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Undiagnosed Diabetes Common in Women With Acute MI
ORLANDO – A fifth of women with an acute myocardial infarction have previously undiagnosed diabetes, according to results from a German registry that included 706 women.
The registry analysis also showed that prevalence of previously undiagnosed diabetes in women with a recent MI significantly exceeded the rate in men, Dr. Anselm K. Gitt said at the annual scientific sessions of the American Heart Association. And the 3-year outcome of women with an acute MI and newly diagnosed diabetes closely tracked the outcomes of women who survived an acute MI and had previously diagnosed diabetes. The 3-year mortality rate in both groups of women was about 30%, reported Dr. Gitt, a cardiologist at the Heart Center in Ludwigshafen, Germany, and vice director of the Myocardial Infarction Research Institute in Ludwigshafen.
Guidelines issued in 2007 by the European Society of Cardiology and the European Association for the Study of Diabetes recommended that physicians routinely perform an oral glucose tolerance test on patients following a MI who had not previously been diagnosed with diabetes (Eur. Heart J. 2007;28:88-136). "We started this study to see whether the recommendation had value in clinical practice. I think our new data confirm the recommendation," Dr. Gitt said.
However, because of results from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial, simply focusing on intensive glycemic control in post-MI patients with newly diagnosed diabetes is probably not an ideal management approach, he acknowledged. Although study results have not clearly established an optimal strategy, he suggested "good glycemic control with attention to avoiding hypoglycemia, along with aggressively treating cardiovascular risk factors such as lipids and hypertension."
Dr. Gitt and his associates tallied the prevalence of diabetes in acute MI patients with data collected in the SWEETHEART registry, which enrolled 2,767 patients within 24 hours of either an ST-elevation MI or non ST-elevation MI at 30 German centers, and then followed the patients for 3 years. The group included 706 women (26%), with an average age of 71 years, compared with an average age of 64 among the 2,061 enrolled men. The prevalence of previously diagnosed diabetes was 30% among the women, and 23% among the men.
All patients without a prior diagnosis of diabetes underwent assessment with an oral glucose tolerance test, following the recommendation made by the ESC and EASD in 2007. This identified an additional 20% of the women and 15% of the men with diabetes (a blood glucose level greater than 200 mg/dL 2 hours following the oral glucose challenge), as well as 18% of the women and 23% of the men with impaired glucose tolerance. The total 50% prevalence of both newly and previously diagnosed diabetes among the women who entered the study was significantly higher than the combined 38% prevalence rate among the men, Dr. Gitt said.
During hospitalization for the index acute MI, the mortality rate among both the women and men newly diagnosed with diabetes was about 3%, similar to the rate among those with previously diagnosed diabetes. Mortality among the women and men with newly identified impaired glucose tolerance ran 0.8% and 0.4%, respectively, while mortality among those with no diabetes or glucose impairment was 1.2% among women and 1.3% among men.
During the 3-year follow-up, mortality in the newly diagnosed women was 31%, and it was 22% among the men. This finding is "important," because it shows that once physicians diagnose diabetes in a recent MI patient "their risk is very high," Dr. Gitt said. In women with a prior diabetes diagnosis the 3-year mortality rate was 30%, while in men with previously identified diabetes the mortality rate was 35%. Men and women with either impaired glucose tolerance or no identified glucose metabolism disorder had substantially lower 3-year mortality rates than ranged from 11% to 13%.
Dr. Gitt has received research grants from, and has been a consultant to or served on the speakers bureau for, AstraZeneca, Bristol Myers Squibb, Essex, GlaxoSmithKline, Merck, MSD, Pfizer, Roche, Eli Lilly, Sanofi-Aventis, Schering Plough, and Servier. He said that he has received research grants from Abbott and Hexal, and that he has been a consultant to or served on a speakers bureau for Amgen, Daiichi Sankyo, Iroko, and Novo Nordisk.
ORLANDO – A fifth of women with an acute myocardial infarction have previously undiagnosed diabetes, according to results from a German registry that included 706 women.
The registry analysis also showed that prevalence of previously undiagnosed diabetes in women with a recent MI significantly exceeded the rate in men, Dr. Anselm K. Gitt said at the annual scientific sessions of the American Heart Association. And the 3-year outcome of women with an acute MI and newly diagnosed diabetes closely tracked the outcomes of women who survived an acute MI and had previously diagnosed diabetes. The 3-year mortality rate in both groups of women was about 30%, reported Dr. Gitt, a cardiologist at the Heart Center in Ludwigshafen, Germany, and vice director of the Myocardial Infarction Research Institute in Ludwigshafen.
Guidelines issued in 2007 by the European Society of Cardiology and the European Association for the Study of Diabetes recommended that physicians routinely perform an oral glucose tolerance test on patients following a MI who had not previously been diagnosed with diabetes (Eur. Heart J. 2007;28:88-136). "We started this study to see whether the recommendation had value in clinical practice. I think our new data confirm the recommendation," Dr. Gitt said.
However, because of results from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial, simply focusing on intensive glycemic control in post-MI patients with newly diagnosed diabetes is probably not an ideal management approach, he acknowledged. Although study results have not clearly established an optimal strategy, he suggested "good glycemic control with attention to avoiding hypoglycemia, along with aggressively treating cardiovascular risk factors such as lipids and hypertension."
Dr. Gitt and his associates tallied the prevalence of diabetes in acute MI patients with data collected in the SWEETHEART registry, which enrolled 2,767 patients within 24 hours of either an ST-elevation MI or non ST-elevation MI at 30 German centers, and then followed the patients for 3 years. The group included 706 women (26%), with an average age of 71 years, compared with an average age of 64 among the 2,061 enrolled men. The prevalence of previously diagnosed diabetes was 30% among the women, and 23% among the men.
All patients without a prior diagnosis of diabetes underwent assessment with an oral glucose tolerance test, following the recommendation made by the ESC and EASD in 2007. This identified an additional 20% of the women and 15% of the men with diabetes (a blood glucose level greater than 200 mg/dL 2 hours following the oral glucose challenge), as well as 18% of the women and 23% of the men with impaired glucose tolerance. The total 50% prevalence of both newly and previously diagnosed diabetes among the women who entered the study was significantly higher than the combined 38% prevalence rate among the men, Dr. Gitt said.
During hospitalization for the index acute MI, the mortality rate among both the women and men newly diagnosed with diabetes was about 3%, similar to the rate among those with previously diagnosed diabetes. Mortality among the women and men with newly identified impaired glucose tolerance ran 0.8% and 0.4%, respectively, while mortality among those with no diabetes or glucose impairment was 1.2% among women and 1.3% among men.
During the 3-year follow-up, mortality in the newly diagnosed women was 31%, and it was 22% among the men. This finding is "important," because it shows that once physicians diagnose diabetes in a recent MI patient "their risk is very high," Dr. Gitt said. In women with a prior diabetes diagnosis the 3-year mortality rate was 30%, while in men with previously identified diabetes the mortality rate was 35%. Men and women with either impaired glucose tolerance or no identified glucose metabolism disorder had substantially lower 3-year mortality rates than ranged from 11% to 13%.
Dr. Gitt has received research grants from, and has been a consultant to or served on the speakers bureau for, AstraZeneca, Bristol Myers Squibb, Essex, GlaxoSmithKline, Merck, MSD, Pfizer, Roche, Eli Lilly, Sanofi-Aventis, Schering Plough, and Servier. He said that he has received research grants from Abbott and Hexal, and that he has been a consultant to or served on a speakers bureau for Amgen, Daiichi Sankyo, Iroko, and Novo Nordisk.
ORLANDO – A fifth of women with an acute myocardial infarction have previously undiagnosed diabetes, according to results from a German registry that included 706 women.
The registry analysis also showed that prevalence of previously undiagnosed diabetes in women with a recent MI significantly exceeded the rate in men, Dr. Anselm K. Gitt said at the annual scientific sessions of the American Heart Association. And the 3-year outcome of women with an acute MI and newly diagnosed diabetes closely tracked the outcomes of women who survived an acute MI and had previously diagnosed diabetes. The 3-year mortality rate in both groups of women was about 30%, reported Dr. Gitt, a cardiologist at the Heart Center in Ludwigshafen, Germany, and vice director of the Myocardial Infarction Research Institute in Ludwigshafen.
Guidelines issued in 2007 by the European Society of Cardiology and the European Association for the Study of Diabetes recommended that physicians routinely perform an oral glucose tolerance test on patients following a MI who had not previously been diagnosed with diabetes (Eur. Heart J. 2007;28:88-136). "We started this study to see whether the recommendation had value in clinical practice. I think our new data confirm the recommendation," Dr. Gitt said.
However, because of results from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial, simply focusing on intensive glycemic control in post-MI patients with newly diagnosed diabetes is probably not an ideal management approach, he acknowledged. Although study results have not clearly established an optimal strategy, he suggested "good glycemic control with attention to avoiding hypoglycemia, along with aggressively treating cardiovascular risk factors such as lipids and hypertension."
Dr. Gitt and his associates tallied the prevalence of diabetes in acute MI patients with data collected in the SWEETHEART registry, which enrolled 2,767 patients within 24 hours of either an ST-elevation MI or non ST-elevation MI at 30 German centers, and then followed the patients for 3 years. The group included 706 women (26%), with an average age of 71 years, compared with an average age of 64 among the 2,061 enrolled men. The prevalence of previously diagnosed diabetes was 30% among the women, and 23% among the men.
All patients without a prior diagnosis of diabetes underwent assessment with an oral glucose tolerance test, following the recommendation made by the ESC and EASD in 2007. This identified an additional 20% of the women and 15% of the men with diabetes (a blood glucose level greater than 200 mg/dL 2 hours following the oral glucose challenge), as well as 18% of the women and 23% of the men with impaired glucose tolerance. The total 50% prevalence of both newly and previously diagnosed diabetes among the women who entered the study was significantly higher than the combined 38% prevalence rate among the men, Dr. Gitt said.
During hospitalization for the index acute MI, the mortality rate among both the women and men newly diagnosed with diabetes was about 3%, similar to the rate among those with previously diagnosed diabetes. Mortality among the women and men with newly identified impaired glucose tolerance ran 0.8% and 0.4%, respectively, while mortality among those with no diabetes or glucose impairment was 1.2% among women and 1.3% among men.
During the 3-year follow-up, mortality in the newly diagnosed women was 31%, and it was 22% among the men. This finding is "important," because it shows that once physicians diagnose diabetes in a recent MI patient "their risk is very high," Dr. Gitt said. In women with a prior diabetes diagnosis the 3-year mortality rate was 30%, while in men with previously identified diabetes the mortality rate was 35%. Men and women with either impaired glucose tolerance or no identified glucose metabolism disorder had substantially lower 3-year mortality rates than ranged from 11% to 13%.
Dr. Gitt has received research grants from, and has been a consultant to or served on the speakers bureau for, AstraZeneca, Bristol Myers Squibb, Essex, GlaxoSmithKline, Merck, MSD, Pfizer, Roche, Eli Lilly, Sanofi-Aventis, Schering Plough, and Servier. He said that he has received research grants from Abbott and Hexal, and that he has been a consultant to or served on a speakers bureau for Amgen, Daiichi Sankyo, Iroko, and Novo Nordisk.
FROM THE ANNUAL SCIENTIFIC SESSIONS OF THE AMERICAN HEART ASSOCIATION
Major Finding: Following an acute myocardial infarction, the prevalence of previously undiagnosed diabetes was 20% in women, 15% in men.
Data Source: Review of 706 women and 2,061 men with an acute myocardial infarction enrolled into the SWEETHEART registry at 30 centers in Germany.
Disclosures: Dr. Gitt has received research grants from, and has been a consultant to or served on the speakers bureau for, AstraZeneca, Bristol Myers Squibb, Essex, GlaxoSmithKline, Merck, MSD, Pfizer, Roche, Eli Lilly, Sanofi-Aventis, Schering Plough, and Servier. He said that he has received research grants from Abbott and Hexal, and that he has been a consultant to or served on a speakers bureau for Amgen, Daiichi Sankyo, Iroko, and Novo Nordisk.
Spontaneous Labor Best for Congenital Heart Disease
ORLANDO – Infants with congenital heart disease generally do not benefit from scheduled delivery by either induced labor or an elective cesarean delivery, based on a review of 329 infants managed recently at a single, U.S. referral center.
But despite a lack of documented benefit from scheduled delivery and the potential for impaired infant health from scheduled delivery, the practice appeared common in Southern California, with a significantly reduced rate of spontaneous labor and vaginal deliveries for infants with a prenatal diagnosis of congenital heart disease.
"We speculate that the potential advantages derived from the prenatal diagnosis of congenital heart disease and from a controlled delivery during regular hours may be offset by the known neonatal risks associated with unnatural delivery, such as impaired lung dynamics and impaired clearance of lung fluid following a cesarean section," said Dr. Luca U. Trento at the annual scientific sessions of the American Heart Association.
"In certain cases, for example, neonates expected to require emergency intervention shortly after birth such as a child with a restricted atrial septum, scheduled delivery may be indicated. Furthermore, a mother who lives a far distance from the delivery center is another reason to consider scheduled delivery. However, on the whole our data do not support empiric modification of the delivery plan based solely on prenatal diagnosis of congenital heart disease," said Dr. Trento, a pediatric cardiologist with Kaiser Permanente of Northern California in Roseville.
"Routine cesarean sections are probably detrimental to both the baby and the mother. We are not saying never do a scheduled delivery, but a fetal diagnosis of congenital heart disease is not enough reason to alter the delivery mode," he said. Dr. Trento reported data collected at Children’s Hospital Los Angeles that he analyzed when he was on staff there.
His retrospective analysis included 329 consecutive infants with congenital heart disease admitted to the hospital for a planned cardiac intervention during the first 30 days of life and with an identified mode of delivery. The delivery mode was spontaneous labor for 54%, scheduled cesarean delivery for 34%, and induced labor for 12%. The average gestation age of the infants in all three subgroups was about 38 weeks, their average birth weight was about 3,000 g, and their average APGAR scores were 7.5 at 1 minute and 8.5 at 5 minutes.
Prenatal diagnosis of congenital heart disease occurred for 45% of the infants. Among those delivered by spontaneous labor, 33% had a prenatal diagnosis; among children born by cesarean section, 51% had a prenatal diagnosis; and 80% of infants with an induced delivery had a prenatal diagnosis.
Among the 58 infants diagnosed prenatally who nonetheless were scheduled for delivery by spontaneous labor, 55% underwent vaginal delivery while 45% had a cesarean delivery. In contrast, among the 119 infants scheduled for delivery by spontaneous labor with their congenital disease unidentified prenatally, 73% underwent vaginal delivery and 27% converted to cesarean delivery. The difference between the two subgroups was statistically significant.
"A fetal diagnosis of congenital heart disease is not enough reason to alter the delivery mode."
"This demonstrates some sort of bias on the obstetric side when there is a known prenatal diagnosis of congenital heart disease that increases the rate of cesarean section," Dr. Trento said.
In a multivariate analysis, prenatal diagnosis of congenital heart disease linked with a statistically significant, 2.6-fold increased rate of scheduled delivery, either induction or cesarean. Other tested variables showed no linkage to scheduled delivery including the specific anatomic type of congenital heart disease, gestational age, or any extracardiac malformation.
A second analysis looked at a variety of outcomes among the infants studied, including rate of preoperative intubation, survival to surgery, duration of stay in the cardiothoracic intensive care unit, survival to postoperative discharge from the cardiothoracic intensive care unit, and survival to hospital discharge. This analysis revealed no statistically significant link between delivery mode and any of these outcomes. Other variables not linked with these outcomes included gestational age, being small for gestational age, a prenatal diagnosis of congenital heart disease, and delivery during "regular" hours of 8 a.m. to 6 p.m. Monday through Friday. The only significant predictor of survival to hospital discharge in a multivariate analysis was the infants’ risk adjusted congenital heart surgery score. Infants with a score of 3 or 4 had a 2.2-fold higher rate of surviving to hospital discharge, compared with infants with a score of 5 or 6.
Dr. Trento said that he had no disclosures.
ORLANDO – Infants with congenital heart disease generally do not benefit from scheduled delivery by either induced labor or an elective cesarean delivery, based on a review of 329 infants managed recently at a single, U.S. referral center.
But despite a lack of documented benefit from scheduled delivery and the potential for impaired infant health from scheduled delivery, the practice appeared common in Southern California, with a significantly reduced rate of spontaneous labor and vaginal deliveries for infants with a prenatal diagnosis of congenital heart disease.
"We speculate that the potential advantages derived from the prenatal diagnosis of congenital heart disease and from a controlled delivery during regular hours may be offset by the known neonatal risks associated with unnatural delivery, such as impaired lung dynamics and impaired clearance of lung fluid following a cesarean section," said Dr. Luca U. Trento at the annual scientific sessions of the American Heart Association.
"In certain cases, for example, neonates expected to require emergency intervention shortly after birth such as a child with a restricted atrial septum, scheduled delivery may be indicated. Furthermore, a mother who lives a far distance from the delivery center is another reason to consider scheduled delivery. However, on the whole our data do not support empiric modification of the delivery plan based solely on prenatal diagnosis of congenital heart disease," said Dr. Trento, a pediatric cardiologist with Kaiser Permanente of Northern California in Roseville.
"Routine cesarean sections are probably detrimental to both the baby and the mother. We are not saying never do a scheduled delivery, but a fetal diagnosis of congenital heart disease is not enough reason to alter the delivery mode," he said. Dr. Trento reported data collected at Children’s Hospital Los Angeles that he analyzed when he was on staff there.
His retrospective analysis included 329 consecutive infants with congenital heart disease admitted to the hospital for a planned cardiac intervention during the first 30 days of life and with an identified mode of delivery. The delivery mode was spontaneous labor for 54%, scheduled cesarean delivery for 34%, and induced labor for 12%. The average gestation age of the infants in all three subgroups was about 38 weeks, their average birth weight was about 3,000 g, and their average APGAR scores were 7.5 at 1 minute and 8.5 at 5 minutes.
Prenatal diagnosis of congenital heart disease occurred for 45% of the infants. Among those delivered by spontaneous labor, 33% had a prenatal diagnosis; among children born by cesarean section, 51% had a prenatal diagnosis; and 80% of infants with an induced delivery had a prenatal diagnosis.
Among the 58 infants diagnosed prenatally who nonetheless were scheduled for delivery by spontaneous labor, 55% underwent vaginal delivery while 45% had a cesarean delivery. In contrast, among the 119 infants scheduled for delivery by spontaneous labor with their congenital disease unidentified prenatally, 73% underwent vaginal delivery and 27% converted to cesarean delivery. The difference between the two subgroups was statistically significant.
"A fetal diagnosis of congenital heart disease is not enough reason to alter the delivery mode."
"This demonstrates some sort of bias on the obstetric side when there is a known prenatal diagnosis of congenital heart disease that increases the rate of cesarean section," Dr. Trento said.
In a multivariate analysis, prenatal diagnosis of congenital heart disease linked with a statistically significant, 2.6-fold increased rate of scheduled delivery, either induction or cesarean. Other tested variables showed no linkage to scheduled delivery including the specific anatomic type of congenital heart disease, gestational age, or any extracardiac malformation.
A second analysis looked at a variety of outcomes among the infants studied, including rate of preoperative intubation, survival to surgery, duration of stay in the cardiothoracic intensive care unit, survival to postoperative discharge from the cardiothoracic intensive care unit, and survival to hospital discharge. This analysis revealed no statistically significant link between delivery mode and any of these outcomes. Other variables not linked with these outcomes included gestational age, being small for gestational age, a prenatal diagnosis of congenital heart disease, and delivery during "regular" hours of 8 a.m. to 6 p.m. Monday through Friday. The only significant predictor of survival to hospital discharge in a multivariate analysis was the infants’ risk adjusted congenital heart surgery score. Infants with a score of 3 or 4 had a 2.2-fold higher rate of surviving to hospital discharge, compared with infants with a score of 5 or 6.
Dr. Trento said that he had no disclosures.
ORLANDO – Infants with congenital heart disease generally do not benefit from scheduled delivery by either induced labor or an elective cesarean delivery, based on a review of 329 infants managed recently at a single, U.S. referral center.
But despite a lack of documented benefit from scheduled delivery and the potential for impaired infant health from scheduled delivery, the practice appeared common in Southern California, with a significantly reduced rate of spontaneous labor and vaginal deliveries for infants with a prenatal diagnosis of congenital heart disease.
"We speculate that the potential advantages derived from the prenatal diagnosis of congenital heart disease and from a controlled delivery during regular hours may be offset by the known neonatal risks associated with unnatural delivery, such as impaired lung dynamics and impaired clearance of lung fluid following a cesarean section," said Dr. Luca U. Trento at the annual scientific sessions of the American Heart Association.
"In certain cases, for example, neonates expected to require emergency intervention shortly after birth such as a child with a restricted atrial septum, scheduled delivery may be indicated. Furthermore, a mother who lives a far distance from the delivery center is another reason to consider scheduled delivery. However, on the whole our data do not support empiric modification of the delivery plan based solely on prenatal diagnosis of congenital heart disease," said Dr. Trento, a pediatric cardiologist with Kaiser Permanente of Northern California in Roseville.
"Routine cesarean sections are probably detrimental to both the baby and the mother. We are not saying never do a scheduled delivery, but a fetal diagnosis of congenital heart disease is not enough reason to alter the delivery mode," he said. Dr. Trento reported data collected at Children’s Hospital Los Angeles that he analyzed when he was on staff there.
His retrospective analysis included 329 consecutive infants with congenital heart disease admitted to the hospital for a planned cardiac intervention during the first 30 days of life and with an identified mode of delivery. The delivery mode was spontaneous labor for 54%, scheduled cesarean delivery for 34%, and induced labor for 12%. The average gestation age of the infants in all three subgroups was about 38 weeks, their average birth weight was about 3,000 g, and their average APGAR scores were 7.5 at 1 minute and 8.5 at 5 minutes.
Prenatal diagnosis of congenital heart disease occurred for 45% of the infants. Among those delivered by spontaneous labor, 33% had a prenatal diagnosis; among children born by cesarean section, 51% had a prenatal diagnosis; and 80% of infants with an induced delivery had a prenatal diagnosis.
Among the 58 infants diagnosed prenatally who nonetheless were scheduled for delivery by spontaneous labor, 55% underwent vaginal delivery while 45% had a cesarean delivery. In contrast, among the 119 infants scheduled for delivery by spontaneous labor with their congenital disease unidentified prenatally, 73% underwent vaginal delivery and 27% converted to cesarean delivery. The difference between the two subgroups was statistically significant.
"A fetal diagnosis of congenital heart disease is not enough reason to alter the delivery mode."
"This demonstrates some sort of bias on the obstetric side when there is a known prenatal diagnosis of congenital heart disease that increases the rate of cesarean section," Dr. Trento said.
In a multivariate analysis, prenatal diagnosis of congenital heart disease linked with a statistically significant, 2.6-fold increased rate of scheduled delivery, either induction or cesarean. Other tested variables showed no linkage to scheduled delivery including the specific anatomic type of congenital heart disease, gestational age, or any extracardiac malformation.
A second analysis looked at a variety of outcomes among the infants studied, including rate of preoperative intubation, survival to surgery, duration of stay in the cardiothoracic intensive care unit, survival to postoperative discharge from the cardiothoracic intensive care unit, and survival to hospital discharge. This analysis revealed no statistically significant link between delivery mode and any of these outcomes. Other variables not linked with these outcomes included gestational age, being small for gestational age, a prenatal diagnosis of congenital heart disease, and delivery during "regular" hours of 8 a.m. to 6 p.m. Monday through Friday. The only significant predictor of survival to hospital discharge in a multivariate analysis was the infants’ risk adjusted congenital heart surgery score. Infants with a score of 3 or 4 had a 2.2-fold higher rate of surviving to hospital discharge, compared with infants with a score of 5 or 6.
Dr. Trento said that he had no disclosures.
FROM THE ANNUAL SCIENTIFIC SESSIONS OF THE AMERICAN HEART ASSOCIATION
Major Finding: Scheduled delivery by induced labor or elective cesarean section had no significant effect on outcomes in neonates born with congenital heart disease.
Data Source: Retrospective review of 329 consecutive infants with congenital heart disease referred to Children’s Hospital Los Angeles within the first 30 days of life.
Disclosures: Dr. Trento said that he had no disclosures.
Excessive Vitamin D Intake May Elevate A Fib Risk
ORLANDO – People with an excessive blood level of vitamin D from overdosing with supplements had a 2.5-fold increased incidence of atrial fibrillation, based on a study of 132,000 residents of Utah and southeastern Idaho.
The finding "suggests the need for caution with vitamin D supplementation and the need for careful assessment of serum levels if high doses [of vitamin D] are used," Megan B. Smith said at the annual scientific sessions of the American Heart Association.
The finding also suggests that patients identified with new-onset atrial fibrillation should be evaluated for a possible extremely high vitamin D level, said Ms. Smith, although in the results she reported, the high blood level of vitamin D linked with a significantly elevated incidence of atrial fibrillation, greater than 100 ng/dL, was extremely unusual, occurring in just 291 of the 132,000 people (0.2%) included in the study.
Although the mechanism linking such an extremely elevated blood level of vitamin D to a markedly increased rate of new-onset atrial fibrillation remains unclear, a likely explanation is the hypercalcemia that vitamin D toxicity can cause. Hypercalcemia can, in turn, reduce cardiac conduction velocity and shorten cardiac refractory time, said Ms. Smith, a dietician at Utah State University in Logan.
"Utah [residents have] tremendous use of supplements. From what we’ve seen in the charts we have, excessive use of vitamin D supplements is the primary driver" of the high levels seen, said Dr. T. Jared Bunch, director of electrophysiology research at the Intermountain Medical Group in Murray, Utah, and lead investigator for the study. "The few patients [with very high vitamin D levels] who I have seen got vitamin D in their milk, from a multivitamin, and from vitamin D pills. They get it from multiple sources," but added that the low prevalence of levels above 100 ng/dL also showed that it is a difficult level for a person to reach.
"Utah has an enormous problem with vitamin D deficiency, so we had this large group of people" who were members of Intermountain Healthcare, and had their vitamin D level measured once as part of their routine care. A survey by Dr. Bunch and his associates showed that unless asked, people don’t usually tell their physician that they take a vitamin D supplement, and that physicians at Intermountain Health do not usually ask patients about their vitamin D intake.
The measurement numbers documented the extent of the vitamin D deficiency problem, with 38,000 of the 132,000 people measured (29%) having a blood level below 20 ng/dL. This group with vitamin D deficiency showed significantly elevated prevalence rates of diabetes, hypertension, coronary artery disease, heart failure, and depression, compared with people in the designated "normal" vitamin D range of 41-60 ng/dL. But notably the incidence of atrial fibrillation in the deficiency group was not significantly different than the rate in the reference group with a normal vitamin D level at baseline.
"There is something unique" about the excess, toxic level, for atrial fibrillation incidence, Dr. Bunch said in an interview.
To better examine the potential role of vitamin D in elevating atrial fibrillation risk, Dr. Bunch and his associates are now regularly measuring blood vitamin D levels in Intermountain Healthcare members and prospectively tracking their atrial fibrillation incidence.
The results reported by Ms. Smith came from a retrospective analysis of the one-time vitamin D measurement by an immunoassay, and atrial fibrillation incidence tallied over an average 584 days of follow-up based on ECG testing and ICD-9 codes in each person’s medical record. The most common vitamin D level measured was 21-40 ng/dL, in 73,547 people (56%). Another 17,234 people (13%) had a level of 41-60 ng/dL, which the researchers considered normal and which they used as the reference group.
During follow-up, the incidence of new-onset atrial fibrillation was about 1.5% in all subgroups based on their baseline vitamin D level, except for those with a level above 100 ng/dL, who had an incidence of about 4%. A multivariate analysis that controlled for baseline differences in demographics identified a significantly elevated atrial fibrillation rate only in people with a baseline vitamin D level greater than 100 ng/dL.
Ms. Smith and Dr. Bunch said that they had no disclosures.
ORLANDO – People with an excessive blood level of vitamin D from overdosing with supplements had a 2.5-fold increased incidence of atrial fibrillation, based on a study of 132,000 residents of Utah and southeastern Idaho.
The finding "suggests the need for caution with vitamin D supplementation and the need for careful assessment of serum levels if high doses [of vitamin D] are used," Megan B. Smith said at the annual scientific sessions of the American Heart Association.
The finding also suggests that patients identified with new-onset atrial fibrillation should be evaluated for a possible extremely high vitamin D level, said Ms. Smith, although in the results she reported, the high blood level of vitamin D linked with a significantly elevated incidence of atrial fibrillation, greater than 100 ng/dL, was extremely unusual, occurring in just 291 of the 132,000 people (0.2%) included in the study.
Although the mechanism linking such an extremely elevated blood level of vitamin D to a markedly increased rate of new-onset atrial fibrillation remains unclear, a likely explanation is the hypercalcemia that vitamin D toxicity can cause. Hypercalcemia can, in turn, reduce cardiac conduction velocity and shorten cardiac refractory time, said Ms. Smith, a dietician at Utah State University in Logan.
"Utah [residents have] tremendous use of supplements. From what we’ve seen in the charts we have, excessive use of vitamin D supplements is the primary driver" of the high levels seen, said Dr. T. Jared Bunch, director of electrophysiology research at the Intermountain Medical Group in Murray, Utah, and lead investigator for the study. "The few patients [with very high vitamin D levels] who I have seen got vitamin D in their milk, from a multivitamin, and from vitamin D pills. They get it from multiple sources," but added that the low prevalence of levels above 100 ng/dL also showed that it is a difficult level for a person to reach.
"Utah has an enormous problem with vitamin D deficiency, so we had this large group of people" who were members of Intermountain Healthcare, and had their vitamin D level measured once as part of their routine care. A survey by Dr. Bunch and his associates showed that unless asked, people don’t usually tell their physician that they take a vitamin D supplement, and that physicians at Intermountain Health do not usually ask patients about their vitamin D intake.
The measurement numbers documented the extent of the vitamin D deficiency problem, with 38,000 of the 132,000 people measured (29%) having a blood level below 20 ng/dL. This group with vitamin D deficiency showed significantly elevated prevalence rates of diabetes, hypertension, coronary artery disease, heart failure, and depression, compared with people in the designated "normal" vitamin D range of 41-60 ng/dL. But notably the incidence of atrial fibrillation in the deficiency group was not significantly different than the rate in the reference group with a normal vitamin D level at baseline.
"There is something unique" about the excess, toxic level, for atrial fibrillation incidence, Dr. Bunch said in an interview.
To better examine the potential role of vitamin D in elevating atrial fibrillation risk, Dr. Bunch and his associates are now regularly measuring blood vitamin D levels in Intermountain Healthcare members and prospectively tracking their atrial fibrillation incidence.
The results reported by Ms. Smith came from a retrospective analysis of the one-time vitamin D measurement by an immunoassay, and atrial fibrillation incidence tallied over an average 584 days of follow-up based on ECG testing and ICD-9 codes in each person’s medical record. The most common vitamin D level measured was 21-40 ng/dL, in 73,547 people (56%). Another 17,234 people (13%) had a level of 41-60 ng/dL, which the researchers considered normal and which they used as the reference group.
During follow-up, the incidence of new-onset atrial fibrillation was about 1.5% in all subgroups based on their baseline vitamin D level, except for those with a level above 100 ng/dL, who had an incidence of about 4%. A multivariate analysis that controlled for baseline differences in demographics identified a significantly elevated atrial fibrillation rate only in people with a baseline vitamin D level greater than 100 ng/dL.
Ms. Smith and Dr. Bunch said that they had no disclosures.
ORLANDO – People with an excessive blood level of vitamin D from overdosing with supplements had a 2.5-fold increased incidence of atrial fibrillation, based on a study of 132,000 residents of Utah and southeastern Idaho.
The finding "suggests the need for caution with vitamin D supplementation and the need for careful assessment of serum levels if high doses [of vitamin D] are used," Megan B. Smith said at the annual scientific sessions of the American Heart Association.
The finding also suggests that patients identified with new-onset atrial fibrillation should be evaluated for a possible extremely high vitamin D level, said Ms. Smith, although in the results she reported, the high blood level of vitamin D linked with a significantly elevated incidence of atrial fibrillation, greater than 100 ng/dL, was extremely unusual, occurring in just 291 of the 132,000 people (0.2%) included in the study.
Although the mechanism linking such an extremely elevated blood level of vitamin D to a markedly increased rate of new-onset atrial fibrillation remains unclear, a likely explanation is the hypercalcemia that vitamin D toxicity can cause. Hypercalcemia can, in turn, reduce cardiac conduction velocity and shorten cardiac refractory time, said Ms. Smith, a dietician at Utah State University in Logan.
"Utah [residents have] tremendous use of supplements. From what we’ve seen in the charts we have, excessive use of vitamin D supplements is the primary driver" of the high levels seen, said Dr. T. Jared Bunch, director of electrophysiology research at the Intermountain Medical Group in Murray, Utah, and lead investigator for the study. "The few patients [with very high vitamin D levels] who I have seen got vitamin D in their milk, from a multivitamin, and from vitamin D pills. They get it from multiple sources," but added that the low prevalence of levels above 100 ng/dL also showed that it is a difficult level for a person to reach.
"Utah has an enormous problem with vitamin D deficiency, so we had this large group of people" who were members of Intermountain Healthcare, and had their vitamin D level measured once as part of their routine care. A survey by Dr. Bunch and his associates showed that unless asked, people don’t usually tell their physician that they take a vitamin D supplement, and that physicians at Intermountain Health do not usually ask patients about their vitamin D intake.
The measurement numbers documented the extent of the vitamin D deficiency problem, with 38,000 of the 132,000 people measured (29%) having a blood level below 20 ng/dL. This group with vitamin D deficiency showed significantly elevated prevalence rates of diabetes, hypertension, coronary artery disease, heart failure, and depression, compared with people in the designated "normal" vitamin D range of 41-60 ng/dL. But notably the incidence of atrial fibrillation in the deficiency group was not significantly different than the rate in the reference group with a normal vitamin D level at baseline.
"There is something unique" about the excess, toxic level, for atrial fibrillation incidence, Dr. Bunch said in an interview.
To better examine the potential role of vitamin D in elevating atrial fibrillation risk, Dr. Bunch and his associates are now regularly measuring blood vitamin D levels in Intermountain Healthcare members and prospectively tracking their atrial fibrillation incidence.
The results reported by Ms. Smith came from a retrospective analysis of the one-time vitamin D measurement by an immunoassay, and atrial fibrillation incidence tallied over an average 584 days of follow-up based on ECG testing and ICD-9 codes in each person’s medical record. The most common vitamin D level measured was 21-40 ng/dL, in 73,547 people (56%). Another 17,234 people (13%) had a level of 41-60 ng/dL, which the researchers considered normal and which they used as the reference group.
During follow-up, the incidence of new-onset atrial fibrillation was about 1.5% in all subgroups based on their baseline vitamin D level, except for those with a level above 100 ng/dL, who had an incidence of about 4%. A multivariate analysis that controlled for baseline differences in demographics identified a significantly elevated atrial fibrillation rate only in people with a baseline vitamin D level greater than 100 ng/dL.
Ms. Smith and Dr. Bunch said that they had no disclosures.
FROM THE ANNUAL SCIENTIFIC SESSIONS OF THE AMERICAN HEART ASSOCIATION
Major Finding: People with a vitamin D blood level above 100 ng/dL had a statistically significant 2.5-fold increased rate of atrial fibrillation during an average 584-day follow-up, compared with people who had a normal vitamin D level of 41-60 ng/dL.
Data Source: Review of 132,000 people who were members of Intermountain Healthcare in Utah or southeastern Idaho.
Disclosures: Ms. Smith and Dr. Bunch said that they had no disclosures.
Genotyping Guides Clopidogrel Dosing in CVD
ORLANDO – Genotyping can provide more targeted use of the commonly prescribed drug clopidogrel among patients with cardiovascular disease, according to data from the ELEVATE-TIMI 56 trial.
"We’re at the point that clopidogrel may not be a one-size-fits-all drug for our patients," Dr. Jessica Mega said at the annual scientific sessions of the American Heart Association.
She reported on the prospective ELEVATE-TIMI 56 trial involving 333 patients with stable cardiovascular disease who underwent genotyping for alleles of CYP2C19, which is primarily responsible for producing active metabolite from clopidogrel (Plavix). Research has shown that patients who carry nonfunctional alleles of CYP2C19 such as *2 have reduced plasma active metabolite levels, an increased risk of ex vivo residual platelet activity, and a greater risk of cardiac events such as stent thrombosis.
Based on the genotyping results, 86 carriers (80 heterozygotes and 6 homozygotes) of the CYP2C19*2 allele were randomized to daily clopidogrel doses of 75 mg, 150 mg, 225 mg, and 300 mg for four 14-day treatment periods, while 247 CYP2C19*2 noncarriers were assigned to daily clopidogrel 75 mg and 150 mg for two 14-day periods each.
Platelet testing at the end of each treatment period revealed that both CYP2C19*2 heterozygotes and homozygotes had significantly higher platelet reactivity than did noncarriers, said Dr. Mega, a cardiologist at Brigham and Women’s Hospital, Boston.
The mean vasodilator-stimulated phosphoprotein phosphorylation (VASP) platelet reactivity index (PRI) was 70% for carriers vs. 58% for noncarriers, while mean P2Y12 reaction units (PRUs) were 226 vs. 164, respectively.
Among CYP2C19*2 heterozygotes, tripling the daily maintenance dose of clopidogrel to 225 mg was needed to reduce platelet reactivity to the levels achieved with a standard 75-mg dose in noncarriers, she said. Specifically, the percentage of CYP2C19*2 heterozygotes who did not respond to standard dosing was reduced from 52% to 26% with a 150-mg dose, and to 10% with at least 225 mg of clopidogrel.
Among CYP2C19*2 homozygotes, who made up 2% of the study population, even 300 mg, or four times the standard dose, of clopidogrel did not result in optimal degrees of platelet inhibition.
Dr. Mega said alternative agents with higher degrees of platelet inhibition are available, but that clopidogrel will become generic next year and continues to be used in a significant number of patients.
"It’s good news for patients that we’re able to optimize their [platelet] inhibition with clopidogrel," she said. "I think we need to get creative in how we use clopidogrel, and this study is one step in the right direction."
Invited discussant Lawrence Lesko, Ph.D., director of the center for pharmacometrics and systems pharmacology at the University of Florida in Lake Nona, pointed out that clopidogrel carries a "black box" warning indicating that poor metabolizers are at heightened risk for cardiovascular events, and that ELEVATE-TIMI 56 fills in some of the gaps in the labeling of what to do with these patients as well as intermediate metabolizers.
"The results of this study point us in the direction of higher doses for the *1 and *2 genotypes to normalize them to the active metabolites of 75 mg," he said. "The most important open question in my mind after the study is, What do we do next to integrate genotyping more routinely into clinical practice for patients about to go on clopidogrel or already on clopidogrel?"
Dr. Mega responded that point of care tests are available that can be run by individuals in the catheter laboratory and deliver genotype results in 1 hour.
"So, I don’t think technology is going to be the rate-limiting step," she said.
In the study, VASP PRI was determined from blood samples sent to the Center for Platelet Research Studies in Boston. Platelet function testing was also conducted at each site using the point of care Verify Now P2Y12 test (Accumetrics).
ELEVATE-TIMI 56 included patients taking 75 mg clopidogrel for a myocardial infarction and/or undergoing percutaneous coronary intervention at least 4 weeks and not more than 6 months prior to study entry. Compliance during the study was 97.3% at the 75-mg dose, 98.1% at the 150-mg dose, 98.6% at the 225-mg dose, and 98.3% at the 300-mg dose. There were no deaths, cerebral events, or Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding events, Dr. Mega said.
The study was simultaneously published online (JAMA 2011 Nov. 16;306[doi:10.1001/jama.2011.1703]).
Bristol-Myers Squibb and Sanofi-Aventis sponsored the trial. Accumetrics and Nanosphere provided research supplies. Dr. Mega reported receiving grants from the National Institutes of Health. Dr. Lesko said he had no relevant financial disclosures.
ORLANDO – Genotyping can provide more targeted use of the commonly prescribed drug clopidogrel among patients with cardiovascular disease, according to data from the ELEVATE-TIMI 56 trial.
"We’re at the point that clopidogrel may not be a one-size-fits-all drug for our patients," Dr. Jessica Mega said at the annual scientific sessions of the American Heart Association.
She reported on the prospective ELEVATE-TIMI 56 trial involving 333 patients with stable cardiovascular disease who underwent genotyping for alleles of CYP2C19, which is primarily responsible for producing active metabolite from clopidogrel (Plavix). Research has shown that patients who carry nonfunctional alleles of CYP2C19 such as *2 have reduced plasma active metabolite levels, an increased risk of ex vivo residual platelet activity, and a greater risk of cardiac events such as stent thrombosis.
Based on the genotyping results, 86 carriers (80 heterozygotes and 6 homozygotes) of the CYP2C19*2 allele were randomized to daily clopidogrel doses of 75 mg, 150 mg, 225 mg, and 300 mg for four 14-day treatment periods, while 247 CYP2C19*2 noncarriers were assigned to daily clopidogrel 75 mg and 150 mg for two 14-day periods each.
Platelet testing at the end of each treatment period revealed that both CYP2C19*2 heterozygotes and homozygotes had significantly higher platelet reactivity than did noncarriers, said Dr. Mega, a cardiologist at Brigham and Women’s Hospital, Boston.
The mean vasodilator-stimulated phosphoprotein phosphorylation (VASP) platelet reactivity index (PRI) was 70% for carriers vs. 58% for noncarriers, while mean P2Y12 reaction units (PRUs) were 226 vs. 164, respectively.
Among CYP2C19*2 heterozygotes, tripling the daily maintenance dose of clopidogrel to 225 mg was needed to reduce platelet reactivity to the levels achieved with a standard 75-mg dose in noncarriers, she said. Specifically, the percentage of CYP2C19*2 heterozygotes who did not respond to standard dosing was reduced from 52% to 26% with a 150-mg dose, and to 10% with at least 225 mg of clopidogrel.
Among CYP2C19*2 homozygotes, who made up 2% of the study population, even 300 mg, or four times the standard dose, of clopidogrel did not result in optimal degrees of platelet inhibition.
Dr. Mega said alternative agents with higher degrees of platelet inhibition are available, but that clopidogrel will become generic next year and continues to be used in a significant number of patients.
"It’s good news for patients that we’re able to optimize their [platelet] inhibition with clopidogrel," she said. "I think we need to get creative in how we use clopidogrel, and this study is one step in the right direction."
Invited discussant Lawrence Lesko, Ph.D., director of the center for pharmacometrics and systems pharmacology at the University of Florida in Lake Nona, pointed out that clopidogrel carries a "black box" warning indicating that poor metabolizers are at heightened risk for cardiovascular events, and that ELEVATE-TIMI 56 fills in some of the gaps in the labeling of what to do with these patients as well as intermediate metabolizers.
"The results of this study point us in the direction of higher doses for the *1 and *2 genotypes to normalize them to the active metabolites of 75 mg," he said. "The most important open question in my mind after the study is, What do we do next to integrate genotyping more routinely into clinical practice for patients about to go on clopidogrel or already on clopidogrel?"
Dr. Mega responded that point of care tests are available that can be run by individuals in the catheter laboratory and deliver genotype results in 1 hour.
"So, I don’t think technology is going to be the rate-limiting step," she said.
In the study, VASP PRI was determined from blood samples sent to the Center for Platelet Research Studies in Boston. Platelet function testing was also conducted at each site using the point of care Verify Now P2Y12 test (Accumetrics).
ELEVATE-TIMI 56 included patients taking 75 mg clopidogrel for a myocardial infarction and/or undergoing percutaneous coronary intervention at least 4 weeks and not more than 6 months prior to study entry. Compliance during the study was 97.3% at the 75-mg dose, 98.1% at the 150-mg dose, 98.6% at the 225-mg dose, and 98.3% at the 300-mg dose. There were no deaths, cerebral events, or Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding events, Dr. Mega said.
The study was simultaneously published online (JAMA 2011 Nov. 16;306[doi:10.1001/jama.2011.1703]).
Bristol-Myers Squibb and Sanofi-Aventis sponsored the trial. Accumetrics and Nanosphere provided research supplies. Dr. Mega reported receiving grants from the National Institutes of Health. Dr. Lesko said he had no relevant financial disclosures.
ORLANDO – Genotyping can provide more targeted use of the commonly prescribed drug clopidogrel among patients with cardiovascular disease, according to data from the ELEVATE-TIMI 56 trial.
"We’re at the point that clopidogrel may not be a one-size-fits-all drug for our patients," Dr. Jessica Mega said at the annual scientific sessions of the American Heart Association.
She reported on the prospective ELEVATE-TIMI 56 trial involving 333 patients with stable cardiovascular disease who underwent genotyping for alleles of CYP2C19, which is primarily responsible for producing active metabolite from clopidogrel (Plavix). Research has shown that patients who carry nonfunctional alleles of CYP2C19 such as *2 have reduced plasma active metabolite levels, an increased risk of ex vivo residual platelet activity, and a greater risk of cardiac events such as stent thrombosis.
Based on the genotyping results, 86 carriers (80 heterozygotes and 6 homozygotes) of the CYP2C19*2 allele were randomized to daily clopidogrel doses of 75 mg, 150 mg, 225 mg, and 300 mg for four 14-day treatment periods, while 247 CYP2C19*2 noncarriers were assigned to daily clopidogrel 75 mg and 150 mg for two 14-day periods each.
Platelet testing at the end of each treatment period revealed that both CYP2C19*2 heterozygotes and homozygotes had significantly higher platelet reactivity than did noncarriers, said Dr. Mega, a cardiologist at Brigham and Women’s Hospital, Boston.
The mean vasodilator-stimulated phosphoprotein phosphorylation (VASP) platelet reactivity index (PRI) was 70% for carriers vs. 58% for noncarriers, while mean P2Y12 reaction units (PRUs) were 226 vs. 164, respectively.
Among CYP2C19*2 heterozygotes, tripling the daily maintenance dose of clopidogrel to 225 mg was needed to reduce platelet reactivity to the levels achieved with a standard 75-mg dose in noncarriers, she said. Specifically, the percentage of CYP2C19*2 heterozygotes who did not respond to standard dosing was reduced from 52% to 26% with a 150-mg dose, and to 10% with at least 225 mg of clopidogrel.
Among CYP2C19*2 homozygotes, who made up 2% of the study population, even 300 mg, or four times the standard dose, of clopidogrel did not result in optimal degrees of platelet inhibition.
Dr. Mega said alternative agents with higher degrees of platelet inhibition are available, but that clopidogrel will become generic next year and continues to be used in a significant number of patients.
"It’s good news for patients that we’re able to optimize their [platelet] inhibition with clopidogrel," she said. "I think we need to get creative in how we use clopidogrel, and this study is one step in the right direction."
Invited discussant Lawrence Lesko, Ph.D., director of the center for pharmacometrics and systems pharmacology at the University of Florida in Lake Nona, pointed out that clopidogrel carries a "black box" warning indicating that poor metabolizers are at heightened risk for cardiovascular events, and that ELEVATE-TIMI 56 fills in some of the gaps in the labeling of what to do with these patients as well as intermediate metabolizers.
"The results of this study point us in the direction of higher doses for the *1 and *2 genotypes to normalize them to the active metabolites of 75 mg," he said. "The most important open question in my mind after the study is, What do we do next to integrate genotyping more routinely into clinical practice for patients about to go on clopidogrel or already on clopidogrel?"
Dr. Mega responded that point of care tests are available that can be run by individuals in the catheter laboratory and deliver genotype results in 1 hour.
"So, I don’t think technology is going to be the rate-limiting step," she said.
In the study, VASP PRI was determined from blood samples sent to the Center for Platelet Research Studies in Boston. Platelet function testing was also conducted at each site using the point of care Verify Now P2Y12 test (Accumetrics).
ELEVATE-TIMI 56 included patients taking 75 mg clopidogrel for a myocardial infarction and/or undergoing percutaneous coronary intervention at least 4 weeks and not more than 6 months prior to study entry. Compliance during the study was 97.3% at the 75-mg dose, 98.1% at the 150-mg dose, 98.6% at the 225-mg dose, and 98.3% at the 300-mg dose. There were no deaths, cerebral events, or Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding events, Dr. Mega said.
The study was simultaneously published online (JAMA 2011 Nov. 16;306[doi:10.1001/jama.2011.1703]).
Bristol-Myers Squibb and Sanofi-Aventis sponsored the trial. Accumetrics and Nanosphere provided research supplies. Dr. Mega reported receiving grants from the National Institutes of Health. Dr. Lesko said he had no relevant financial disclosures.
FROM THE ANNUAL SCIENTIFIC SESSIONS OF THE AMERICAN HEART ASSOCIATION
Major Finding: The percentage of CYP2C19*2 heterozygotes with no response in platelet activity to standard clopidogrel dosing was reduced from 52% to 26% with a 150-mg dose, and to 10% with at least 225 mg of clopidogrel.
Data Source: ELEVATE-TIMI 56, a prospective, randomized double-blind trial in 333 patients with stable cardiovascular disease.
Disclosures: Bristol-Myers Squibb and Sanofi-Aventis sponsored the trial. Accumetrics and Nanosphere provided research supplies. Dr. Mega reported receiving grants from the National Institutes of Health. Dr. Lesko said he had no relevant financial disclosures.
Ramipril Improves Walking in Claudicants in RCT
ORLANDO – The ACE inhibitor ramipril boosted both walking ability and quality of life in patients with peripheral arterial disease in a double-blind, randomized trial.
This is the second randomized, placebo-controlled, double-blind study to show such effects, so it appears that the benefits are real.
And there’s more good news: "The magnitude of these effects is greater than that reported for conventional medical therapies," Dr. Anna A. Ahimastos observed when presenting the study findings at the annual scientific sessions of the American Heart Association.
She reported on 343 patients with peripheral arterial disease (PAD) who were randomized to 24 weeks of ramipril at 10 mg once daily or placebo. They averaged 65 years of age, 80% were men, the baseline ankle-brachial index was 0.56, and 36% had diabetes.
At 24 weeks, the average pain-free walking time (PFWT) in the ramipril group had increased by 87%, compared with a baseline of 131 seconds. The maximum walk time (MWT) improved by 139% from a baseline of 229 seconds. This corresponded to a clinically meaningful 172-meter increase in walking distance on a standardized treadmill test conducted at a speed of 3.2 km/hr and a 12% gradient, according to Dr. Ahimastos of the Baker IDI Heart and Diabetes Institute at Alfred Hospital in Melbourne.
In contrast, both PFWT and MWT decreased modestly over the course of 24 weeks in the control group.
A finding of particular importance in this impaired population with PAD was the documented improvement in quality of life that accompanied 24 weeks of ramipril, she continued. Daily functional capacity as measured by the WIQ (Walking Impairment Questionnaire) score domains of walking distance, speed, and stair climbing improved by 184%-213%. Scores on the SF-36 (36-Item Short Form) physical function component showed a significant 7% improvement from a baseline average of 38.5.
Results of this study are consistent with those of an earlier randomized, double-blind pilot study that Dr. Ahimastos and coworkers conducted in 40 patients (Ann. Intern. Med. 2006;144: 660-4).
Audience members who have grown accustomed to negative clinical trials being reported for PAD were enthusiastic at the prospect of finally gaining an additional effective medical therapy for this difficult condition.
The pilot study showed average gains of 164% in PFWT and 243% in MWT with 24 weeks of ramipril, a magnitude of benefit roughly twice that seen in the new, much larger trial. This is probably because the pilot study employed quite restrictive inclusion criteria, whereas the new study included a broader spectrum of PAD patients, including those with diabetes and with aortoiliac or infrainguinal disease.
Outcomes in the two randomized trials of ramipril for PAD – gains of 87%-164% in PFWT and 139%-243% in MWT – compare favorably with the results of placebo-controlled studies of conventional therapies. The phosphodiesterase-3 inhibitor cilostazol has shown 32%-82% improvements in PFWT and MWT. Pentoxifylline, another phosphodiesterase inhibitor, produced a 12% gain in MWT. And exercise training has shown a 150% improvement in both MWT and PFWT. However, the compliance rate with exercise is quite low in the PAD population, she noted.
Audience members who have grown accustomed to negative clinical trials being reported for PAD were enthusiastic at the prospect of finally gaining an additional effective medical therapy for this difficult condition. And they were curious as to Dr. Ahimastos’s thoughts on the mechanism of benefit.
She replied that at this point she can only speculate, since clinical trials don’t provide answers regarding mechanisms and the data from the new study were unblinded only the week prior to her presentation. She noted that ACE inhibitors have antiangiogenic and vasodilatory effects. The enhanced nitric oxide release and the drugs’ effects on bradykinin might also be relevant.
The improvement in walking doesn’t appear to stem from ramipril’s blood pressure–lowering effect, however, as the blood pressure reductions were minimal – less than 3 mm Hg in both systolic and diastolic blood pressure – and the degree of blood pressure reduction in individual patients didn’t correlate with their magnitude of walking improvement.
She and her colleagues don’t know whether angiotensin-receptor blockers would have similar clinical benefits on walking in PAD patients. That will prove difficult to study. For ethical reasons, future clinical trials are unlikely, as there is now evidence-based agreement among experts that patients with PAD should be on an ACE inhibitor or ARB anyway for cardiovascular protection.
The study was funded by Australia’s National Heart Foundation. Dr. Ahimastos declared having no financial conflicts.
ORLANDO – The ACE inhibitor ramipril boosted both walking ability and quality of life in patients with peripheral arterial disease in a double-blind, randomized trial.
This is the second randomized, placebo-controlled, double-blind study to show such effects, so it appears that the benefits are real.
And there’s more good news: "The magnitude of these effects is greater than that reported for conventional medical therapies," Dr. Anna A. Ahimastos observed when presenting the study findings at the annual scientific sessions of the American Heart Association.
She reported on 343 patients with peripheral arterial disease (PAD) who were randomized to 24 weeks of ramipril at 10 mg once daily or placebo. They averaged 65 years of age, 80% were men, the baseline ankle-brachial index was 0.56, and 36% had diabetes.
At 24 weeks, the average pain-free walking time (PFWT) in the ramipril group had increased by 87%, compared with a baseline of 131 seconds. The maximum walk time (MWT) improved by 139% from a baseline of 229 seconds. This corresponded to a clinically meaningful 172-meter increase in walking distance on a standardized treadmill test conducted at a speed of 3.2 km/hr and a 12% gradient, according to Dr. Ahimastos of the Baker IDI Heart and Diabetes Institute at Alfred Hospital in Melbourne.
In contrast, both PFWT and MWT decreased modestly over the course of 24 weeks in the control group.
A finding of particular importance in this impaired population with PAD was the documented improvement in quality of life that accompanied 24 weeks of ramipril, she continued. Daily functional capacity as measured by the WIQ (Walking Impairment Questionnaire) score domains of walking distance, speed, and stair climbing improved by 184%-213%. Scores on the SF-36 (36-Item Short Form) physical function component showed a significant 7% improvement from a baseline average of 38.5.
Results of this study are consistent with those of an earlier randomized, double-blind pilot study that Dr. Ahimastos and coworkers conducted in 40 patients (Ann. Intern. Med. 2006;144: 660-4).
Audience members who have grown accustomed to negative clinical trials being reported for PAD were enthusiastic at the prospect of finally gaining an additional effective medical therapy for this difficult condition.
The pilot study showed average gains of 164% in PFWT and 243% in MWT with 24 weeks of ramipril, a magnitude of benefit roughly twice that seen in the new, much larger trial. This is probably because the pilot study employed quite restrictive inclusion criteria, whereas the new study included a broader spectrum of PAD patients, including those with diabetes and with aortoiliac or infrainguinal disease.
Outcomes in the two randomized trials of ramipril for PAD – gains of 87%-164% in PFWT and 139%-243% in MWT – compare favorably with the results of placebo-controlled studies of conventional therapies. The phosphodiesterase-3 inhibitor cilostazol has shown 32%-82% improvements in PFWT and MWT. Pentoxifylline, another phosphodiesterase inhibitor, produced a 12% gain in MWT. And exercise training has shown a 150% improvement in both MWT and PFWT. However, the compliance rate with exercise is quite low in the PAD population, she noted.
Audience members who have grown accustomed to negative clinical trials being reported for PAD were enthusiastic at the prospect of finally gaining an additional effective medical therapy for this difficult condition. And they were curious as to Dr. Ahimastos’s thoughts on the mechanism of benefit.
She replied that at this point she can only speculate, since clinical trials don’t provide answers regarding mechanisms and the data from the new study were unblinded only the week prior to her presentation. She noted that ACE inhibitors have antiangiogenic and vasodilatory effects. The enhanced nitric oxide release and the drugs’ effects on bradykinin might also be relevant.
The improvement in walking doesn’t appear to stem from ramipril’s blood pressure–lowering effect, however, as the blood pressure reductions were minimal – less than 3 mm Hg in both systolic and diastolic blood pressure – and the degree of blood pressure reduction in individual patients didn’t correlate with their magnitude of walking improvement.
She and her colleagues don’t know whether angiotensin-receptor blockers would have similar clinical benefits on walking in PAD patients. That will prove difficult to study. For ethical reasons, future clinical trials are unlikely, as there is now evidence-based agreement among experts that patients with PAD should be on an ACE inhibitor or ARB anyway for cardiovascular protection.
The study was funded by Australia’s National Heart Foundation. Dr. Ahimastos declared having no financial conflicts.
ORLANDO – The ACE inhibitor ramipril boosted both walking ability and quality of life in patients with peripheral arterial disease in a double-blind, randomized trial.
This is the second randomized, placebo-controlled, double-blind study to show such effects, so it appears that the benefits are real.
And there’s more good news: "The magnitude of these effects is greater than that reported for conventional medical therapies," Dr. Anna A. Ahimastos observed when presenting the study findings at the annual scientific sessions of the American Heart Association.
She reported on 343 patients with peripheral arterial disease (PAD) who were randomized to 24 weeks of ramipril at 10 mg once daily or placebo. They averaged 65 years of age, 80% were men, the baseline ankle-brachial index was 0.56, and 36% had diabetes.
At 24 weeks, the average pain-free walking time (PFWT) in the ramipril group had increased by 87%, compared with a baseline of 131 seconds. The maximum walk time (MWT) improved by 139% from a baseline of 229 seconds. This corresponded to a clinically meaningful 172-meter increase in walking distance on a standardized treadmill test conducted at a speed of 3.2 km/hr and a 12% gradient, according to Dr. Ahimastos of the Baker IDI Heart and Diabetes Institute at Alfred Hospital in Melbourne.
In contrast, both PFWT and MWT decreased modestly over the course of 24 weeks in the control group.
A finding of particular importance in this impaired population with PAD was the documented improvement in quality of life that accompanied 24 weeks of ramipril, she continued. Daily functional capacity as measured by the WIQ (Walking Impairment Questionnaire) score domains of walking distance, speed, and stair climbing improved by 184%-213%. Scores on the SF-36 (36-Item Short Form) physical function component showed a significant 7% improvement from a baseline average of 38.5.
Results of this study are consistent with those of an earlier randomized, double-blind pilot study that Dr. Ahimastos and coworkers conducted in 40 patients (Ann. Intern. Med. 2006;144: 660-4).
Audience members who have grown accustomed to negative clinical trials being reported for PAD were enthusiastic at the prospect of finally gaining an additional effective medical therapy for this difficult condition.
The pilot study showed average gains of 164% in PFWT and 243% in MWT with 24 weeks of ramipril, a magnitude of benefit roughly twice that seen in the new, much larger trial. This is probably because the pilot study employed quite restrictive inclusion criteria, whereas the new study included a broader spectrum of PAD patients, including those with diabetes and with aortoiliac or infrainguinal disease.
Outcomes in the two randomized trials of ramipril for PAD – gains of 87%-164% in PFWT and 139%-243% in MWT – compare favorably with the results of placebo-controlled studies of conventional therapies. The phosphodiesterase-3 inhibitor cilostazol has shown 32%-82% improvements in PFWT and MWT. Pentoxifylline, another phosphodiesterase inhibitor, produced a 12% gain in MWT. And exercise training has shown a 150% improvement in both MWT and PFWT. However, the compliance rate with exercise is quite low in the PAD population, she noted.
Audience members who have grown accustomed to negative clinical trials being reported for PAD were enthusiastic at the prospect of finally gaining an additional effective medical therapy for this difficult condition. And they were curious as to Dr. Ahimastos’s thoughts on the mechanism of benefit.
She replied that at this point she can only speculate, since clinical trials don’t provide answers regarding mechanisms and the data from the new study were unblinded only the week prior to her presentation. She noted that ACE inhibitors have antiangiogenic and vasodilatory effects. The enhanced nitric oxide release and the drugs’ effects on bradykinin might also be relevant.
The improvement in walking doesn’t appear to stem from ramipril’s blood pressure–lowering effect, however, as the blood pressure reductions were minimal – less than 3 mm Hg in both systolic and diastolic blood pressure – and the degree of blood pressure reduction in individual patients didn’t correlate with their magnitude of walking improvement.
She and her colleagues don’t know whether angiotensin-receptor blockers would have similar clinical benefits on walking in PAD patients. That will prove difficult to study. For ethical reasons, future clinical trials are unlikely, as there is now evidence-based agreement among experts that patients with PAD should be on an ACE inhibitor or ARB anyway for cardiovascular protection.
The study was funded by Australia’s National Heart Foundation. Dr. Ahimastos declared having no financial conflicts.
FROM THE ANNUAL SCIENTIFIC SESSIONS OF THE AMERICAN HEART ASSOCIATION
Major Finding: A 24-week regimen of ramipril resulted in an average 87% improvement in pain-free walking time, a 139% gain in maximum walking time, and significantly enhanced quality of life in patients with peripheral artery disease.
Data Source: A double-blind, placebo-controlled, randomized clinical trial in 343 PAD patients.
Disclosures: No financial conflicts were declared.
For Most With Diabetes, Revascularization Can Wait
ORLANDO – Virtually no patients with type 2 diabetes and documented coronary artery disease and coronary ischemia benefit from immediate coronary revascularization, as long as they receive intensive medical management, based on the outcomes of more than 1,000 patients who were randomized to the deferred revascularization arm of the BARI 2D trial.
The only possible exception to this approach are the rare patients who initially present with severe or unstable angina and proximal left anterior descending (LAD) artery disease, a small group accounting for just 2% of these patients, Dr. Ronald J. Krone said at the annual scientific sessions of the American Heart Association. Even in this small subgroup with the worst chance of avoiding revascularization, eventual coronary bypass surgery or percutaneous coronary intervention (PCI) is not an absolute. Among the 21 patients with this initial presentation at study entry (of the total 1,192 who were randomized to the deferred revascularization arm), 50% continued to avoid revascularization 6 months later, and 29% had still not undergone revascularization 5 years after the study began, said Dr. Krone, an interventional cardiologist and professor of medicine at Washington University, St. Louis.
"What it comes down to is that there is no group you can identify up front" that unequivocally needs immediate revascularization," Dr. Krone said in an interview. "We could not identify patients who will need revascularization at a high enough rate to warrant initial revascularization, with the possible exception" of the small proximal LAD and severe angina subgroup. "Even in the worst patients, you can intervene later. We used to be afraid that if we didn’t [revascularize these patients] they would drop dead or have a big myocardial infarction, but that didn’t happen. These results give us confidence that you don’t need to intervene on every tight lesion."
Today, a physician or surgeon can’t say "’I have to revascularize, because it’s the best I can do’" for these patients. Instead, the onus is to intensively treat these patients medically, especially patients with diabetes, Dr. Krone said. This strategy includes optimal control of hypertension, lipids, glycemia, and intensive lifestyle intervention with exercise, diet, and smoking cessation.
The analysis he presented focused on patients enrolled in the BARI 2D (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes), which randomized a total of 2,368 patients with diabetes and documented coronary ischemia and stenosis suitable for an elective intervention. The researchers put all these patients on an intensive medical management regimen, and also randomized them to either immediate or deferred revascularization. The study’s primary results showed absolutely identical 5-year outcomes in the two groups, with a mortality rate of 12% in each arm of the study, and a combined rate of death, MI, or stroke of 23% in the immediate revascularization patients and 24% in those with deferred intervention (N. Engl. J. Med. 2009;360:2503-15).
Among the 1,192 patients in the deferred subgroup, 13% required PCI or bypass surgery after 6 months, and 40% needed revascularization after 5 years of follow-up. Within the group who eventually had revascularization, 47% required it for worsening angina, 23% because of an acute coronary syndrome event, 18% for worsening ischemia, 6% for progression of their coronary disease, and the remaining 6% for another reason. The current analysis aimed to determine whether "we can identify patients with such a high likelihood of needing revascularization that it need not be deferred," Dr. Krone said.
The average age of the patients in the deferred revascularization group was 62 years; 30% were women, 28% were on insulin treatment, 17% had a left ventricular ejection fraction below 50%, and 13% had proximal LAD coronary disease. Their average duration of type 2 diabetes was 11 years.
A multivariate analysis that controlled for age, sex, race, and nationality identified five factors that were linked with a significantly increased rate of revascularization after 6 months: class III or IV stable angina, unstable angina, a systolic blood pressure of 100 mm Hg or less, a blood triglyceride level of 100 mg/dL or less, and proximal LAD disease. These factors were linked with anywhere from a 3.8-fold increased rate of revascularization (in patients with systolic hypotension, compared with patients with a systolic pressure greater than 100 mm Hg) to a 75% increased rate (in patients with proximal LAD disease, compared with those without LAD disease). However, none of these increased rates appeared to justify performing routine, upfront revascularization.
The 5-year multivariate analysis produced similar results. It identified nine baseline factors that each significantly linked with a significantly increased rate of revascularization during 5-year follow-up: class I or II stable angina, class III or IV stable angina, unstable angina, systolic blood pressure of 101-120 mm Hg, a systolic pressure of 100 mm HG or less, a blood triglyceride level of 100 mg/dL or greater, proximal LAD disease, having two diseased coronary regions, or having three diseased coronary regions. The increased rates associated with these features ranged from a 90% increased revascularization rate (in patients with class III or IV stable angina, compared with patients without angina), to a 28% increased revascularization rate (in patients with class I or II stable angina at baseline). Again, none of these increased rates appeared to justify uniform, upfront revascularization, Dr. Krone said.
The sole exception to this approach might possibly be the small number of patients who initially presented with both proximal LAD disease and either class III or IV stable angina or unstable angina, because eventually over 5 years 71% of these patients underwent revascularization. But these patients constituted only 2% of the total group studied, Dr. Krone noted. In general, more severe angina or stenosis was uncommon in these patients: Some 41% had no angina and 45% had class I or II angina at baseline, and 87% were free of proximal LAD disease at baseline.
Dr. Krone said that he had no disclosures.
ORLANDO – Virtually no patients with type 2 diabetes and documented coronary artery disease and coronary ischemia benefit from immediate coronary revascularization, as long as they receive intensive medical management, based on the outcomes of more than 1,000 patients who were randomized to the deferred revascularization arm of the BARI 2D trial.
The only possible exception to this approach are the rare patients who initially present with severe or unstable angina and proximal left anterior descending (LAD) artery disease, a small group accounting for just 2% of these patients, Dr. Ronald J. Krone said at the annual scientific sessions of the American Heart Association. Even in this small subgroup with the worst chance of avoiding revascularization, eventual coronary bypass surgery or percutaneous coronary intervention (PCI) is not an absolute. Among the 21 patients with this initial presentation at study entry (of the total 1,192 who were randomized to the deferred revascularization arm), 50% continued to avoid revascularization 6 months later, and 29% had still not undergone revascularization 5 years after the study began, said Dr. Krone, an interventional cardiologist and professor of medicine at Washington University, St. Louis.
"What it comes down to is that there is no group you can identify up front" that unequivocally needs immediate revascularization," Dr. Krone said in an interview. "We could not identify patients who will need revascularization at a high enough rate to warrant initial revascularization, with the possible exception" of the small proximal LAD and severe angina subgroup. "Even in the worst patients, you can intervene later. We used to be afraid that if we didn’t [revascularize these patients] they would drop dead or have a big myocardial infarction, but that didn’t happen. These results give us confidence that you don’t need to intervene on every tight lesion."
Today, a physician or surgeon can’t say "’I have to revascularize, because it’s the best I can do’" for these patients. Instead, the onus is to intensively treat these patients medically, especially patients with diabetes, Dr. Krone said. This strategy includes optimal control of hypertension, lipids, glycemia, and intensive lifestyle intervention with exercise, diet, and smoking cessation.
The analysis he presented focused on patients enrolled in the BARI 2D (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes), which randomized a total of 2,368 patients with diabetes and documented coronary ischemia and stenosis suitable for an elective intervention. The researchers put all these patients on an intensive medical management regimen, and also randomized them to either immediate or deferred revascularization. The study’s primary results showed absolutely identical 5-year outcomes in the two groups, with a mortality rate of 12% in each arm of the study, and a combined rate of death, MI, or stroke of 23% in the immediate revascularization patients and 24% in those with deferred intervention (N. Engl. J. Med. 2009;360:2503-15).
Among the 1,192 patients in the deferred subgroup, 13% required PCI or bypass surgery after 6 months, and 40% needed revascularization after 5 years of follow-up. Within the group who eventually had revascularization, 47% required it for worsening angina, 23% because of an acute coronary syndrome event, 18% for worsening ischemia, 6% for progression of their coronary disease, and the remaining 6% for another reason. The current analysis aimed to determine whether "we can identify patients with such a high likelihood of needing revascularization that it need not be deferred," Dr. Krone said.
The average age of the patients in the deferred revascularization group was 62 years; 30% were women, 28% were on insulin treatment, 17% had a left ventricular ejection fraction below 50%, and 13% had proximal LAD coronary disease. Their average duration of type 2 diabetes was 11 years.
A multivariate analysis that controlled for age, sex, race, and nationality identified five factors that were linked with a significantly increased rate of revascularization after 6 months: class III or IV stable angina, unstable angina, a systolic blood pressure of 100 mm Hg or less, a blood triglyceride level of 100 mg/dL or less, and proximal LAD disease. These factors were linked with anywhere from a 3.8-fold increased rate of revascularization (in patients with systolic hypotension, compared with patients with a systolic pressure greater than 100 mm Hg) to a 75% increased rate (in patients with proximal LAD disease, compared with those without LAD disease). However, none of these increased rates appeared to justify performing routine, upfront revascularization.
The 5-year multivariate analysis produced similar results. It identified nine baseline factors that each significantly linked with a significantly increased rate of revascularization during 5-year follow-up: class I or II stable angina, class III or IV stable angina, unstable angina, systolic blood pressure of 101-120 mm Hg, a systolic pressure of 100 mm HG or less, a blood triglyceride level of 100 mg/dL or greater, proximal LAD disease, having two diseased coronary regions, or having three diseased coronary regions. The increased rates associated with these features ranged from a 90% increased revascularization rate (in patients with class III or IV stable angina, compared with patients without angina), to a 28% increased revascularization rate (in patients with class I or II stable angina at baseline). Again, none of these increased rates appeared to justify uniform, upfront revascularization, Dr. Krone said.
The sole exception to this approach might possibly be the small number of patients who initially presented with both proximal LAD disease and either class III or IV stable angina or unstable angina, because eventually over 5 years 71% of these patients underwent revascularization. But these patients constituted only 2% of the total group studied, Dr. Krone noted. In general, more severe angina or stenosis was uncommon in these patients: Some 41% had no angina and 45% had class I or II angina at baseline, and 87% were free of proximal LAD disease at baseline.
Dr. Krone said that he had no disclosures.
ORLANDO – Virtually no patients with type 2 diabetes and documented coronary artery disease and coronary ischemia benefit from immediate coronary revascularization, as long as they receive intensive medical management, based on the outcomes of more than 1,000 patients who were randomized to the deferred revascularization arm of the BARI 2D trial.
The only possible exception to this approach are the rare patients who initially present with severe or unstable angina and proximal left anterior descending (LAD) artery disease, a small group accounting for just 2% of these patients, Dr. Ronald J. Krone said at the annual scientific sessions of the American Heart Association. Even in this small subgroup with the worst chance of avoiding revascularization, eventual coronary bypass surgery or percutaneous coronary intervention (PCI) is not an absolute. Among the 21 patients with this initial presentation at study entry (of the total 1,192 who were randomized to the deferred revascularization arm), 50% continued to avoid revascularization 6 months later, and 29% had still not undergone revascularization 5 years after the study began, said Dr. Krone, an interventional cardiologist and professor of medicine at Washington University, St. Louis.
"What it comes down to is that there is no group you can identify up front" that unequivocally needs immediate revascularization," Dr. Krone said in an interview. "We could not identify patients who will need revascularization at a high enough rate to warrant initial revascularization, with the possible exception" of the small proximal LAD and severe angina subgroup. "Even in the worst patients, you can intervene later. We used to be afraid that if we didn’t [revascularize these patients] they would drop dead or have a big myocardial infarction, but that didn’t happen. These results give us confidence that you don’t need to intervene on every tight lesion."
Today, a physician or surgeon can’t say "’I have to revascularize, because it’s the best I can do’" for these patients. Instead, the onus is to intensively treat these patients medically, especially patients with diabetes, Dr. Krone said. This strategy includes optimal control of hypertension, lipids, glycemia, and intensive lifestyle intervention with exercise, diet, and smoking cessation.
The analysis he presented focused on patients enrolled in the BARI 2D (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes), which randomized a total of 2,368 patients with diabetes and documented coronary ischemia and stenosis suitable for an elective intervention. The researchers put all these patients on an intensive medical management regimen, and also randomized them to either immediate or deferred revascularization. The study’s primary results showed absolutely identical 5-year outcomes in the two groups, with a mortality rate of 12% in each arm of the study, and a combined rate of death, MI, or stroke of 23% in the immediate revascularization patients and 24% in those with deferred intervention (N. Engl. J. Med. 2009;360:2503-15).
Among the 1,192 patients in the deferred subgroup, 13% required PCI or bypass surgery after 6 months, and 40% needed revascularization after 5 years of follow-up. Within the group who eventually had revascularization, 47% required it for worsening angina, 23% because of an acute coronary syndrome event, 18% for worsening ischemia, 6% for progression of their coronary disease, and the remaining 6% for another reason. The current analysis aimed to determine whether "we can identify patients with such a high likelihood of needing revascularization that it need not be deferred," Dr. Krone said.
The average age of the patients in the deferred revascularization group was 62 years; 30% were women, 28% were on insulin treatment, 17% had a left ventricular ejection fraction below 50%, and 13% had proximal LAD coronary disease. Their average duration of type 2 diabetes was 11 years.
A multivariate analysis that controlled for age, sex, race, and nationality identified five factors that were linked with a significantly increased rate of revascularization after 6 months: class III or IV stable angina, unstable angina, a systolic blood pressure of 100 mm Hg or less, a blood triglyceride level of 100 mg/dL or less, and proximal LAD disease. These factors were linked with anywhere from a 3.8-fold increased rate of revascularization (in patients with systolic hypotension, compared with patients with a systolic pressure greater than 100 mm Hg) to a 75% increased rate (in patients with proximal LAD disease, compared with those without LAD disease). However, none of these increased rates appeared to justify performing routine, upfront revascularization.
The 5-year multivariate analysis produced similar results. It identified nine baseline factors that each significantly linked with a significantly increased rate of revascularization during 5-year follow-up: class I or II stable angina, class III or IV stable angina, unstable angina, systolic blood pressure of 101-120 mm Hg, a systolic pressure of 100 mm HG or less, a blood triglyceride level of 100 mg/dL or greater, proximal LAD disease, having two diseased coronary regions, or having three diseased coronary regions. The increased rates associated with these features ranged from a 90% increased revascularization rate (in patients with class III or IV stable angina, compared with patients without angina), to a 28% increased revascularization rate (in patients with class I or II stable angina at baseline). Again, none of these increased rates appeared to justify uniform, upfront revascularization, Dr. Krone said.
The sole exception to this approach might possibly be the small number of patients who initially presented with both proximal LAD disease and either class III or IV stable angina or unstable angina, because eventually over 5 years 71% of these patients underwent revascularization. But these patients constituted only 2% of the total group studied, Dr. Krone noted. In general, more severe angina or stenosis was uncommon in these patients: Some 41% had no angina and 45% had class I or II angina at baseline, and 87% were free of proximal LAD disease at baseline.
Dr. Krone said that he had no disclosures.
FROM THE ANNUAL SCIENTIFIC SESSIONS OF THE AMERICAN HEART ASSOCIATION
Major Finding: Few patients with diabetes and documented ischemic coronary disease suitable for elective revascularization have features that predict a high risk for eventually requiring a procedure during the subsequent 5 years. The only possible exception is the 2% of patients with both proximal LAD coronary disease and severe or unstable angina at baseline, who had a 71% revascularization rate.
Data Source: A subgroup analysis of the BARI 2D study, which randomized 2,368 patients with type 2 diabetes and documented ischemic coronary disease suitable for elective revascularization to an immediate or deferred procedure. The new analysis focused on 1,192 patients initially randomized to the delayed revascularization arm.
Disclosures: Dr. Krone said that he had no disclosures.
Colchicine Nearly Halves Post-Op Atrial Fib Risk
ORLANDO – The gout medication colchicine nearly halved the incidence of postoperative atrial fibrillation after cardiac surgery in a substudy of the Colchicine for the Prevention of the Postpericardiotomy Syndrome trial.
The incidence of atrial fibrillation (AF) between postoperative days 3 and 30 was 12% with colchicine (Colcrys) vs. 22% with placebo (P value = .021), or a relative risk reduction of 46%.
"Though I don’t recommend the routine use of colchicine for the prevention of postoperative atrial fibrillation on the basis of a single trial, ... colchicine as [empirical] anti-inflammatory therapy appears to be an inexpensive and safe means to reduce the incidence of postoperative atrial fibrillation, hospitalization length of stay, and the incidence of postpericardiotomy syndrome and postoperative effusions," principal investigator Dr. Massimo Imazio said at the annual scientific sessions of the American Heart Association.
Colchicine was approved in the United States in 2007 for gout, but is not registered for the prevention of pericarditis in North America or Europe. The study was simultaneously published online (Circulation 2011 Nov. 16 [doi:10.1161/CIRCULATIONAHA.111.026153]).
Invited discussant Dr. Nancy Nussmeier, director of anesthesia at the State University of New York, Syracuse, said that the substudy has practical and useful implications. She pointed out, however, that COPPS was conducted in a relatively healthy, adult, white population, and that colchicine was started on postoperative day 3, thereby missing early postoperative atrial fibrillation (POAF) cases on postoperative days 1 and 2. Notably, 43% of the 97 POAF episodes occurred on postoperative days 1 and 2 before colchicine was started. Gastrointestinal intolerance, largely diarrhea, may also limit widespread use of the drug, she said.
Dr. Nussmeier called for larger multicenter trials to confirm the efficacy of colchicine and said that future research should address earlier administration, the possibility of preoperative administration, or administration as an adjunct for the treatment and prevention of recurrent POAF after it develops.
Dr. Imazio observed that the ability of colchicine to halve the mean duration of POAF may also be particularly important for reducing the subsequent rate of late AF more than 30 days after surgery, because a longer duration of POAF is a strong and independent predictor of late AF.
COPPS randomized 360 patients undergoing cardiac surgery at six hospitals in northern Italy to placebo or colchicine 1.0 mg twice-daily for 1 month in those weighing 70 kg or more and 0.5 mg in those less than 70 kg or intolerant to the higher dose.
Data previously reported from COPPS at the European Society of Cardiology meeting showed that colchicine significantly reduced the relative risk of postpericardiotomy syndrome (PPS) by 57.9%, with a number-needed-to treat of eight (Eur. Heart J. 2010;31:2749-54).
Among the 250 patients included in the substudy, the number needed to treat to prevent one case of POAF was 11, said Dr. Imazio of the Maria Vittoria Hospital in Turin, Italy.
Patients who were given colchicine, compared with those given placebo, had shorter cardiac surgery hospital stays (9.3 days vs. 10.3 days), rehabilitation stays (12.1 days vs. 13.9 days), and overall hospital stays (defined as both cardiac plus rehabilitation stays; 21.4 days vs. 24.2 days). The rate of death or stroke was identical in both groups at 1.2%.
Side effects were reported in 16 patients in the colchicine group and in 8 in the placebo group, and were driven entirely by gastrointestinal events in the colchicine group, he said. Side effects contributed to drug withdrawal in 16 of 20 patients in the colchicine group and in 8 of 11 withdrawals in the placebo group.
In multivariate analysis, patients with POAF were significantly more likely to have a left atrial anteroposterior diameter of more than 45 mm, to have undergone surgery other than cardiac bypass surgery, and to have pericardial effusion. Those without POAF were more likely to have had perioperative beta-blockade and to have been treated with colchicine, Dr. Imazio said.
In multivariate adjusted analyses, only left atrial anteroposterior diameter remained significant for POAF development (hazard ratio, 2.31), whereas the use of colchicine (HR, 0.52) and perioperative beta blockade (HR, 0.47) remained significantly protective.
Acarpia Lda supplied the drug for the trial. Dr. Imazio reported no conflicts. Dr. Nussmeier reported serving as a consultant/advisor to Merck.
ORLANDO – The gout medication colchicine nearly halved the incidence of postoperative atrial fibrillation after cardiac surgery in a substudy of the Colchicine for the Prevention of the Postpericardiotomy Syndrome trial.
The incidence of atrial fibrillation (AF) between postoperative days 3 and 30 was 12% with colchicine (Colcrys) vs. 22% with placebo (P value = .021), or a relative risk reduction of 46%.
"Though I don’t recommend the routine use of colchicine for the prevention of postoperative atrial fibrillation on the basis of a single trial, ... colchicine as [empirical] anti-inflammatory therapy appears to be an inexpensive and safe means to reduce the incidence of postoperative atrial fibrillation, hospitalization length of stay, and the incidence of postpericardiotomy syndrome and postoperative effusions," principal investigator Dr. Massimo Imazio said at the annual scientific sessions of the American Heart Association.
Colchicine was approved in the United States in 2007 for gout, but is not registered for the prevention of pericarditis in North America or Europe. The study was simultaneously published online (Circulation 2011 Nov. 16 [doi:10.1161/CIRCULATIONAHA.111.026153]).
Invited discussant Dr. Nancy Nussmeier, director of anesthesia at the State University of New York, Syracuse, said that the substudy has practical and useful implications. She pointed out, however, that COPPS was conducted in a relatively healthy, adult, white population, and that colchicine was started on postoperative day 3, thereby missing early postoperative atrial fibrillation (POAF) cases on postoperative days 1 and 2. Notably, 43% of the 97 POAF episodes occurred on postoperative days 1 and 2 before colchicine was started. Gastrointestinal intolerance, largely diarrhea, may also limit widespread use of the drug, she said.
Dr. Nussmeier called for larger multicenter trials to confirm the efficacy of colchicine and said that future research should address earlier administration, the possibility of preoperative administration, or administration as an adjunct for the treatment and prevention of recurrent POAF after it develops.
Dr. Imazio observed that the ability of colchicine to halve the mean duration of POAF may also be particularly important for reducing the subsequent rate of late AF more than 30 days after surgery, because a longer duration of POAF is a strong and independent predictor of late AF.
COPPS randomized 360 patients undergoing cardiac surgery at six hospitals in northern Italy to placebo or colchicine 1.0 mg twice-daily for 1 month in those weighing 70 kg or more and 0.5 mg in those less than 70 kg or intolerant to the higher dose.
Data previously reported from COPPS at the European Society of Cardiology meeting showed that colchicine significantly reduced the relative risk of postpericardiotomy syndrome (PPS) by 57.9%, with a number-needed-to treat of eight (Eur. Heart J. 2010;31:2749-54).
Among the 250 patients included in the substudy, the number needed to treat to prevent one case of POAF was 11, said Dr. Imazio of the Maria Vittoria Hospital in Turin, Italy.
Patients who were given colchicine, compared with those given placebo, had shorter cardiac surgery hospital stays (9.3 days vs. 10.3 days), rehabilitation stays (12.1 days vs. 13.9 days), and overall hospital stays (defined as both cardiac plus rehabilitation stays; 21.4 days vs. 24.2 days). The rate of death or stroke was identical in both groups at 1.2%.
Side effects were reported in 16 patients in the colchicine group and in 8 in the placebo group, and were driven entirely by gastrointestinal events in the colchicine group, he said. Side effects contributed to drug withdrawal in 16 of 20 patients in the colchicine group and in 8 of 11 withdrawals in the placebo group.
In multivariate analysis, patients with POAF were significantly more likely to have a left atrial anteroposterior diameter of more than 45 mm, to have undergone surgery other than cardiac bypass surgery, and to have pericardial effusion. Those without POAF were more likely to have had perioperative beta-blockade and to have been treated with colchicine, Dr. Imazio said.
In multivariate adjusted analyses, only left atrial anteroposterior diameter remained significant for POAF development (hazard ratio, 2.31), whereas the use of colchicine (HR, 0.52) and perioperative beta blockade (HR, 0.47) remained significantly protective.
Acarpia Lda supplied the drug for the trial. Dr. Imazio reported no conflicts. Dr. Nussmeier reported serving as a consultant/advisor to Merck.
ORLANDO – The gout medication colchicine nearly halved the incidence of postoperative atrial fibrillation after cardiac surgery in a substudy of the Colchicine for the Prevention of the Postpericardiotomy Syndrome trial.
The incidence of atrial fibrillation (AF) between postoperative days 3 and 30 was 12% with colchicine (Colcrys) vs. 22% with placebo (P value = .021), or a relative risk reduction of 46%.
"Though I don’t recommend the routine use of colchicine for the prevention of postoperative atrial fibrillation on the basis of a single trial, ... colchicine as [empirical] anti-inflammatory therapy appears to be an inexpensive and safe means to reduce the incidence of postoperative atrial fibrillation, hospitalization length of stay, and the incidence of postpericardiotomy syndrome and postoperative effusions," principal investigator Dr. Massimo Imazio said at the annual scientific sessions of the American Heart Association.
Colchicine was approved in the United States in 2007 for gout, but is not registered for the prevention of pericarditis in North America or Europe. The study was simultaneously published online (Circulation 2011 Nov. 16 [doi:10.1161/CIRCULATIONAHA.111.026153]).
Invited discussant Dr. Nancy Nussmeier, director of anesthesia at the State University of New York, Syracuse, said that the substudy has practical and useful implications. She pointed out, however, that COPPS was conducted in a relatively healthy, adult, white population, and that colchicine was started on postoperative day 3, thereby missing early postoperative atrial fibrillation (POAF) cases on postoperative days 1 and 2. Notably, 43% of the 97 POAF episodes occurred on postoperative days 1 and 2 before colchicine was started. Gastrointestinal intolerance, largely diarrhea, may also limit widespread use of the drug, she said.
Dr. Nussmeier called for larger multicenter trials to confirm the efficacy of colchicine and said that future research should address earlier administration, the possibility of preoperative administration, or administration as an adjunct for the treatment and prevention of recurrent POAF after it develops.
Dr. Imazio observed that the ability of colchicine to halve the mean duration of POAF may also be particularly important for reducing the subsequent rate of late AF more than 30 days after surgery, because a longer duration of POAF is a strong and independent predictor of late AF.
COPPS randomized 360 patients undergoing cardiac surgery at six hospitals in northern Italy to placebo or colchicine 1.0 mg twice-daily for 1 month in those weighing 70 kg or more and 0.5 mg in those less than 70 kg or intolerant to the higher dose.
Data previously reported from COPPS at the European Society of Cardiology meeting showed that colchicine significantly reduced the relative risk of postpericardiotomy syndrome (PPS) by 57.9%, with a number-needed-to treat of eight (Eur. Heart J. 2010;31:2749-54).
Among the 250 patients included in the substudy, the number needed to treat to prevent one case of POAF was 11, said Dr. Imazio of the Maria Vittoria Hospital in Turin, Italy.
Patients who were given colchicine, compared with those given placebo, had shorter cardiac surgery hospital stays (9.3 days vs. 10.3 days), rehabilitation stays (12.1 days vs. 13.9 days), and overall hospital stays (defined as both cardiac plus rehabilitation stays; 21.4 days vs. 24.2 days). The rate of death or stroke was identical in both groups at 1.2%.
Side effects were reported in 16 patients in the colchicine group and in 8 in the placebo group, and were driven entirely by gastrointestinal events in the colchicine group, he said. Side effects contributed to drug withdrawal in 16 of 20 patients in the colchicine group and in 8 of 11 withdrawals in the placebo group.
In multivariate analysis, patients with POAF were significantly more likely to have a left atrial anteroposterior diameter of more than 45 mm, to have undergone surgery other than cardiac bypass surgery, and to have pericardial effusion. Those without POAF were more likely to have had perioperative beta-blockade and to have been treated with colchicine, Dr. Imazio said.
In multivariate adjusted analyses, only left atrial anteroposterior diameter remained significant for POAF development (hazard ratio, 2.31), whereas the use of colchicine (HR, 0.52) and perioperative beta blockade (HR, 0.47) remained significantly protective.
Acarpia Lda supplied the drug for the trial. Dr. Imazio reported no conflicts. Dr. Nussmeier reported serving as a consultant/advisor to Merck.
FROM THE ANNUAL SCIENTIFIC SESSIONS OF THE AMERICAN HEART ASSOCIATION
Major Finding: The incidence of AF between postoperative days 3 and 30 was 12% with colchicine vs. 22% with placebo, for a statistically significant relative risk reduction of 46%.
Data Source: A substudy of the COPPS trial in 250 adults undergoing cardiac surgery.
Disclosures: Acarpia Lda supplied the drug for the trial. Dr. Imazio reported no conflicts. Dr. Nussmeier reported serving as a consultant/advisor to Merck.
AIM-HIGH Study Stirs Niacin Controversy
ORLANDO – Adding extended-release niacin to raise HDL cholesterol levels in patients with stable coronary heart disease who are maintaining their LDL cholesterol below 70 mg/dL with intensive statin therapy doesn’t further reduce their cardiovascular event risk, according to the large National Institutes of Heath–sponsored AIM-HIGH trial.
But enthusiasm at the annual scientific sessions of the American Heart Association was low for AIM-HIGH, despite its lofty name. Numerous critics pointed to study design flaws they said render the findings tough to interpret.
"This trial disturbs me greatly," said discussant Dr. Philip Barter of the Heart Research Institute in Sydney.
"Whatever conclusions are drawn from this trial, it cannot be emphasized too much that [the trial] has not tested the HDL hypothesis, nor was it powered sufficiently to test the potential benefits of adding niacin to statins," he added.
The AIM-HIGH trial (Niacin Plus Statins to Prevent Vascular Events) involved 3,414 patients with stable coronary artery disease and low HDL cholesterol levels who were placed on 40-80 mg/day of simvastatin supplemented as necessary by 10 mg/day of ezetimibe in order to maintain an LDL cholesterol level of 40-80 mg/dL.
Participants were randomized to 1,500-2,000 mg/day of extended-release niacin (Niaspan) or placebo to see if niacin plus simvastatin reduced cardiovascular events to a greater extent than did the statin alone. The primary end point was a composite of MI, ischemic stroke, death due to coronary heart disease, hospitalization for an acute coronary syndrome, or symptom-driven revascularization.
Niacin produced the anticipated favorable lipid changes: a 25% boost in HDL cholesterol at 2 years from a baseline median of 35 mg/dL, a 29% drop in triglycerides, and a 12% decrease in LDL cholesterol from a baseline of 74 mg/dL.
Yet AIM-HIGH was stopped early on the grounds of futility: After a mean 3 years of follow-up, the rate of the primary end point was 16.4% in the niacin group and nearly identical at 16.2% in controls.
"I think the take-away message from the study would be that if you – as a patient with stable, nonacute cardiac disease – are able to achieve and maintain the levels of LDL we got in this study (that is, in the 60s), then there is not evidence from this trial to support continued use of niacin for the purpose of reducing clinical events," said Dr. William E. Boden, lead researcher and professor of medicine and public health at the State University of New York at Buffalo.
Dr. Barter wasn’t buying it.
"I totally disagree with that interpretation," he said. "I do not believe that we should draw any conclusions or change clinical practice on the basis of this underpowered study. We really must not overreact to a trial that had no ability to answer the question."
"Fortunately, the value of adding niacin to effective statin therapy is currently being investigated in the very much larger [HPS2-THRIVE (Heart Protection Study 2 – Treatment of HDL to Reduce the Incidence of Vascular Events) trial] that has randomized more than 25,000 participants. Within the next 12-18 months we’ll have that result. If that study doesn’t show a positive effect, niacin is finished. But to prejudge that before we’ve got the results of that trial and to stop patients from being treated on niacin is, I think, in the public health disinterest," Dr. Barter said.
A major problem with AIM-HIGH, according to Dr. Eliot Brinton, was the investigators’ decision to incorporate 150-200 mg/day of immediate-release niacin into the placebo tablets so the control group would experience niacin-induced flushing and thus wouldn’t be able to tell which study arm they were in.
That decision may explain the average 9.8% increase in HDL cholesterol seen in the control arm. As a result of this unanticipated rise in HDL, the difference in HDL levels between the two study arms was a mere 4 mg/dL, which could account for the closely similar outcomes in the two groups.
"My suggestion, with all due respect to the people who worked very hard on AIM-HIGH, is that we not try to draw clinical conclusions based on this study that was, in many ways, rather complicated," said Dr. Brinton of the University of Utah, Salt Lake City.
"I do not believe that we should draw any conclusions or change clinical practice on the basis of this underpowered study."
Niacin has multiple beneficial metabolic effects in addition to being the most effective HDL-raising agent approved at present. It reduces levels of the highly atherogenic lipoprotein (a), triglycerides, and LDL cholesterol, and – in combination with statin therapy – it has been shown in angiographic studies to cause atherosclerotic plaque regression. While awaiting the results of HPS2-THRIVE, clinicians might want to continue to offer niacin therapy to patients who appear to be at residual risk of events because of low HDL levels, despite effective LDL-lowering therapy, he suggested.
"Talk to your patients. If they’re high risk and they want more treatment, then you consider it. We don’t force niacin. It’s not mandated. I think that’s where we are at the moment. Maybe a year or two from now, we’ll have some better answers," he said.
Simultaneously with Dr. Boden’s detailed presentation of the AIM-HIGH results in a late-breaking-trials session at the AHA meeting, the study was published online (N. Engl. J. Med. 2011 Nov. 15 [doi:10.1056/NEJMoa1107579]).
The AIM-HIGH study was funded by the National Heart, Lung, and Blood Institute and an unrestricted grant from Abbott Laboratories. Dr. Boden disclosed having received consulting fees from the company. Dr. Barter and Dr. Brinton declared having no financial conflicts.
ORLANDO – Adding extended-release niacin to raise HDL cholesterol levels in patients with stable coronary heart disease who are maintaining their LDL cholesterol below 70 mg/dL with intensive statin therapy doesn’t further reduce their cardiovascular event risk, according to the large National Institutes of Heath–sponsored AIM-HIGH trial.
But enthusiasm at the annual scientific sessions of the American Heart Association was low for AIM-HIGH, despite its lofty name. Numerous critics pointed to study design flaws they said render the findings tough to interpret.
"This trial disturbs me greatly," said discussant Dr. Philip Barter of the Heart Research Institute in Sydney.
"Whatever conclusions are drawn from this trial, it cannot be emphasized too much that [the trial] has not tested the HDL hypothesis, nor was it powered sufficiently to test the potential benefits of adding niacin to statins," he added.
The AIM-HIGH trial (Niacin Plus Statins to Prevent Vascular Events) involved 3,414 patients with stable coronary artery disease and low HDL cholesterol levels who were placed on 40-80 mg/day of simvastatin supplemented as necessary by 10 mg/day of ezetimibe in order to maintain an LDL cholesterol level of 40-80 mg/dL.
Participants were randomized to 1,500-2,000 mg/day of extended-release niacin (Niaspan) or placebo to see if niacin plus simvastatin reduced cardiovascular events to a greater extent than did the statin alone. The primary end point was a composite of MI, ischemic stroke, death due to coronary heart disease, hospitalization for an acute coronary syndrome, or symptom-driven revascularization.
Niacin produced the anticipated favorable lipid changes: a 25% boost in HDL cholesterol at 2 years from a baseline median of 35 mg/dL, a 29% drop in triglycerides, and a 12% decrease in LDL cholesterol from a baseline of 74 mg/dL.
Yet AIM-HIGH was stopped early on the grounds of futility: After a mean 3 years of follow-up, the rate of the primary end point was 16.4% in the niacin group and nearly identical at 16.2% in controls.
"I think the take-away message from the study would be that if you – as a patient with stable, nonacute cardiac disease – are able to achieve and maintain the levels of LDL we got in this study (that is, in the 60s), then there is not evidence from this trial to support continued use of niacin for the purpose of reducing clinical events," said Dr. William E. Boden, lead researcher and professor of medicine and public health at the State University of New York at Buffalo.
Dr. Barter wasn’t buying it.
"I totally disagree with that interpretation," he said. "I do not believe that we should draw any conclusions or change clinical practice on the basis of this underpowered study. We really must not overreact to a trial that had no ability to answer the question."
"Fortunately, the value of adding niacin to effective statin therapy is currently being investigated in the very much larger [HPS2-THRIVE (Heart Protection Study 2 – Treatment of HDL to Reduce the Incidence of Vascular Events) trial] that has randomized more than 25,000 participants. Within the next 12-18 months we’ll have that result. If that study doesn’t show a positive effect, niacin is finished. But to prejudge that before we’ve got the results of that trial and to stop patients from being treated on niacin is, I think, in the public health disinterest," Dr. Barter said.
A major problem with AIM-HIGH, according to Dr. Eliot Brinton, was the investigators’ decision to incorporate 150-200 mg/day of immediate-release niacin into the placebo tablets so the control group would experience niacin-induced flushing and thus wouldn’t be able to tell which study arm they were in.
That decision may explain the average 9.8% increase in HDL cholesterol seen in the control arm. As a result of this unanticipated rise in HDL, the difference in HDL levels between the two study arms was a mere 4 mg/dL, which could account for the closely similar outcomes in the two groups.
"My suggestion, with all due respect to the people who worked very hard on AIM-HIGH, is that we not try to draw clinical conclusions based on this study that was, in many ways, rather complicated," said Dr. Brinton of the University of Utah, Salt Lake City.
"I do not believe that we should draw any conclusions or change clinical practice on the basis of this underpowered study."
Niacin has multiple beneficial metabolic effects in addition to being the most effective HDL-raising agent approved at present. It reduces levels of the highly atherogenic lipoprotein (a), triglycerides, and LDL cholesterol, and – in combination with statin therapy – it has been shown in angiographic studies to cause atherosclerotic plaque regression. While awaiting the results of HPS2-THRIVE, clinicians might want to continue to offer niacin therapy to patients who appear to be at residual risk of events because of low HDL levels, despite effective LDL-lowering therapy, he suggested.
"Talk to your patients. If they’re high risk and they want more treatment, then you consider it. We don’t force niacin. It’s not mandated. I think that’s where we are at the moment. Maybe a year or two from now, we’ll have some better answers," he said.
Simultaneously with Dr. Boden’s detailed presentation of the AIM-HIGH results in a late-breaking-trials session at the AHA meeting, the study was published online (N. Engl. J. Med. 2011 Nov. 15 [doi:10.1056/NEJMoa1107579]).
The AIM-HIGH study was funded by the National Heart, Lung, and Blood Institute and an unrestricted grant from Abbott Laboratories. Dr. Boden disclosed having received consulting fees from the company. Dr. Barter and Dr. Brinton declared having no financial conflicts.
ORLANDO – Adding extended-release niacin to raise HDL cholesterol levels in patients with stable coronary heart disease who are maintaining their LDL cholesterol below 70 mg/dL with intensive statin therapy doesn’t further reduce their cardiovascular event risk, according to the large National Institutes of Heath–sponsored AIM-HIGH trial.
But enthusiasm at the annual scientific sessions of the American Heart Association was low for AIM-HIGH, despite its lofty name. Numerous critics pointed to study design flaws they said render the findings tough to interpret.
"This trial disturbs me greatly," said discussant Dr. Philip Barter of the Heart Research Institute in Sydney.
"Whatever conclusions are drawn from this trial, it cannot be emphasized too much that [the trial] has not tested the HDL hypothesis, nor was it powered sufficiently to test the potential benefits of adding niacin to statins," he added.
The AIM-HIGH trial (Niacin Plus Statins to Prevent Vascular Events) involved 3,414 patients with stable coronary artery disease and low HDL cholesterol levels who were placed on 40-80 mg/day of simvastatin supplemented as necessary by 10 mg/day of ezetimibe in order to maintain an LDL cholesterol level of 40-80 mg/dL.
Participants were randomized to 1,500-2,000 mg/day of extended-release niacin (Niaspan) or placebo to see if niacin plus simvastatin reduced cardiovascular events to a greater extent than did the statin alone. The primary end point was a composite of MI, ischemic stroke, death due to coronary heart disease, hospitalization for an acute coronary syndrome, or symptom-driven revascularization.
Niacin produced the anticipated favorable lipid changes: a 25% boost in HDL cholesterol at 2 years from a baseline median of 35 mg/dL, a 29% drop in triglycerides, and a 12% decrease in LDL cholesterol from a baseline of 74 mg/dL.
Yet AIM-HIGH was stopped early on the grounds of futility: After a mean 3 years of follow-up, the rate of the primary end point was 16.4% in the niacin group and nearly identical at 16.2% in controls.
"I think the take-away message from the study would be that if you – as a patient with stable, nonacute cardiac disease – are able to achieve and maintain the levels of LDL we got in this study (that is, in the 60s), then there is not evidence from this trial to support continued use of niacin for the purpose of reducing clinical events," said Dr. William E. Boden, lead researcher and professor of medicine and public health at the State University of New York at Buffalo.
Dr. Barter wasn’t buying it.
"I totally disagree with that interpretation," he said. "I do not believe that we should draw any conclusions or change clinical practice on the basis of this underpowered study. We really must not overreact to a trial that had no ability to answer the question."
"Fortunately, the value of adding niacin to effective statin therapy is currently being investigated in the very much larger [HPS2-THRIVE (Heart Protection Study 2 – Treatment of HDL to Reduce the Incidence of Vascular Events) trial] that has randomized more than 25,000 participants. Within the next 12-18 months we’ll have that result. If that study doesn’t show a positive effect, niacin is finished. But to prejudge that before we’ve got the results of that trial and to stop patients from being treated on niacin is, I think, in the public health disinterest," Dr. Barter said.
A major problem with AIM-HIGH, according to Dr. Eliot Brinton, was the investigators’ decision to incorporate 150-200 mg/day of immediate-release niacin into the placebo tablets so the control group would experience niacin-induced flushing and thus wouldn’t be able to tell which study arm they were in.
That decision may explain the average 9.8% increase in HDL cholesterol seen in the control arm. As a result of this unanticipated rise in HDL, the difference in HDL levels between the two study arms was a mere 4 mg/dL, which could account for the closely similar outcomes in the two groups.
"My suggestion, with all due respect to the people who worked very hard on AIM-HIGH, is that we not try to draw clinical conclusions based on this study that was, in many ways, rather complicated," said Dr. Brinton of the University of Utah, Salt Lake City.
"I do not believe that we should draw any conclusions or change clinical practice on the basis of this underpowered study."
Niacin has multiple beneficial metabolic effects in addition to being the most effective HDL-raising agent approved at present. It reduces levels of the highly atherogenic lipoprotein (a), triglycerides, and LDL cholesterol, and – in combination with statin therapy – it has been shown in angiographic studies to cause atherosclerotic plaque regression. While awaiting the results of HPS2-THRIVE, clinicians might want to continue to offer niacin therapy to patients who appear to be at residual risk of events because of low HDL levels, despite effective LDL-lowering therapy, he suggested.
"Talk to your patients. If they’re high risk and they want more treatment, then you consider it. We don’t force niacin. It’s not mandated. I think that’s where we are at the moment. Maybe a year or two from now, we’ll have some better answers," he said.
Simultaneously with Dr. Boden’s detailed presentation of the AIM-HIGH results in a late-breaking-trials session at the AHA meeting, the study was published online (N. Engl. J. Med. 2011 Nov. 15 [doi:10.1056/NEJMoa1107579]).
The AIM-HIGH study was funded by the National Heart, Lung, and Blood Institute and an unrestricted grant from Abbott Laboratories. Dr. Boden disclosed having received consulting fees from the company. Dr. Barter and Dr. Brinton declared having no financial conflicts.
FROM THE ANNUAL SCIENTIFIC SESSIONS OF THE AMERICAN HEART ASSOCIATION
Major Finding: Cardiovascular events occurred in 16.2% of patients with stable established CHD and low baseline HDL cholesterol whose LDL cholesterol was lowered to below 70 mg/dL through intensive statin therapy, and in a nearly identical 16.4% of patients randomized to receive in addition extended-release niacin.
Data Source: The 3,414-patient, randomized AIM-HIGH trial, which was stopped early due to futility.
Disclosures: The trial was funded by the NHLBI and Abbott Laboratories. Dr. Boden disclosed having received consulting fees from the company. Dr. Barter and Dr. Brinton declared having no financial conflicts.
CETP Inhibitor Evacetrapib Scores Big in Cholesterol Battle
ORLANDO – The investigational drug evacetrapib produced dramatic lipid effects with no major safety signals when used as monotherapy or in combination with statin therapy in a phase II randomized trial.
Monotherapy with the cholesteryl ester transfer protein (CETP) inhibitor produced a dose-dependent increase in HDL cholesterol that ranged from 53.6% to 128.8%.
LDL cholesterol levels decreased in a similar fashion from 13.6% to 35.9%, Dr. Stephen J. Nicholls reported at the annual scientific sessions of the American Heart Association.
When evacetrapib, at a dosage of 100 mg, was combined with commonly prescribed statins, LDL cholesterol levels fell significantly, by 46% with simvastatin (Zocor) 40 mg, 48% with atorvastatin (Lipitor), and 52% with rosuvastatin (Crestor) 10 mg. At the same doses, HDL cholesterol levels were increased by 87%, 80%, and 94%, respectively, all highly significant differences.
"This translated to an additional lowering of LDL cholesterol by 32% to 42% in addition to statin therapy," he said.
The data are comparable with those recently achieved by two other CETP inhibitors under investigation, anacetrapib and dalcetrapib. Interestingly, evacetrapib at 500 mg had a similar effect as anacetrapib 100 mg on HDL-C (129% vs. 138%) and LDL-C (136% vs. –40%), but appeared to have a greater impact on triglycerides (–17% vs. –7%), observed Dr. Daniel Rader, who was invited to discuss the paper.
The lack of any major safety signal is encouraging for CETP inhibitors as a class given the early problems surrounding torcetrapib, but that data are still needed from clinical outcome trials to determine whether CETP inhibition can reduce cardiovascular risk, said Dr. Rader, chief of translational medicine and human genetics and director of the preventive cardiovascular program at the University of Pennsylvania, Philadelphia.
"This is one of the great experiments currently being carried out in medicine," he said.
Dr. Rader observed that CETP is a complex entity, and that a critical question for the field is whether the relationship between CETP inhibition and cardiovascular risk reduction is linear, although hypothetically it is more likely to be curved. Notably, CETP inhibition reached 50%, 70%, and 90% with evacetrapib at daily doses of 30 mg, 100 mg, and 500 mg, respectively.
In addition to determining the optimal degree of CETP inhibition, researchers will also have to identify which patients are most likely to benefit from therapy. The ongoing REVEAL and dal-OUTCOMES trials will provide some insights, but both trials exclude patients with LDL levels greater than 100 mg/dL and "yet it could be argued that subjects with elevated LDL on high-dose statins are the ones most likely to benefit," Dr. Rader said.
Subgroup analyses revealed greater increases in HDL-C with evacetrapib monotherapy among patients who were younger, had lower levels of HDL at baseline and higher triglycerides at baseline, said Dr. Nicholls, clinical director of the Cleveland Clinic Center for Cardiovascular Diagnostics and Prevention.
Greater reductions in LDL cholesterol were observed in those who were younger and had lower levels of HDL cholesterol at baseline.
"This is one of the great experiments currently being carried out in medicine."
The study randomly assigned 398 with elevated LDL or low HDL to receive placebo, evacetrapib monotherapy at daily doses of 30 mg, 100 mg, or 500 mg or statin therapy as described above with or without evacetrapib 100 mg/day for 12 weeks. The mean baseline HDL level was 55 mg/dL and the mean LDL level 144 mg/dL.
No significant increase in adverse events or serious adverse events were observed with evacetrapib monotherapy or in combination with statin therapy on either systolic or diastolic blood pressure, biochemical parameters related to renal, muscle, or liver toxicity. Furthermore, there were no adverse effects on aldosterone or cortisol levels, which have been previously observed with torcetrapib, Dr. Nicholls said.
The study was simultaneously published in the Nov. 16 issue of the Journal of the American Medical Association (JAMA. 2011;306:2099-2109).
The study was sponsored by Eli Lilly. Dr. Nicholls reported consulting for and receiving research support and honoraria from several pharmaceutical companies including Eli Lilly.
ORLANDO – The investigational drug evacetrapib produced dramatic lipid effects with no major safety signals when used as monotherapy or in combination with statin therapy in a phase II randomized trial.
Monotherapy with the cholesteryl ester transfer protein (CETP) inhibitor produced a dose-dependent increase in HDL cholesterol that ranged from 53.6% to 128.8%.
LDL cholesterol levels decreased in a similar fashion from 13.6% to 35.9%, Dr. Stephen J. Nicholls reported at the annual scientific sessions of the American Heart Association.
When evacetrapib, at a dosage of 100 mg, was combined with commonly prescribed statins, LDL cholesterol levels fell significantly, by 46% with simvastatin (Zocor) 40 mg, 48% with atorvastatin (Lipitor), and 52% with rosuvastatin (Crestor) 10 mg. At the same doses, HDL cholesterol levels were increased by 87%, 80%, and 94%, respectively, all highly significant differences.
"This translated to an additional lowering of LDL cholesterol by 32% to 42% in addition to statin therapy," he said.
The data are comparable with those recently achieved by two other CETP inhibitors under investigation, anacetrapib and dalcetrapib. Interestingly, evacetrapib at 500 mg had a similar effect as anacetrapib 100 mg on HDL-C (129% vs. 138%) and LDL-C (136% vs. –40%), but appeared to have a greater impact on triglycerides (–17% vs. –7%), observed Dr. Daniel Rader, who was invited to discuss the paper.
The lack of any major safety signal is encouraging for CETP inhibitors as a class given the early problems surrounding torcetrapib, but that data are still needed from clinical outcome trials to determine whether CETP inhibition can reduce cardiovascular risk, said Dr. Rader, chief of translational medicine and human genetics and director of the preventive cardiovascular program at the University of Pennsylvania, Philadelphia.
"This is one of the great experiments currently being carried out in medicine," he said.
Dr. Rader observed that CETP is a complex entity, and that a critical question for the field is whether the relationship between CETP inhibition and cardiovascular risk reduction is linear, although hypothetically it is more likely to be curved. Notably, CETP inhibition reached 50%, 70%, and 90% with evacetrapib at daily doses of 30 mg, 100 mg, and 500 mg, respectively.
In addition to determining the optimal degree of CETP inhibition, researchers will also have to identify which patients are most likely to benefit from therapy. The ongoing REVEAL and dal-OUTCOMES trials will provide some insights, but both trials exclude patients with LDL levels greater than 100 mg/dL and "yet it could be argued that subjects with elevated LDL on high-dose statins are the ones most likely to benefit," Dr. Rader said.
Subgroup analyses revealed greater increases in HDL-C with evacetrapib monotherapy among patients who were younger, had lower levels of HDL at baseline and higher triglycerides at baseline, said Dr. Nicholls, clinical director of the Cleveland Clinic Center for Cardiovascular Diagnostics and Prevention.
Greater reductions in LDL cholesterol were observed in those who were younger and had lower levels of HDL cholesterol at baseline.
"This is one of the great experiments currently being carried out in medicine."
The study randomly assigned 398 with elevated LDL or low HDL to receive placebo, evacetrapib monotherapy at daily doses of 30 mg, 100 mg, or 500 mg or statin therapy as described above with or without evacetrapib 100 mg/day for 12 weeks. The mean baseline HDL level was 55 mg/dL and the mean LDL level 144 mg/dL.
No significant increase in adverse events or serious adverse events were observed with evacetrapib monotherapy or in combination with statin therapy on either systolic or diastolic blood pressure, biochemical parameters related to renal, muscle, or liver toxicity. Furthermore, there were no adverse effects on aldosterone or cortisol levels, which have been previously observed with torcetrapib, Dr. Nicholls said.
The study was simultaneously published in the Nov. 16 issue of the Journal of the American Medical Association (JAMA. 2011;306:2099-2109).
The study was sponsored by Eli Lilly. Dr. Nicholls reported consulting for and receiving research support and honoraria from several pharmaceutical companies including Eli Lilly.
ORLANDO – The investigational drug evacetrapib produced dramatic lipid effects with no major safety signals when used as monotherapy or in combination with statin therapy in a phase II randomized trial.
Monotherapy with the cholesteryl ester transfer protein (CETP) inhibitor produced a dose-dependent increase in HDL cholesterol that ranged from 53.6% to 128.8%.
LDL cholesterol levels decreased in a similar fashion from 13.6% to 35.9%, Dr. Stephen J. Nicholls reported at the annual scientific sessions of the American Heart Association.
When evacetrapib, at a dosage of 100 mg, was combined with commonly prescribed statins, LDL cholesterol levels fell significantly, by 46% with simvastatin (Zocor) 40 mg, 48% with atorvastatin (Lipitor), and 52% with rosuvastatin (Crestor) 10 mg. At the same doses, HDL cholesterol levels were increased by 87%, 80%, and 94%, respectively, all highly significant differences.
"This translated to an additional lowering of LDL cholesterol by 32% to 42% in addition to statin therapy," he said.
The data are comparable with those recently achieved by two other CETP inhibitors under investigation, anacetrapib and dalcetrapib. Interestingly, evacetrapib at 500 mg had a similar effect as anacetrapib 100 mg on HDL-C (129% vs. 138%) and LDL-C (136% vs. –40%), but appeared to have a greater impact on triglycerides (–17% vs. –7%), observed Dr. Daniel Rader, who was invited to discuss the paper.
The lack of any major safety signal is encouraging for CETP inhibitors as a class given the early problems surrounding torcetrapib, but that data are still needed from clinical outcome trials to determine whether CETP inhibition can reduce cardiovascular risk, said Dr. Rader, chief of translational medicine and human genetics and director of the preventive cardiovascular program at the University of Pennsylvania, Philadelphia.
"This is one of the great experiments currently being carried out in medicine," he said.
Dr. Rader observed that CETP is a complex entity, and that a critical question for the field is whether the relationship between CETP inhibition and cardiovascular risk reduction is linear, although hypothetically it is more likely to be curved. Notably, CETP inhibition reached 50%, 70%, and 90% with evacetrapib at daily doses of 30 mg, 100 mg, and 500 mg, respectively.
In addition to determining the optimal degree of CETP inhibition, researchers will also have to identify which patients are most likely to benefit from therapy. The ongoing REVEAL and dal-OUTCOMES trials will provide some insights, but both trials exclude patients with LDL levels greater than 100 mg/dL and "yet it could be argued that subjects with elevated LDL on high-dose statins are the ones most likely to benefit," Dr. Rader said.
Subgroup analyses revealed greater increases in HDL-C with evacetrapib monotherapy among patients who were younger, had lower levels of HDL at baseline and higher triglycerides at baseline, said Dr. Nicholls, clinical director of the Cleveland Clinic Center for Cardiovascular Diagnostics and Prevention.
Greater reductions in LDL cholesterol were observed in those who were younger and had lower levels of HDL cholesterol at baseline.
"This is one of the great experiments currently being carried out in medicine."
The study randomly assigned 398 with elevated LDL or low HDL to receive placebo, evacetrapib monotherapy at daily doses of 30 mg, 100 mg, or 500 mg or statin therapy as described above with or without evacetrapib 100 mg/day for 12 weeks. The mean baseline HDL level was 55 mg/dL and the mean LDL level 144 mg/dL.
No significant increase in adverse events or serious adverse events were observed with evacetrapib monotherapy or in combination with statin therapy on either systolic or diastolic blood pressure, biochemical parameters related to renal, muscle, or liver toxicity. Furthermore, there were no adverse effects on aldosterone or cortisol levels, which have been previously observed with torcetrapib, Dr. Nicholls said.
The study was simultaneously published in the Nov. 16 issue of the Journal of the American Medical Association (JAMA. 2011;306:2099-2109).
The study was sponsored by Eli Lilly. Dr. Nicholls reported consulting for and receiving research support and honoraria from several pharmaceutical companies including Eli Lilly.
FROM THE ANNUAL SCIENTIFIC SESSIONS OF THE AMERICAN HEART ASSOCIATION
Major Finding: Evacetrapib produced decreases in LDL cholesterol up to 36% and increases in HDL cholesterol up to 129%.
Data Source: Prospective, randomized phase II trial in 398 patients with elevated LDL cholesterol or low HDL cholesterol levels.
Disclosures: The study was sponsored by Eli Lilly. Dr. Nicholls reported consulting for and receiving research support and honoraria from several pharmaceutical companies including Eli Lilly.
Remote Weight-Loss Program Effective Long-Term
ORLANDO – Obese patients coached solely over the phone and Internet lost as much weight as did those counseled in person, according to the findings of a prospective, randomized controlled trial.
Moreover, both groups maintained their weight loss during the 2-year follow-up period of the POWER (Practice-Based Opportunities for Weight Reduction) trial.
At 24 months, 38% of patients in the remote group had lost at least 5% of their initial body weight vs. 41% of the in-person group and just 19% in a control group whose weight-loss was self-directed, Dr. Lawrence J. Appel said at the annual scientific sessions of the American Heart Association.
At 24 months, the mean weight loss was –4.6 kg or 10.1 pounds in the remote group vs. –5.1 kg or 11.2 pounds in the in-person group (P = .63), and –0.8 kg or 1.7 pounds in the control group.
At no point in the study did the weight loss in the two active treatment arms differ, said Dr. Appel, professor of medicine and director of the Welch Center for Prevention, Epidemiology and Clinical Research at Johns Hopkins University in Baltimore.
The sustained weight loss observed in POWER is unprecedented. "It could be considered something of a breakthrough in weight loss," Dr. Frank Sacks, professor of cardiovascular disease prevention at Harvard School of Public Health in Boston, observed at a press briefing. Dr. Sacks was an invited discussant for the paper.
Session moderator Dr. Donald Lloyd-Jones, chair of preventive medicine at Northwestern University, Chicago, called POWER an incredibly important trial given that obesity is by far the No. 1 public health problem in the United States and will drive cardiovascular disease in the coming decades.
"This is absolutely a game changer," he said in an interview. "To see a scalable, very inexpensive therapy, that can be done at arm’s length without too much [intensity] from the provider side, and yet fully engage patients in the process of their weight loss is a very exciting development."
The trial enrolled 415 obese patients with at least one cardiovascular risk factor and a mean weight of 103 kg and mean body mass index of 37 kg/m2.
Patients assigned to the remote group had to enter their weight on the study website before being guided to other educational modules on physical exercise and calorie counting. They could also view their weight-loss goal and progress, Dr. Appel explained.
Physicians reviewed the weight progress reports and played a supportive role through tailored e-mails. Counseling was provided by telephone by employees of Healthways, a disease management promotion company, with no face-to-face contact.
The website and physician’s roles were similar in the in-person group, but these patients received counseling in group meetings, individual meetings, and via telephone from employees of Johns Hopkins.
All patients were encouraged to reduce caloric intake, follow the DASH diet, exercise at least 180 min/week and to log in to the study website at least weekly.
During the first 6 months, the remote group took part in a median of 14 of the 15 recommended phone contacts with their coach and a median of 16 of 18 recommended phone calls over the next 18 months.
The experience in the in-person group was remarkably different, Dr. Appel said. Patients took part in just 6.5 of the 12 recommended group sessions in the first 6 months and only 1 of 18 sessions over the next 18 months, with attendance at individual sessions following a similar pattern. Ultimately, the program "morphed" into a phone intervention, likely because of the convenience and flexibility the format offers, he said. The in-person group maintained 3 of 4 recommended phone contacts with their coaches in the first 6 months and 11 of 12 contacts over the next 18 months.
The study website engaged the patients, with the remote group making 23 of the 26 recommended log ins during the first six months and the in-person group making 20.5 of the 26 log-ins, Dr. Appel said. Over the next 18 months both groups logged in to the website 35 of the 72 recommended times, and visited their primary care provider just once.
During a panel discussion, Dr. Darwin Labarthe, a professor of preventive medicine at Northwestern, said the results are probably the strongest evidence to date on the ability of adults to reduce weight on a sustained basis, but suggested that further follow-up is needed postintervention. He also asked whether the degree of weight loss observed in POWER had an impact on cardiovascular risk factors.
Dr. Appel said the trial was not set up to look at these outcomes, however evidence from other studies suggests that in a prediabetic population, a 5% loss in body weight will reduce the incidence of diabetes by 40%-50%. A reduction in systolic blood pressure also can be expected. Although patients were on medications for this, there was a relationship between systolic blood pressure reduction and weight loss across the entire study population, he said.
At baseline, 76% of patients had hypertension, 68% hypercholesterolemia, 23% diabetes, and 33% metabolic syndrome. Their mean age was 54 years, 64% were women, 56% were white and 41% were black.
The cost of such a remote program depends on how it is rolled out, but that the coaching staff was the biggest driver of expenses at about $600-$800 for the 2 years, Dr. Appel noted. Johns Hopkins is working on implementing the remote intervention and Healthways is expected to make the program commercially available, he said in an interview.
The remote intervention, consisting of phone counseling, an interactive website, and physician support, "has the potential for widespread implementation and should be applicable to the management of other chronic conditions," he told the attendees.
The trial was funded by the National Heart, Lung, and Blood Institute, with data analytic support provided by the National Institute of Diabetes and Digestive and Kidney Disease. Dr. Appel reported no conflicts of interest.
ORLANDO – Obese patients coached solely over the phone and Internet lost as much weight as did those counseled in person, according to the findings of a prospective, randomized controlled trial.
Moreover, both groups maintained their weight loss during the 2-year follow-up period of the POWER (Practice-Based Opportunities for Weight Reduction) trial.
At 24 months, 38% of patients in the remote group had lost at least 5% of their initial body weight vs. 41% of the in-person group and just 19% in a control group whose weight-loss was self-directed, Dr. Lawrence J. Appel said at the annual scientific sessions of the American Heart Association.
At 24 months, the mean weight loss was –4.6 kg or 10.1 pounds in the remote group vs. –5.1 kg or 11.2 pounds in the in-person group (P = .63), and –0.8 kg or 1.7 pounds in the control group.
At no point in the study did the weight loss in the two active treatment arms differ, said Dr. Appel, professor of medicine and director of the Welch Center for Prevention, Epidemiology and Clinical Research at Johns Hopkins University in Baltimore.
The sustained weight loss observed in POWER is unprecedented. "It could be considered something of a breakthrough in weight loss," Dr. Frank Sacks, professor of cardiovascular disease prevention at Harvard School of Public Health in Boston, observed at a press briefing. Dr. Sacks was an invited discussant for the paper.
Session moderator Dr. Donald Lloyd-Jones, chair of preventive medicine at Northwestern University, Chicago, called POWER an incredibly important trial given that obesity is by far the No. 1 public health problem in the United States and will drive cardiovascular disease in the coming decades.
"This is absolutely a game changer," he said in an interview. "To see a scalable, very inexpensive therapy, that can be done at arm’s length without too much [intensity] from the provider side, and yet fully engage patients in the process of their weight loss is a very exciting development."
The trial enrolled 415 obese patients with at least one cardiovascular risk factor and a mean weight of 103 kg and mean body mass index of 37 kg/m2.
Patients assigned to the remote group had to enter their weight on the study website before being guided to other educational modules on physical exercise and calorie counting. They could also view their weight-loss goal and progress, Dr. Appel explained.
Physicians reviewed the weight progress reports and played a supportive role through tailored e-mails. Counseling was provided by telephone by employees of Healthways, a disease management promotion company, with no face-to-face contact.
The website and physician’s roles were similar in the in-person group, but these patients received counseling in group meetings, individual meetings, and via telephone from employees of Johns Hopkins.
All patients were encouraged to reduce caloric intake, follow the DASH diet, exercise at least 180 min/week and to log in to the study website at least weekly.
During the first 6 months, the remote group took part in a median of 14 of the 15 recommended phone contacts with their coach and a median of 16 of 18 recommended phone calls over the next 18 months.
The experience in the in-person group was remarkably different, Dr. Appel said. Patients took part in just 6.5 of the 12 recommended group sessions in the first 6 months and only 1 of 18 sessions over the next 18 months, with attendance at individual sessions following a similar pattern. Ultimately, the program "morphed" into a phone intervention, likely because of the convenience and flexibility the format offers, he said. The in-person group maintained 3 of 4 recommended phone contacts with their coaches in the first 6 months and 11 of 12 contacts over the next 18 months.
The study website engaged the patients, with the remote group making 23 of the 26 recommended log ins during the first six months and the in-person group making 20.5 of the 26 log-ins, Dr. Appel said. Over the next 18 months both groups logged in to the website 35 of the 72 recommended times, and visited their primary care provider just once.
During a panel discussion, Dr. Darwin Labarthe, a professor of preventive medicine at Northwestern, said the results are probably the strongest evidence to date on the ability of adults to reduce weight on a sustained basis, but suggested that further follow-up is needed postintervention. He also asked whether the degree of weight loss observed in POWER had an impact on cardiovascular risk factors.
Dr. Appel said the trial was not set up to look at these outcomes, however evidence from other studies suggests that in a prediabetic population, a 5% loss in body weight will reduce the incidence of diabetes by 40%-50%. A reduction in systolic blood pressure also can be expected. Although patients were on medications for this, there was a relationship between systolic blood pressure reduction and weight loss across the entire study population, he said.
At baseline, 76% of patients had hypertension, 68% hypercholesterolemia, 23% diabetes, and 33% metabolic syndrome. Their mean age was 54 years, 64% were women, 56% were white and 41% were black.
The cost of such a remote program depends on how it is rolled out, but that the coaching staff was the biggest driver of expenses at about $600-$800 for the 2 years, Dr. Appel noted. Johns Hopkins is working on implementing the remote intervention and Healthways is expected to make the program commercially available, he said in an interview.
The remote intervention, consisting of phone counseling, an interactive website, and physician support, "has the potential for widespread implementation and should be applicable to the management of other chronic conditions," he told the attendees.
The trial was funded by the National Heart, Lung, and Blood Institute, with data analytic support provided by the National Institute of Diabetes and Digestive and Kidney Disease. Dr. Appel reported no conflicts of interest.
ORLANDO – Obese patients coached solely over the phone and Internet lost as much weight as did those counseled in person, according to the findings of a prospective, randomized controlled trial.
Moreover, both groups maintained their weight loss during the 2-year follow-up period of the POWER (Practice-Based Opportunities for Weight Reduction) trial.
At 24 months, 38% of patients in the remote group had lost at least 5% of their initial body weight vs. 41% of the in-person group and just 19% in a control group whose weight-loss was self-directed, Dr. Lawrence J. Appel said at the annual scientific sessions of the American Heart Association.
At 24 months, the mean weight loss was –4.6 kg or 10.1 pounds in the remote group vs. –5.1 kg or 11.2 pounds in the in-person group (P = .63), and –0.8 kg or 1.7 pounds in the control group.
At no point in the study did the weight loss in the two active treatment arms differ, said Dr. Appel, professor of medicine and director of the Welch Center for Prevention, Epidemiology and Clinical Research at Johns Hopkins University in Baltimore.
The sustained weight loss observed in POWER is unprecedented. "It could be considered something of a breakthrough in weight loss," Dr. Frank Sacks, professor of cardiovascular disease prevention at Harvard School of Public Health in Boston, observed at a press briefing. Dr. Sacks was an invited discussant for the paper.
Session moderator Dr. Donald Lloyd-Jones, chair of preventive medicine at Northwestern University, Chicago, called POWER an incredibly important trial given that obesity is by far the No. 1 public health problem in the United States and will drive cardiovascular disease in the coming decades.
"This is absolutely a game changer," he said in an interview. "To see a scalable, very inexpensive therapy, that can be done at arm’s length without too much [intensity] from the provider side, and yet fully engage patients in the process of their weight loss is a very exciting development."
The trial enrolled 415 obese patients with at least one cardiovascular risk factor and a mean weight of 103 kg and mean body mass index of 37 kg/m2.
Patients assigned to the remote group had to enter their weight on the study website before being guided to other educational modules on physical exercise and calorie counting. They could also view their weight-loss goal and progress, Dr. Appel explained.
Physicians reviewed the weight progress reports and played a supportive role through tailored e-mails. Counseling was provided by telephone by employees of Healthways, a disease management promotion company, with no face-to-face contact.
The website and physician’s roles were similar in the in-person group, but these patients received counseling in group meetings, individual meetings, and via telephone from employees of Johns Hopkins.
All patients were encouraged to reduce caloric intake, follow the DASH diet, exercise at least 180 min/week and to log in to the study website at least weekly.
During the first 6 months, the remote group took part in a median of 14 of the 15 recommended phone contacts with their coach and a median of 16 of 18 recommended phone calls over the next 18 months.
The experience in the in-person group was remarkably different, Dr. Appel said. Patients took part in just 6.5 of the 12 recommended group sessions in the first 6 months and only 1 of 18 sessions over the next 18 months, with attendance at individual sessions following a similar pattern. Ultimately, the program "morphed" into a phone intervention, likely because of the convenience and flexibility the format offers, he said. The in-person group maintained 3 of 4 recommended phone contacts with their coaches in the first 6 months and 11 of 12 contacts over the next 18 months.
The study website engaged the patients, with the remote group making 23 of the 26 recommended log ins during the first six months and the in-person group making 20.5 of the 26 log-ins, Dr. Appel said. Over the next 18 months both groups logged in to the website 35 of the 72 recommended times, and visited their primary care provider just once.
During a panel discussion, Dr. Darwin Labarthe, a professor of preventive medicine at Northwestern, said the results are probably the strongest evidence to date on the ability of adults to reduce weight on a sustained basis, but suggested that further follow-up is needed postintervention. He also asked whether the degree of weight loss observed in POWER had an impact on cardiovascular risk factors.
Dr. Appel said the trial was not set up to look at these outcomes, however evidence from other studies suggests that in a prediabetic population, a 5% loss in body weight will reduce the incidence of diabetes by 40%-50%. A reduction in systolic blood pressure also can be expected. Although patients were on medications for this, there was a relationship between systolic blood pressure reduction and weight loss across the entire study population, he said.
At baseline, 76% of patients had hypertension, 68% hypercholesterolemia, 23% diabetes, and 33% metabolic syndrome. Their mean age was 54 years, 64% were women, 56% were white and 41% were black.
The cost of such a remote program depends on how it is rolled out, but that the coaching staff was the biggest driver of expenses at about $600-$800 for the 2 years, Dr. Appel noted. Johns Hopkins is working on implementing the remote intervention and Healthways is expected to make the program commercially available, he said in an interview.
The remote intervention, consisting of phone counseling, an interactive website, and physician support, "has the potential for widespread implementation and should be applicable to the management of other chronic conditions," he told the attendees.
The trial was funded by the National Heart, Lung, and Blood Institute, with data analytic support provided by the National Institute of Diabetes and Digestive and Kidney Disease. Dr. Appel reported no conflicts of interest.
FROM THE ANNUAL SCIENTIFIC SESSIONS OF THE AMERICAN HEART ASSOCIATION
Major Finding: At 24 months, the mean weight loss was –4.6 kg or 10.1 pounds in the remote group vs. –5.1 kg or 11.2 pounds in the in-person group (P = .63), and –0.8 kg or 1.7 pounds in the control group.
Data Source: A 2-year prospective, randomized controlled trial.
Disclosures: The trial was funded by the National Heart, Lung, and Blood Institute, with data analytic support also provided by the National Institute of Diabetes and Digestive and Kidney Disease. Dr. Appel reported no conflicts of interest.