had been suspended because of the risk of life-threatening blood clots and severe narrowing of blood vessels associated with treatment, the FDA posted instructions on how to obtain emergency access to ponatinib through an Investigational New Drug (IND) application. This process entails contacting the FDA to obtain an emergency IND number for each patient who would benefit from continuing treatment and providing the manufacturer with that number to get ponatinib (Iclusig).

Health care professionals can obtain INDs for multiple patients during one phone call and should contact the agency at least 48-72 hours before the drug is needed, according to an FDA announcement.

The statement noted that health care professionals "may continue to use Iclusig for patients who they determine are responding to the drug and for whom the potential benefits outweigh the risks."

Ponatinib is a kinase inhibitor marketed by ARIAD Pharmaceuticals. It was approved in December 2012 for treating chronic myeloid leukemia and Philadelphia chromosome–positive acute lymphoblastic leukemia in adults.

Serious adverse events associated with ponatinib should be reported online to the FDA or by phone at 800-332-0178. Information about the IND program is available online. The FDA’s emergency IND telephone number is 301-796-7550 (between 8 a.m. and 4:30 p.m. EST, weekdays and 866-300-4374 after 4:30 p.m. EST. More information on how to obtain an IND for patients on ponatinib is available at http://www.fda.gov/Drugs/DrugSafety/ucm373040.htm.

[email protected]

The Food and Drug Administration has provided information on how health care professionals can ensure that patients who have benefitted from the leukemia drug ponatinib continue to have access to the treatment.

Less than a week after the agency announced that marketing and sales of the drug had been suspended because of the risk of life-threatening blood clots and severe narrowing of blood vessels associated with treatment, the FDA posted instructions on how to obtain emergency access to ponatinib through an Investigational New Drug (IND) application. This process entails contacting the FDA to obtain an emergency IND number for each patient who would benefit from continuing treatment and providing the manufacturer with that number to get ponatinib (Iclusig).

Health care professionals can obtain INDs for multiple patients during one phone call and should contact the agency at least 48-72 hours before the drug is needed, according to an FDA announcement.

The statement noted that health care professionals "may continue to use Iclusig for patients who they determine are responding to the drug and for whom the potential benefits outweigh the risks."

Ponatinib is a kinase inhibitor marketed by ARIAD Pharmaceuticals. It was approved in December 2012 for treating chronic myeloid leukemia and Philadelphia chromosome–positive acute lymphoblastic leukemia in adults.

Serious adverse events associated with ponatinib should be reported online to the FDA or by phone at 800-332-0178. Information about the IND program is available online. The FDA’s emergency IND telephone number is 301-796-7550 (between 8 a.m. and 4:30 p.m. EST, weekdays and 866-300-4374 after 4:30 p.m. EST. More information on how to obtain an IND for patients on ponatinib is available at http://www.fda.gov/Drugs/DrugSafety/ucm373040.htm.

[email protected]

The Food and Drug Administration has provided information on how health care professionals can ensure that patients who have benefitted from the leukemia drug ponatinib continue to have access to the treatment.

Less than a week after the agency announced that marketing and sales of the drug had been suspended because of the risk of life-threatening blood clots and severe narrowing of blood vessels associated with treatment, the FDA posted instructions on how to obtain emergency access to ponatinib through an Investigational New Drug (IND) application. This process entails contacting the FDA to obtain an emergency IND number for each patient who would benefit from continuing treatment and providing the manufacturer with that number to get ponatinib (Iclusig).

Health care professionals can obtain INDs for multiple patients during one phone call and should contact the agency at least 48-72 hours before the drug is needed, according to an FDA announcement.

The statement noted that health care professionals "may continue to use Iclusig for patients who they determine are responding to the drug and for whom the potential benefits outweigh the risks."

Ponatinib is a kinase inhibitor marketed by ARIAD Pharmaceuticals. It was approved in December 2012 for treating chronic myeloid leukemia and Philadelphia chromosome–positive acute lymphoblastic leukemia in adults.

Serious adverse events associated with ponatinib should be reported online to the FDA or by phone at 800-332-0178. Information about the IND program is available online. The FDA’s emergency IND telephone number is 301-796-7550 (between 8 a.m. and 4:30 p.m. EST, weekdays and 866-300-4374 after 4:30 p.m. EST. More information on how to obtain an IND for patients on ponatinib is available at http://www.fda.gov/Drugs/DrugSafety/ucm373040.htm.

[email protected]

WASHINGTON – Treatment with nonselective beta-blockers was not associated with an increased mortality risk in patients with decompensated cirrhosis, judging from findings from a retrospective longitudinal cohort study using Danish registry data presented by Dr. Ulrich Bang at the annual meeting of the American Association for the Study of Liver Diseases.

However, dose played a role in the mortality risk, with low-dose beta-blocker treatment (40 mg/day or less) reducing the risk of death "in all patients independent of severity of cirrhosis," said Dr. Bang of the department of gastroenterology, University Hospital of Hvidovre, Denmark. High-dose beta-blockers (more than 40 mg/day) were associated with increased mortality among patients with diuretic-resistant ascites as a feature of decompensated cirrhosis, he said. Using data on patients with alcoholic or biliary cirrhosis from the Danish national patient registry and medication use from the country’s national prescription registry, the study addressed the possibility that treatment with beta-blockers may have a negative impact on survival in severely ill cirrhotic patients. Although treatment with beta-blockers reduces the risk of mortality and repeat bleeding in patients with cirrhosis and varices, there has been concern about the possibility that beta-blockers have detrimental effects in patients with diuretic-refractory ascites because of a negative effect on cardiac output, he noted.

The primary outcome was mortality, adjusted for age, comorbidities, sex, and socioeconomic status.

Between 1995 and 2010, there were 1,576 people in the registry with mild decompensated cirrhosis (defined as those who had undergone one to four paracentesis procedures) and 239 people with severe decompensated cirrhosis (they had had more than four paracenteses). There were also 16,828 people with nonresistant "cirrhosis," who had not undergone a paracentesis procedure. Of the total of 18,643 patients, almost 90% had alcoholic cirrhosis, about 21% used a beta-blocker, and 64% used diuretics.

The median beta-blocker dose among the patients with mild cirrhosis was 30 mg/day (range 20-264 mg), and 24 mg/day (16-58 mg) among those with severe cirrhosis.

Among the patients with mild decompensated cirrhosis, mortality was 43% among those on a beta-blocker vs. 58% among those not on a beta-blocker, a significantly decreased risk of death. Among those on a beta-blocker, mortality was 38% among those on 40 mg or less per day vs. 51% among those on higher daily doses.

Mortality was also lower among those treated with a beta-blocker among the 239 patients with severe decompensated cirrhosis, Dr. Bang said. In this group, mortality was 47% among those not on a beta-blocker, compared with 41% of those on a beta-blocker. Of those on a beta-blocker, mortality was 36% among those on a dose of 40 mg or less a day but was 52% among those on more than 40 mg/day. The same patterns were seen in a subgroup of patients with diuretic-resistant decompensated cirrhosis.

The use of a beta-blocker was associated with a lower risk of spontaneous bacterial peritonitis in patients with decompensated cirrhosis, he said.

Dr. Bang had no disclosures.

[email protected]

WASHINGTON – Treatment with nonselective beta-blockers was not associated with an increased mortality risk in patients with decompensated cirrhosis, judging from findings from a retrospective longitudinal cohort study using Danish registry data presented by Dr. Ulrich Bang at the annual meeting of the American Association for the Study of Liver Diseases.

However, dose played a role in the mortality risk, with low-dose beta-blocker treatment (40 mg/day or less) reducing the risk of death "in all patients independent of severity of cirrhosis," said Dr. Bang of the department of gastroenterology, University Hospital of Hvidovre, Denmark. High-dose beta-blockers (more than 40 mg/day) were associated with increased mortality among patients with diuretic-resistant ascites as a feature of decompensated cirrhosis, he said. Using data on patients with alcoholic or biliary cirrhosis from the Danish national patient registry and medication use from the country’s national prescription registry, the study addressed the possibility that treatment with beta-blockers may have a negative impact on survival in severely ill cirrhotic patients. Although treatment with beta-blockers reduces the risk of mortality and repeat bleeding in patients with cirrhosis and varices, there has been concern about the possibility that beta-blockers have detrimental effects in patients with diuretic-refractory ascites because of a negative effect on cardiac output, he noted.

The primary outcome was mortality, adjusted for age, comorbidities, sex, and socioeconomic status.

Between 1995 and 2010, there were 1,576 people in the registry with mild decompensated cirrhosis (defined as those who had undergone one to four paracentesis procedures) and 239 people with severe decompensated cirrhosis (they had had more than four paracenteses). There were also 16,828 people with nonresistant "cirrhosis," who had not undergone a paracentesis procedure. Of the total of 18,643 patients, almost 90% had alcoholic cirrhosis, about 21% used a beta-blocker, and 64% used diuretics.

The median beta-blocker dose among the patients with mild cirrhosis was 30 mg/day (range 20-264 mg), and 24 mg/day (16-58 mg) among those with severe cirrhosis.

Among the patients with mild decompensated cirrhosis, mortality was 43% among those on a beta-blocker vs. 58% among those not on a beta-blocker, a significantly decreased risk of death. Among those on a beta-blocker, mortality was 38% among those on 40 mg or less per day vs. 51% among those on higher daily doses.

Mortality was also lower among those treated with a beta-blocker among the 239 patients with severe decompensated cirrhosis, Dr. Bang said. In this group, mortality was 47% among those not on a beta-blocker, compared with 41% of those on a beta-blocker. Of those on a beta-blocker, mortality was 36% among those on a dose of 40 mg or less a day but was 52% among those on more than 40 mg/day. The same patterns were seen in a subgroup of patients with diuretic-resistant decompensated cirrhosis.

The use of a beta-blocker was associated with a lower risk of spontaneous bacterial peritonitis in patients with decompensated cirrhosis, he said.

Dr. Bang had no disclosures.

[email protected]

WASHINGTON – Treatment with nonselective beta-blockers was not associated with an increased mortality risk in patients with decompensated cirrhosis, judging from findings from a retrospective longitudinal cohort study using Danish registry data presented by Dr. Ulrich Bang at the annual meeting of the American Association for the Study of Liver Diseases.

However, dose played a role in the mortality risk, with low-dose beta-blocker treatment (40 mg/day or less) reducing the risk of death "in all patients independent of severity of cirrhosis," said Dr. Bang of the department of gastroenterology, University Hospital of Hvidovre, Denmark. High-dose beta-blockers (more than 40 mg/day) were associated with increased mortality among patients with diuretic-resistant ascites as a feature of decompensated cirrhosis, he said. Using data on patients with alcoholic or biliary cirrhosis from the Danish national patient registry and medication use from the country’s national prescription registry, the study addressed the possibility that treatment with beta-blockers may have a negative impact on survival in severely ill cirrhotic patients. Although treatment with beta-blockers reduces the risk of mortality and repeat bleeding in patients with cirrhosis and varices, there has been concern about the possibility that beta-blockers have detrimental effects in patients with diuretic-refractory ascites because of a negative effect on cardiac output, he noted.

The primary outcome was mortality, adjusted for age, comorbidities, sex, and socioeconomic status.

Between 1995 and 2010, there were 1,576 people in the registry with mild decompensated cirrhosis (defined as those who had undergone one to four paracentesis procedures) and 239 people with severe decompensated cirrhosis (they had had more than four paracenteses). There were also 16,828 people with nonresistant "cirrhosis," who had not undergone a paracentesis procedure. Of the total of 18,643 patients, almost 90% had alcoholic cirrhosis, about 21% used a beta-blocker, and 64% used diuretics.

The median beta-blocker dose among the patients with mild cirrhosis was 30 mg/day (range 20-264 mg), and 24 mg/day (16-58 mg) among those with severe cirrhosis.

Among the patients with mild decompensated cirrhosis, mortality was 43% among those on a beta-blocker vs. 58% among those not on a beta-blocker, a significantly decreased risk of death. Among those on a beta-blocker, mortality was 38% among those on 40 mg or less per day vs. 51% among those on higher daily doses.

Mortality was also lower among those treated with a beta-blocker among the 239 patients with severe decompensated cirrhosis, Dr. Bang said. In this group, mortality was 47% among those not on a beta-blocker, compared with 41% of those on a beta-blocker. Of those on a beta-blocker, mortality was 36% among those on a dose of 40 mg or less a day but was 52% among those on more than 40 mg/day. The same patterns were seen in a subgroup of patients with diuretic-resistant decompensated cirrhosis.

The use of a beta-blocker was associated with a lower risk of spontaneous bacterial peritonitis in patients with decompensated cirrhosis, he said.

Dr. Bang had no disclosures.

[email protected]

WASHINGTON – Signals for several hematologic toxicities and for hepatic failure were identified in an analysis of serious adverse drug reactions associated with boceprevir treatment, according to an analysis of Food and Drug Administration data.

Signals for anemia, thrombocytopenia, and neutropenia – adverse events that were also reported in clinical trials of boceprevir before approval – were statistically significant, while the signal for hepatic failure approached significance, Bryan Love, Pharm.D., reported at the annual meeting of the American Association for the Study of Liver Diseases.

Reports of hepatic failure were unexpected, and should be investigated to provide insight into a possible causal association, he said.

Boceprevir (Victrelis) is one of two hepatitis C virus (HCV) protease inhibitors that were approved for treating chronic hepatitis C (genotype 1) in 2011, in combination with peginterferon and ribavirin, for both treatment-naive and treatment-experienced patients. Boceprevir, and the second drug, telaprevir, ushered in a new era for HCV treatments, with improved sustained virologic response rates, but their trade-offs included additional side effects, drug-drug interactions, as well as increased cost, he pointed out.

Dr. Love of the South Carolina College of Pharmacy, Columbia, and his coinvestigators searched for boceprevir-associated serious adverse drug reactions in the FDA Adverse Event Reporting System (FAERS) database between May 13, 2011 (the day of U.S. approval), and June 30, 2012, looking for those of special interest: thromboembolic events, severe cutaneous reactions, hematologic toxicities, and hepatic failure.

After duplicate reports were excluded, they identified 334 events in about 300 patients. The most frequent were neutropenia (168 reports), thrombocytopenia (80), and anemia (46). They also identified 13 severe cutaneous reactions, including one case of Stevens-Johnson syndrome.

There were 11 cases of hepatic failure in patients treated for a median of 111 days. Most (nine cases) were in women and most were outside of the United States; three reports specified that the patients had cirrhosis. Of the 11 patients, 7 died (6 women and 1 man).

On analysis, the investigators determined that the highest risk was for anemia, followed by neutropenia and thrombocytopenia, all statistically significant. The finding for hepatic failure approached statistical significance.

There were no new signals identified for other serious adverse events, including Stevens-Johnson syndrome, which he called "comforting."

Further investigation into the hepatic failure signal could include evaluation of patients in real world treatment settings, Dr. Love suggested. He pointed out that the adverse events are significantly underreported to the FDA and that the quality of those reports is unknown, making it difficult to determine causality.

Dr. Love reported no relevant financial conflicts of interest. The study was not funded.

[email protected]

WASHINGTON – Signals for several hematologic toxicities and for hepatic failure were identified in an analysis of serious adverse drug reactions associated with boceprevir treatment, according to an analysis of Food and Drug Administration data.

Signals for anemia, thrombocytopenia, and neutropenia – adverse events that were also reported in clinical trials of boceprevir before approval – were statistically significant, while the signal for hepatic failure approached significance, Bryan Love, Pharm.D., reported at the annual meeting of the American Association for the Study of Liver Diseases.

Reports of hepatic failure were unexpected, and should be investigated to provide insight into a possible causal association, he said.

Boceprevir (Victrelis) is one of two hepatitis C virus (HCV) protease inhibitors that were approved for treating chronic hepatitis C (genotype 1) in 2011, in combination with peginterferon and ribavirin, for both treatment-naive and treatment-experienced patients. Boceprevir, and the second drug, telaprevir, ushered in a new era for HCV treatments, with improved sustained virologic response rates, but their trade-offs included additional side effects, drug-drug interactions, as well as increased cost, he pointed out.

Dr. Love of the South Carolina College of Pharmacy, Columbia, and his coinvestigators searched for boceprevir-associated serious adverse drug reactions in the FDA Adverse Event Reporting System (FAERS) database between May 13, 2011 (the day of U.S. approval), and June 30, 2012, looking for those of special interest: thromboembolic events, severe cutaneous reactions, hematologic toxicities, and hepatic failure.

After duplicate reports were excluded, they identified 334 events in about 300 patients. The most frequent were neutropenia (168 reports), thrombocytopenia (80), and anemia (46). They also identified 13 severe cutaneous reactions, including one case of Stevens-Johnson syndrome.

There were 11 cases of hepatic failure in patients treated for a median of 111 days. Most (nine cases) were in women and most were outside of the United States; three reports specified that the patients had cirrhosis. Of the 11 patients, 7 died (6 women and 1 man).

On analysis, the investigators determined that the highest risk was for anemia, followed by neutropenia and thrombocytopenia, all statistically significant. The finding for hepatic failure approached statistical significance.

There were no new signals identified for other serious adverse events, including Stevens-Johnson syndrome, which he called "comforting."

Further investigation into the hepatic failure signal could include evaluation of patients in real world treatment settings, Dr. Love suggested. He pointed out that the adverse events are significantly underreported to the FDA and that the quality of those reports is unknown, making it difficult to determine causality.

Dr. Love reported no relevant financial conflicts of interest. The study was not funded.

[email protected]

WASHINGTON – Signals for several hematologic toxicities and for hepatic failure were identified in an analysis of serious adverse drug reactions associated with boceprevir treatment, according to an analysis of Food and Drug Administration data.

Signals for anemia, thrombocytopenia, and neutropenia – adverse events that were also reported in clinical trials of boceprevir before approval – were statistically significant, while the signal for hepatic failure approached significance, Bryan Love, Pharm.D., reported at the annual meeting of the American Association for the Study of Liver Diseases.

Reports of hepatic failure were unexpected, and should be investigated to provide insight into a possible causal association, he said.

Boceprevir (Victrelis) is one of two hepatitis C virus (HCV) protease inhibitors that were approved for treating chronic hepatitis C (genotype 1) in 2011, in combination with peginterferon and ribavirin, for both treatment-naive and treatment-experienced patients. Boceprevir, and the second drug, telaprevir, ushered in a new era for HCV treatments, with improved sustained virologic response rates, but their trade-offs included additional side effects, drug-drug interactions, as well as increased cost, he pointed out.

Dr. Love of the South Carolina College of Pharmacy, Columbia, and his coinvestigators searched for boceprevir-associated serious adverse drug reactions in the FDA Adverse Event Reporting System (FAERS) database between May 13, 2011 (the day of U.S. approval), and June 30, 2012, looking for those of special interest: thromboembolic events, severe cutaneous reactions, hematologic toxicities, and hepatic failure.

After duplicate reports were excluded, they identified 334 events in about 300 patients. The most frequent were neutropenia (168 reports), thrombocytopenia (80), and anemia (46). They also identified 13 severe cutaneous reactions, including one case of Stevens-Johnson syndrome.

There were 11 cases of hepatic failure in patients treated for a median of 111 days. Most (nine cases) were in women and most were outside of the United States; three reports specified that the patients had cirrhosis. Of the 11 patients, 7 died (6 women and 1 man).

On analysis, the investigators determined that the highest risk was for anemia, followed by neutropenia and thrombocytopenia, all statistically significant. The finding for hepatic failure approached statistical significance.

There were no new signals identified for other serious adverse events, including Stevens-Johnson syndrome, which he called "comforting."

Further investigation into the hepatic failure signal could include evaluation of patients in real world treatment settings, Dr. Love suggested. He pointed out that the adverse events are significantly underreported to the FDA and that the quality of those reports is unknown, making it difficult to determine causality.

Dr. Love reported no relevant financial conflicts of interest. The study was not funded.

[email protected]

WASHINGTON – Treatment with the hepatitis C antiviral drug sofosbuvir plus ribavirin resulted in high response rates in a study of 182 treatment-naive patients co-infected with hepatitis C and HIV, who were being treated with a variety of antiretroviral regimens, Dr. Mark Sulkowski said at the annual meeting of the American Association for the Study of Liver Disease.

The sustained virologic response rates 12 weeks after treatment (SVR12), the primary endpoint, were similar to the SVR12 rates in studies of patients infected with hepatitis C virus (HCV) only, who were treated with an interferon-free regimen of sofosbuvir plus ribavirin for 12-24 weeks, said Dr. Sulkowski, medical director of the viral hepatitis center in the divisions of infectious diseases and gastroenterology/hepatology at Johns Hopkins University, Baltimore.

"More importantly, sofosbuvir-ribavirin was effectively coadministered with multiple antiretroviral regimens, and there was no evidence of an adverse effect on the HIV disease," he said. The antiretroviral therapy (ART) regimens included HIV-1 protease inhibitors, reverse transcriptase (non-nucleoside and nucleoside) inhibitors, and integrase inhibitors.

The population of patients coinfected with HIV and HCV "has a high medical need" for an effective, interferon-free oral regimen that can be safely administered with ART, and drug interaction studies have shown that sofosbuvir can be administered with many antiretroviral drugs, Dr. Sulkowski said.

Sofosbuvir is an orally administered HCV-specific nucleotide polymerase inhibitor, with potent antiviral activity against HCV genotypes 1 through 6; it is taken once a day at a dose of 400 mg. A Food and Drug Administration advisory panel recently recommended that it be approved for treatment-naive adults with genotype 1 and 4 infections (in combination with pegylated interferon and ribavirin) and for treatment of adults with genotype 2 and 3 infections (in combination with ribavirin); approval is expected in December.

The study evaluated treatment with sofosbuvir,with 1,000-1,200 mg ribavirin a day, in HIV-positive patients coinfected with HCV: 114 patients with HCV genotype 1 infections treated for 24 weeks and 68 patients with genotypes 2 or 3 treated for 12 weeks. The study had broad inclusion criteria, and included patients with cirrhosis, with no platelet level cut off, treated with a wide range of antiretroviral therapy regimens (85%-98% were on ART). Their mean age was 48-49 years, 81%-82% were male, and most were white.

The SVR12 rates were 76% among patients with HCV genotype 1, 88% among genotype 2 patients, and 67% among genotype 3 patients, which were similar to the rates observed for patients infected with hepatitis C only, Dr. Sulkowski said. The two patients with HCV viral breakthrough were documented to be noncompliant with treatment, and there was no evidence of sofosbuvir resistance in the cases of virologic failures. In other studies of patients with HCV infection only, who were treated with sofosbuvir plus ribavirin without interferon, SVR12 rates have ranged from 68% among genotype 1 patients treated for 24 weeks to 97% among genotype 2 patients and 56% among genotype 3 patients treated for 12 weeks, Dr. Sulkowski said.

Overall, treatment was well tolerated, with a low rate of discontinuations from adverse events. Fatigue, headache, and insomnia were the most common adverse effects, and were similar in frequency and severity to that observed in studies of patients with HCV infection only. The rate of serious adverse events was 7%. There was one death, a suicide, in a patient treated for 12 weeks, who had a history of mental illness. There was no evidence of sofosbuvir resistance in the virologic failures.

About 21% of the patients treated for 24 weeks developed anemia, a known adverse effect of ribavirin, and 25% of those patients required a reduction in ribavirin dose.

As for HIV safety, there was no evidence of HIV breakthrough, Dr. Sulkowski said. Two patients with transient HIV viral breakthrough were not adhering to ART. There was no drop in the CD4 T-cell percentage values; there was a drop in absolute CD4 T cells, which he said is consistent with a known ribavirin-mediated decrease in lymphocytes.

Dr. Sulkowski disclosed that the study was funded by Gilead Sciences, the manufacturer of sofosbuvir.

[email protected]

WASHINGTON – Treatment with the hepatitis C antiviral drug sofosbuvir plus ribavirin resulted in high response rates in a study of 182 treatment-naive patients co-infected with hepatitis C and HIV, who were being treated with a variety of antiretroviral regimens, Dr. Mark Sulkowski said at the annual meeting of the American Association for the Study of Liver Disease.

The sustained virologic response rates 12 weeks after treatment (SVR12), the primary endpoint, were similar to the SVR12 rates in studies of patients infected with hepatitis C virus (HCV) only, who were treated with an interferon-free regimen of sofosbuvir plus ribavirin for 12-24 weeks, said Dr. Sulkowski, medical director of the viral hepatitis center in the divisions of infectious diseases and gastroenterology/hepatology at Johns Hopkins University, Baltimore.

"More importantly, sofosbuvir-ribavirin was effectively coadministered with multiple antiretroviral regimens, and there was no evidence of an adverse effect on the HIV disease," he said. The antiretroviral therapy (ART) regimens included HIV-1 protease inhibitors, reverse transcriptase (non-nucleoside and nucleoside) inhibitors, and integrase inhibitors.

The population of patients coinfected with HIV and HCV "has a high medical need" for an effective, interferon-free oral regimen that can be safely administered with ART, and drug interaction studies have shown that sofosbuvir can be administered with many antiretroviral drugs, Dr. Sulkowski said.

Sofosbuvir is an orally administered HCV-specific nucleotide polymerase inhibitor, with potent antiviral activity against HCV genotypes 1 through 6; it is taken once a day at a dose of 400 mg. A Food and Drug Administration advisory panel recently recommended that it be approved for treatment-naive adults with genotype 1 and 4 infections (in combination with pegylated interferon and ribavirin) and for treatment of adults with genotype 2 and 3 infections (in combination with ribavirin); approval is expected in December.

The study evaluated treatment with sofosbuvir,with 1,000-1,200 mg ribavirin a day, in HIV-positive patients coinfected with HCV: 114 patients with HCV genotype 1 infections treated for 24 weeks and 68 patients with genotypes 2 or 3 treated for 12 weeks. The study had broad inclusion criteria, and included patients with cirrhosis, with no platelet level cut off, treated with a wide range of antiretroviral therapy regimens (85%-98% were on ART). Their mean age was 48-49 years, 81%-82% were male, and most were white.

The SVR12 rates were 76% among patients with HCV genotype 1, 88% among genotype 2 patients, and 67% among genotype 3 patients, which were similar to the rates observed for patients infected with hepatitis C only, Dr. Sulkowski said. The two patients with HCV viral breakthrough were documented to be noncompliant with treatment, and there was no evidence of sofosbuvir resistance in the cases of virologic failures. In other studies of patients with HCV infection only, who were treated with sofosbuvir plus ribavirin without interferon, SVR12 rates have ranged from 68% among genotype 1 patients treated for 24 weeks to 97% among genotype 2 patients and 56% among genotype 3 patients treated for 12 weeks, Dr. Sulkowski said.

Overall, treatment was well tolerated, with a low rate of discontinuations from adverse events. Fatigue, headache, and insomnia were the most common adverse effects, and were similar in frequency and severity to that observed in studies of patients with HCV infection only. The rate of serious adverse events was 7%. There was one death, a suicide, in a patient treated for 12 weeks, who had a history of mental illness. There was no evidence of sofosbuvir resistance in the virologic failures.

About 21% of the patients treated for 24 weeks developed anemia, a known adverse effect of ribavirin, and 25% of those patients required a reduction in ribavirin dose.

As for HIV safety, there was no evidence of HIV breakthrough, Dr. Sulkowski said. Two patients with transient HIV viral breakthrough were not adhering to ART. There was no drop in the CD4 T-cell percentage values; there was a drop in absolute CD4 T cells, which he said is consistent with a known ribavirin-mediated decrease in lymphocytes.

Dr. Sulkowski disclosed that the study was funded by Gilead Sciences, the manufacturer of sofosbuvir.

[email protected]

WASHINGTON – Treatment with the hepatitis C antiviral drug sofosbuvir plus ribavirin resulted in high response rates in a study of 182 treatment-naive patients co-infected with hepatitis C and HIV, who were being treated with a variety of antiretroviral regimens, Dr. Mark Sulkowski said at the annual meeting of the American Association for the Study of Liver Disease.

The sustained virologic response rates 12 weeks after treatment (SVR12), the primary endpoint, were similar to the SVR12 rates in studies of patients infected with hepatitis C virus (HCV) only, who were treated with an interferon-free regimen of sofosbuvir plus ribavirin for 12-24 weeks, said Dr. Sulkowski, medical director of the viral hepatitis center in the divisions of infectious diseases and gastroenterology/hepatology at Johns Hopkins University, Baltimore.

"More importantly, sofosbuvir-ribavirin was effectively coadministered with multiple antiretroviral regimens, and there was no evidence of an adverse effect on the HIV disease," he said. The antiretroviral therapy (ART) regimens included HIV-1 protease inhibitors, reverse transcriptase (non-nucleoside and nucleoside) inhibitors, and integrase inhibitors.

The population of patients coinfected with HIV and HCV "has a high medical need" for an effective, interferon-free oral regimen that can be safely administered with ART, and drug interaction studies have shown that sofosbuvir can be administered with many antiretroviral drugs, Dr. Sulkowski said.

Sofosbuvir is an orally administered HCV-specific nucleotide polymerase inhibitor, with potent antiviral activity against HCV genotypes 1 through 6; it is taken once a day at a dose of 400 mg. A Food and Drug Administration advisory panel recently recommended that it be approved for treatment-naive adults with genotype 1 and 4 infections (in combination with pegylated interferon and ribavirin) and for treatment of adults with genotype 2 and 3 infections (in combination with ribavirin); approval is expected in December.

The study evaluated treatment with sofosbuvir,with 1,000-1,200 mg ribavirin a day, in HIV-positive patients coinfected with HCV: 114 patients with HCV genotype 1 infections treated for 24 weeks and 68 patients with genotypes 2 or 3 treated for 12 weeks. The study had broad inclusion criteria, and included patients with cirrhosis, with no platelet level cut off, treated with a wide range of antiretroviral therapy regimens (85%-98% were on ART). Their mean age was 48-49 years, 81%-82% were male, and most were white.

The SVR12 rates were 76% among patients with HCV genotype 1, 88% among genotype 2 patients, and 67% among genotype 3 patients, which were similar to the rates observed for patients infected with hepatitis C only, Dr. Sulkowski said. The two patients with HCV viral breakthrough were documented to be noncompliant with treatment, and there was no evidence of sofosbuvir resistance in the cases of virologic failures. In other studies of patients with HCV infection only, who were treated with sofosbuvir plus ribavirin without interferon, SVR12 rates have ranged from 68% among genotype 1 patients treated for 24 weeks to 97% among genotype 2 patients and 56% among genotype 3 patients treated for 12 weeks, Dr. Sulkowski said.

Overall, treatment was well tolerated, with a low rate of discontinuations from adverse events. Fatigue, headache, and insomnia were the most common adverse effects, and were similar in frequency and severity to that observed in studies of patients with HCV infection only. The rate of serious adverse events was 7%. There was one death, a suicide, in a patient treated for 12 weeks, who had a history of mental illness. There was no evidence of sofosbuvir resistance in the virologic failures.

About 21% of the patients treated for 24 weeks developed anemia, a known adverse effect of ribavirin, and 25% of those patients required a reduction in ribavirin dose.

As for HIV safety, there was no evidence of HIV breakthrough, Dr. Sulkowski said. Two patients with transient HIV viral breakthrough were not adhering to ART. There was no drop in the CD4 T-cell percentage values; there was a drop in absolute CD4 T cells, which he said is consistent with a known ribavirin-mediated decrease in lymphocytes.

Dr. Sulkowski disclosed that the study was funded by Gilead Sciences, the manufacturer of sofosbuvir.

[email protected]

WASHINGTON – Treatment with the hepatitis C antiviral drug sofosbuvir plus ribavirin resulted in high response rates in a study of 182 treatment-naive patients co-infected with hepatitis C and HIV, who were being treated with a variety of antiretroviral regimens, Dr. Mark Sulkowski said at the annual meeting of the American Association for the Study of Liver Disease.

The sustained virologic response rates 12 weeks after treatment (SVR12), the primary endpoint, were similar to the SVR12 rates in studies of patients infected with hepatitis C virus (HCV) only, who were treated with an interferon-free regimen of sofosbuvir plus ribavirin for 12-24 weeks, said Dr. Sulkowski, medical director of the viral hepatitis center in the divisions of infectious diseases and gastroenterology/hepatology at Johns Hopkins University, Baltimore.

"More importantly, sofosbuvir-ribavirin was effectively coadministered with multiple antiretroviral regimens, and there was no evidence of an adverse effect on the HIV disease," he said. The antiretroviral therapy (ART) regimens included HIV-1 protease inhibitors, reverse transcriptase (non-nucleoside and nucleoside) inhibitors, and integrase inhibitors.

The population of patients coinfected with HIV and HCV "has a high medical need" for an effective, interferon-free oral regimen that can be safely administered with ART, and drug interaction studies have shown that sofosbuvir can be administered with many antiretroviral drugs, Dr. Sulkowski said.

Sofosbuvir is an orally administered HCV-specific nucleotide polymerase inhibitor, with potent antiviral activity against HCV genotypes 1 through 6; it is taken once a day at a dose of 400 mg. A Food and Drug Administration advisory panel recently recommended that it be approved for treatment-naive adults with genotype 1 and 4 infections (in combination with pegylated interferon and ribavirin) and for treatment of adults with genotype 2 and 3 infections (in combination with ribavirin); approval is expected in December.

The study evaluated treatment with sofosbuvir,with 1,000-1,200 mg ribavirin a day, in HIV-positive patients coinfected with HCV: 114 patients with HCV genotype 1 infections treated for 24 weeks and 68 patients with genotypes 2 or 3 treated for 12 weeks. The study had broad inclusion criteria, and included patients with cirrhosis, with no platelet level cut off, treated with a wide range of antiretroviral therapy regimens (85%-98% were on ART). Their mean age was 48-49 years, 81%-82% were male, and most were white.

The SVR12 rates were 76% among patients with HCV genotype 1, 88% among genotype 2 patients, and 67% among genotype 3 patients, which were similar to the rates observed for patients infected with hepatitis C only, Dr. Sulkowski said. The two patients with HCV viral breakthrough were documented to be noncompliant with treatment, and there was no evidence of sofosbuvir resistance in the cases of virologic failures. In other studies of patients with HCV infection only, who were treated with sofosbuvir plus ribavirin without interferon, SVR12 rates have ranged from 68% among genotype 1 patients treated for 24 weeks to 97% among genotype 2 patients and 56% among genotype 3 patients treated for 12 weeks, Dr. Sulkowski said.

Overall, treatment was well tolerated, with a low rate of discontinuations from adverse events. Fatigue, headache, and insomnia were the most common adverse effects, and were similar in frequency and severity to that observed in studies of patients with HCV infection only. The rate of serious adverse events was 7%. There was one death, a suicide, in a patient treated for 12 weeks, who had a history of mental illness. There was no evidence of sofosbuvir resistance in the virologic failures.

About 21% of the patients treated for 24 weeks developed anemia, a known adverse effect of ribavirin, and 25% of those patients required a reduction in ribavirin dose.

As for HIV safety, there was no evidence of HIV breakthrough, Dr. Sulkowski said. Two patients with transient HIV viral breakthrough were not adhering to ART. There was no drop in the CD4 T-cell percentage values; there was a drop in absolute CD4 T cells, which he said is consistent with a known ribavirin-mediated decrease in lymphocytes.

Dr. Sulkowski disclosed that the study was funded by Gilead Sciences, the manufacturer of sofosbuvir.

[email protected]

WASHINGTON – Treatment with the hepatitis C antiviral drug sofosbuvir plus ribavirin resulted in high response rates in a study of 182 treatment-naive patients co-infected with hepatitis C and HIV, who were being treated with a variety of antiretroviral regimens, Dr. Mark Sulkowski said at the annual meeting of the American Association for the Study of Liver Disease.

The sustained virologic response rates 12 weeks after treatment (SVR12), the primary endpoint, were similar to the SVR12 rates in studies of patients infected with hepatitis C virus (HCV) only, who were treated with an interferon-free regimen of sofosbuvir plus ribavirin for 12-24 weeks, said Dr. Sulkowski, medical director of the viral hepatitis center in the divisions of infectious diseases and gastroenterology/hepatology at Johns Hopkins University, Baltimore.

"More importantly, sofosbuvir-ribavirin was effectively coadministered with multiple antiretroviral regimens, and there was no evidence of an adverse effect on the HIV disease," he said. The antiretroviral therapy (ART) regimens included HIV-1 protease inhibitors, reverse transcriptase (non-nucleoside and nucleoside) inhibitors, and integrase inhibitors.

The population of patients coinfected with HIV and HCV "has a high medical need" for an effective, interferon-free oral regimen that can be safely administered with ART, and drug interaction studies have shown that sofosbuvir can be administered with many antiretroviral drugs, Dr. Sulkowski said.

Sofosbuvir is an orally administered HCV-specific nucleotide polymerase inhibitor, with potent antiviral activity against HCV genotypes 1 through 6; it is taken once a day at a dose of 400 mg. A Food and Drug Administration advisory panel recently recommended that it be approved for treatment-naive adults with genotype 1 and 4 infections (in combination with pegylated interferon and ribavirin) and for treatment of adults with genotype 2 and 3 infections (in combination with ribavirin); approval is expected in December.

The study evaluated treatment with sofosbuvir,with 1,000-1,200 mg ribavirin a day, in HIV-positive patients coinfected with HCV: 114 patients with HCV genotype 1 infections treated for 24 weeks and 68 patients with genotypes 2 or 3 treated for 12 weeks. The study had broad inclusion criteria, and included patients with cirrhosis, with no platelet level cut off, treated with a wide range of antiretroviral therapy regimens (85%-98% were on ART). Their mean age was 48-49 years, 81%-82% were male, and most were white.

The SVR12 rates were 76% among patients with HCV genotype 1, 88% among genotype 2 patients, and 67% among genotype 3 patients, which were similar to the rates observed for patients infected with hepatitis C only, Dr. Sulkowski said. The two patients with HCV viral breakthrough were documented to be noncompliant with treatment, and there was no evidence of sofosbuvir resistance in the cases of virologic failures. In other studies of patients with HCV infection only, who were treated with sofosbuvir plus ribavirin without interferon, SVR12 rates have ranged from 68% among genotype 1 patients treated for 24 weeks to 97% among genotype 2 patients and 56% among genotype 3 patients treated for 12 weeks, Dr. Sulkowski said.

Overall, treatment was well tolerated, with a low rate of discontinuations from adverse events. Fatigue, headache, and insomnia were the most common adverse effects, and were similar in frequency and severity to that observed in studies of patients with HCV infection only. The rate of serious adverse events was 7%. There was one death, a suicide, in a patient treated for 12 weeks, who had a history of mental illness. There was no evidence of sofosbuvir resistance in the virologic failures.

About 21% of the patients treated for 24 weeks developed anemia, a known adverse effect of ribavirin, and 25% of those patients required a reduction in ribavirin dose.

As for HIV safety, there was no evidence of HIV breakthrough, Dr. Sulkowski said. Two patients with transient HIV viral breakthrough were not adhering to ART. There was no drop in the CD4 T-cell percentage values; there was a drop in absolute CD4 T cells, which he said is consistent with a known ribavirin-mediated decrease in lymphocytes.

Dr. Sulkowski disclosed that the study was funded by Gilead Sciences, the manufacturer of sofosbuvir.

[email protected]

WASHINGTON – Treatment with the hepatitis C antiviral drug sofosbuvir plus ribavirin resulted in high response rates in a study of 182 treatment-naive patients co-infected with hepatitis C and HIV, who were being treated with a variety of antiretroviral regimens, Dr. Mark Sulkowski said at the annual meeting of the American Association for the Study of Liver Disease.

The sustained virologic response rates 12 weeks after treatment (SVR12), the primary endpoint, were similar to the SVR12 rates in studies of patients infected with hepatitis C virus (HCV) only, who were treated with an interferon-free regimen of sofosbuvir plus ribavirin for 12-24 weeks, said Dr. Sulkowski, medical director of the viral hepatitis center in the divisions of infectious diseases and gastroenterology/hepatology at Johns Hopkins University, Baltimore.

"More importantly, sofosbuvir-ribavirin was effectively coadministered with multiple antiretroviral regimens, and there was no evidence of an adverse effect on the HIV disease," he said. The antiretroviral therapy (ART) regimens included HIV-1 protease inhibitors, reverse transcriptase (non-nucleoside and nucleoside) inhibitors, and integrase inhibitors.

The population of patients coinfected with HIV and HCV "has a high medical need" for an effective, interferon-free oral regimen that can be safely administered with ART, and drug interaction studies have shown that sofosbuvir can be administered with many antiretroviral drugs, Dr. Sulkowski said.

Sofosbuvir is an orally administered HCV-specific nucleotide polymerase inhibitor, with potent antiviral activity against HCV genotypes 1 through 6; it is taken once a day at a dose of 400 mg. A Food and Drug Administration advisory panel recently recommended that it be approved for treatment-naive adults with genotype 1 and 4 infections (in combination with pegylated interferon and ribavirin) and for treatment of adults with genotype 2 and 3 infections (in combination with ribavirin); approval is expected in December.

The study evaluated treatment with sofosbuvir,with 1,000-1,200 mg ribavirin a day, in HIV-positive patients coinfected with HCV: 114 patients with HCV genotype 1 infections treated for 24 weeks and 68 patients with genotypes 2 or 3 treated for 12 weeks. The study had broad inclusion criteria, and included patients with cirrhosis, with no platelet level cut off, treated with a wide range of antiretroviral therapy regimens (85%-98% were on ART). Their mean age was 48-49 years, 81%-82% were male, and most were white.

The SVR12 rates were 76% among patients with HCV genotype 1, 88% among genotype 2 patients, and 67% among genotype 3 patients, which were similar to the rates observed for patients infected with hepatitis C only, Dr. Sulkowski said. The two patients with HCV viral breakthrough were documented to be noncompliant with treatment, and there was no evidence of sofosbuvir resistance in the cases of virologic failures. In other studies of patients with HCV infection only, who were treated with sofosbuvir plus ribavirin without interferon, SVR12 rates have ranged from 68% among genotype 1 patients treated for 24 weeks to 97% among genotype 2 patients and 56% among genotype 3 patients treated for 12 weeks, Dr. Sulkowski said.

Overall, treatment was well tolerated, with a low rate of discontinuations from adverse events. Fatigue, headache, and insomnia were the most common adverse effects, and were similar in frequency and severity to that observed in studies of patients with HCV infection only. The rate of serious adverse events was 7%. There was one death, a suicide, in a patient treated for 12 weeks, who had a history of mental illness. There was no evidence of sofosbuvir resistance in the virologic failures.

About 21% of the patients treated for 24 weeks developed anemia, a known adverse effect of ribavirin, and 25% of those patients required a reduction in ribavirin dose.

As for HIV safety, there was no evidence of HIV breakthrough, Dr. Sulkowski said. Two patients with transient HIV viral breakthrough were not adhering to ART. There was no drop in the CD4 T-cell percentage values; there was a drop in absolute CD4 T cells, which he said is consistent with a known ribavirin-mediated decrease in lymphocytes.

Dr. Sulkowski disclosed that the study was funded by Gilead Sciences, the manufacturer of sofosbuvir.

[email protected]

WASHINGTON – Hepatoxicity from herbal and dietary supplements is on the rise in the United States, with body-building supplements being implicated as the most common cause of liver injury, according to the results of a recent study.

Between September 2004 and March 2013, 845 cases of liver injury were thought to be "definitely, highly likely, or probably" from an herbal or dietary supplement, or from prescription drugs. Of these cases, 136 (16%) were attributed to a product in the herbal and dietary supplement category. Patients reported consuming a total of 262 different herbal and dietary supplements; 30% were body-building products. Cases of liver injury from all herbal and dietary supplements increased from 7% in 2004-2005 to 20% in 2010-2012, reported Dr. Victor J. Navarro at the annual meeting of the American Association for the Study of Liver Diseases.

The prospective study used data from the Drug-Induced Liver Injury Network (DILIN). The network was established in 2003 by the National Institute of Diabetes and Digestive and Kidney Diseases to collect and analyze cases of severe liver injury caused by prescription and over-the-counter drugs, as well as alternative medications, including herbal products and supplements.

Of the hepatotoxicity cases due to supplements, 7 were excluded because they involved both body-building and other herbal and dietary supplements. Of the remaining 129 cases, 44 were attributed to body-building supplements and 85 cases were attributed to other types of herbal and dietary supplements. These cases were compared with 709 cases of drug-induced liver injury, noted Dr. Navarro, chair of the division of hepatology, Einstein Healthcare Network, Philadelphia.

Clinical features and demographic characteristics differed between the groups. The 44 patients with injury induced by body-building supplements were younger (mean age 33 years, vs. 48-50 years in the other two groups), and all were men. In the other two groups, 35%-37% of cases occurred in men.

As for clinical presentation, "the body-building supplement injury cases stood apart," as there was a "distinct presentation of prolonged jaundice," Dr. Navarro noted. "These patients tended to have fewer comorbid conditions," were heavier, and were "uniformly symptomatic." They all had jaundice, and 84% had pruritus. Of patients in the other herbal and dietary supplement group, 78% presented with jaundice and 48% presented with pruritus, compared with and 68% and 53%, respectively, of those with drug-induced liver injury.

Body-building liver injury cases required hospitalization more often, but no patients in this group died or had a liver transplant. There were deaths from all causes in the two other groups, but the differences were not significant. However, 13% of the cases of liver injury from other supplements resulted in a liver transplant, compared with 3% among the drug-induced liver injury group, a significant difference.

The higher transplant rate indicates that the hepatoxicity induced by non-body-building supplements "may be more severe" than injury induced by prescription drugs, Dr. Navarro observed.

Other marked differences between the groups included a serum total bilirubin that was significantly higher and persisted significantly longer in patients with liver injury from body-building supplements.

Although the study results indicate that hepatotoxicity due to herbal and dietary supplements is increasing, this was not a population-based study, and so "additional efforts to characterize the true burden of disease in the U.S. population are needed," and are being addressed by DILIN, Dr. Navarro said.

The National Institutes of Health sponsored the study. Dr. Navarro had no relevant disclosures. Information about DILIN is available here.

[email protected]

WASHINGTON – Hepatoxicity from herbal and dietary supplements is on the rise in the United States, with body-building supplements being implicated as the most common cause of liver injury, according to the results of a recent study.

Between September 2004 and March 2013, 845 cases of liver injury were thought to be "definitely, highly likely, or probably" from an herbal or dietary supplement, or from prescription drugs. Of these cases, 136 (16%) were attributed to a product in the herbal and dietary supplement category. Patients reported consuming a total of 262 different herbal and dietary supplements; 30% were body-building products. Cases of liver injury from all herbal and dietary supplements increased from 7% in 2004-2005 to 20% in 2010-2012, reported Dr. Victor J. Navarro at the annual meeting of the American Association for the Study of Liver Diseases.

The prospective study used data from the Drug-Induced Liver Injury Network (DILIN). The network was established in 2003 by the National Institute of Diabetes and Digestive and Kidney Diseases to collect and analyze cases of severe liver injury caused by prescription and over-the-counter drugs, as well as alternative medications, including herbal products and supplements.

Of the hepatotoxicity cases due to supplements, 7 were excluded because they involved both body-building and other herbal and dietary supplements. Of the remaining 129 cases, 44 were attributed to body-building supplements and 85 cases were attributed to other types of herbal and dietary supplements. These cases were compared with 709 cases of drug-induced liver injury, noted Dr. Navarro, chair of the division of hepatology, Einstein Healthcare Network, Philadelphia.

Clinical features and demographic characteristics differed between the groups. The 44 patients with injury induced by body-building supplements were younger (mean age 33 years, vs. 48-50 years in the other two groups), and all were men. In the other two groups, 35%-37% of cases occurred in men.

As for clinical presentation, "the body-building supplement injury cases stood apart," as there was a "distinct presentation of prolonged jaundice," Dr. Navarro noted. "These patients tended to have fewer comorbid conditions," were heavier, and were "uniformly symptomatic." They all had jaundice, and 84% had pruritus. Of patients in the other herbal and dietary supplement group, 78% presented with jaundice and 48% presented with pruritus, compared with and 68% and 53%, respectively, of those with drug-induced liver injury.

Body-building liver injury cases required hospitalization more often, but no patients in this group died or had a liver transplant. There were deaths from all causes in the two other groups, but the differences were not significant. However, 13% of the cases of liver injury from other supplements resulted in a liver transplant, compared with 3% among the drug-induced liver injury group, a significant difference.

The higher transplant rate indicates that the hepatoxicity induced by non-body-building supplements "may be more severe" than injury induced by prescription drugs, Dr. Navarro observed.

Other marked differences between the groups included a serum total bilirubin that was significantly higher and persisted significantly longer in patients with liver injury from body-building supplements.

Although the study results indicate that hepatotoxicity due to herbal and dietary supplements is increasing, this was not a population-based study, and so "additional efforts to characterize the true burden of disease in the U.S. population are needed," and are being addressed by DILIN, Dr. Navarro said.

The National Institutes of Health sponsored the study. Dr. Navarro had no relevant disclosures. Information about DILIN is available here.

[email protected]

WASHINGTON – Hepatoxicity from herbal and dietary supplements is on the rise in the United States, with body-building supplements being implicated as the most common cause of liver injury, according to the results of a recent study.

Between September 2004 and March 2013, 845 cases of liver injury were thought to be "definitely, highly likely, or probably" from an herbal or dietary supplement, or from prescription drugs. Of these cases, 136 (16%) were attributed to a product in the herbal and dietary supplement category. Patients reported consuming a total of 262 different herbal and dietary supplements; 30% were body-building products. Cases of liver injury from all herbal and dietary supplements increased from 7% in 2004-2005 to 20% in 2010-2012, reported Dr. Victor J. Navarro at the annual meeting of the American Association for the Study of Liver Diseases.

The prospective study used data from the Drug-Induced Liver Injury Network (DILIN). The network was established in 2003 by the National Institute of Diabetes and Digestive and Kidney Diseases to collect and analyze cases of severe liver injury caused by prescription and over-the-counter drugs, as well as alternative medications, including herbal products and supplements.

Of the hepatotoxicity cases due to supplements, 7 were excluded because they involved both body-building and other herbal and dietary supplements. Of the remaining 129 cases, 44 were attributed to body-building supplements and 85 cases were attributed to other types of herbal and dietary supplements. These cases were compared with 709 cases of drug-induced liver injury, noted Dr. Navarro, chair of the division of hepatology, Einstein Healthcare Network, Philadelphia.

Clinical features and demographic characteristics differed between the groups. The 44 patients with injury induced by body-building supplements were younger (mean age 33 years, vs. 48-50 years in the other two groups), and all were men. In the other two groups, 35%-37% of cases occurred in men.

As for clinical presentation, "the body-building supplement injury cases stood apart," as there was a "distinct presentation of prolonged jaundice," Dr. Navarro noted. "These patients tended to have fewer comorbid conditions," were heavier, and were "uniformly symptomatic." They all had jaundice, and 84% had pruritus. Of patients in the other herbal and dietary supplement group, 78% presented with jaundice and 48% presented with pruritus, compared with and 68% and 53%, respectively, of those with drug-induced liver injury.

Body-building liver injury cases required hospitalization more often, but no patients in this group died or had a liver transplant. There were deaths from all causes in the two other groups, but the differences were not significant. However, 13% of the cases of liver injury from other supplements resulted in a liver transplant, compared with 3% among the drug-induced liver injury group, a significant difference.

The higher transplant rate indicates that the hepatoxicity induced by non-body-building supplements "may be more severe" than injury induced by prescription drugs, Dr. Navarro observed.

Other marked differences between the groups included a serum total bilirubin that was significantly higher and persisted significantly longer in patients with liver injury from body-building supplements.

Although the study results indicate that hepatotoxicity due to herbal and dietary supplements is increasing, this was not a population-based study, and so "additional efforts to characterize the true burden of disease in the U.S. population are needed," and are being addressed by DILIN, Dr. Navarro said.

The National Institutes of Health sponsored the study. Dr. Navarro had no relevant disclosures. Information about DILIN is available here.

[email protected]