Caroline Helwick

NEW ORLEANS  Select patients with unprotected left main coronary artery stenosis can be effectively treated with percutaneous coronary intervention with sirolimus-eluting stents rather than coronary artery bypass grafting, South Korean investigators reported at a late-breaking clinical trials session of the annual meeting of the American College of Cardiology.

PCI with sirolimus-eluting stents appears to be an alternative to coronary artery bypass grafting based on a noninferior incidence of major cardiac and cerebrovascular events in a median 2-year follow-up of 600 patients with unprotected left main coronary artery stenosis randomized to undergo either CABG or PCI with a sirolimus-eluting stent [Cordis, Johnson & Johnson], said Dr. Seung-Jung Park, the principal investigator of PRECOMBAT (Premier of Randomized Comparison of Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease). 

Major adverse cardiac or cerebrovascular events (MACCE) included all-cause death, myocardial infarction, stroke, ischemia-driven target-vessel revascularization, and cerebrovascular events, said Dr. Park of Asan Medical Center, Seoul, South Korea. 

The rate of MACCE at 2 years was comparable at 12.2% for PCI-treated patients and 8.1% for CABG-treated patients. The composite of death, myocardial infarction and stroke  which the investigators considered a marker of safety  was 4.4% in the PCI group and 4.7% in the CABG group. The major difference was the rate of ischemia-driven target-vessel revascularization ? 9% with PCI and 4.2% with CABG. Further, in subgroup analyses, PCI was associated with a higher risk of MACCE in patients with unprotected left main coronary artery stenosis plus three-vessel disease.

Concomitant with the presentation, the results were published online in the New England Journal of Medicine (N. Engl. J. Med. 2011, April 4 [doi: 10.1056/NEJMoa1100452]). 

PRECOMBAT baseline patient characteristics were similar. Mean age was 62 years, 76.5% were men, mean ejection fraction was 60% and high operative risk was noted for 6% of the PCI group and 8% of the CABG group. Median follow-up was 24 months.

The primary end point was a composite comparison of MACCE at 1 year and 2 years. The primary analysis was a noninferiority comparison. 

MACCE occurred in 26 patients assigned to PCI and in 20 patients assigned to CABG, for cumulative event rates of 8.7% and 6.7%, respectively. The 2.0% absolute risk difference supported noninferiority of PCI to CABG (P = .01). When patient analysis was based on the actual treatment received, however, the 1-year cumulative MACCE rates were 9.2% for PCI and 5.9%, for CABG (P = .04 for noninferiority).

The all-cause death rate in year 1 was 2% for PCI and 2.7% for CABG and in year 2 was 2.4% and 3.4%, respectively (P = .45). Cardiac deaths occurred in 1.0% and 2.7%, respectively, at 2 years.

Strokes and myocardial infarction were also infrequent and the rate of these events did not differ between the treatment arms. Symptomatic graft occlusion and stent thrombosis were observed in 0.3% of the PCI group and in 1.4% of the CABG group. There were no differences by subgroup.

Describing the procedural characteristics, Dr. Park noted that in the PCI group the mean number of stents per patient was 2.7 and in the CABG group the mean number of grafts was 2.7. The procedures were completed in 205 PCI patients and in 211 CABG patients, for comparable revascularization rates of 68% and 70%, respectively.

"Our major finding, that event rates after PCI and CABG did not differ signifi?cantly in this clinical setting, are in agreement with the results of the SYN?TAX substudy involving patients with left main coronary artery stenosis," he said.

In SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery), CABG showed more benefit than did PCI for the overall study population (N. Engl. J. Med. 2009;360:961-72). 

Among patients with left main coronary artery disease in SYNTAX, however, the 12-month rate of MACCE was similar at 13.7% in the CABG group and 15.8% in the PCI group (P = .44). The rate of repeat revascularization among patients with left main coronary artery disease was 11.8% in the PCI group and 6.5% in the CABG group (P = .02), but the CABG group had 2.7% rate of stroke as compared to a 0.3% rate in the PCI subgroup; (P = .01). 

In SYNTAX, nearly 37% of patients with left main coronary artery disease also had three-vessel disease. The subgroup with concomitant two- or three-vessel disease had higher MACCE rates than did the subgroups of patients with left main coronary artery disease alone or in combination with one-vessel disease.

Event rates at 1 year in SYNTAX were higher than those in PRECOMBAT, and the PRECOMBAT patient population had less complex disease, lower SYNTAX scores, and less comorbidity, Dr. Park said.

Dr. Park reported receiving consulting fees and honoraria from Johnson & Johnson and Cordis. 

NEW ORLEANS  Select patients with unprotected left main coronary artery stenosis can be effectively treated with percutaneous coronary intervention with sirolimus-eluting stents rather than coronary artery bypass grafting, South Korean investigators reported at a late-breaking clinical trials session of the annual meeting of the American College of Cardiology.

PCI with sirolimus-eluting stents appears to be an alternative to coronary artery bypass grafting based on a noninferior incidence of major cardiac and cerebrovascular events in a median 2-year follow-up of 600 patients with unprotected left main coronary artery stenosis randomized to undergo either CABG or PCI with a sirolimus-eluting stent [Cordis, Johnson & Johnson], said Dr. Seung-Jung Park, the principal investigator of PRECOMBAT (Premier of Randomized Comparison of Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease). 

Major adverse cardiac or cerebrovascular events (MACCE) included all-cause death, myocardial infarction, stroke, ischemia-driven target-vessel revascularization, and cerebrovascular events, said Dr. Park of Asan Medical Center, Seoul, South Korea. 

The rate of MACCE at 2 years was comparable at 12.2% for PCI-treated patients and 8.1% for CABG-treated patients. The composite of death, myocardial infarction and stroke  which the investigators considered a marker of safety  was 4.4% in the PCI group and 4.7% in the CABG group. The major difference was the rate of ischemia-driven target-vessel revascularization ? 9% with PCI and 4.2% with CABG. Further, in subgroup analyses, PCI was associated with a higher risk of MACCE in patients with unprotected left main coronary artery stenosis plus three-vessel disease.

Concomitant with the presentation, the results were published online in the New England Journal of Medicine (N. Engl. J. Med. 2011, April 4 [doi: 10.1056/NEJMoa1100452]). 

PRECOMBAT baseline patient characteristics were similar. Mean age was 62 years, 76.5% were men, mean ejection fraction was 60% and high operative risk was noted for 6% of the PCI group and 8% of the CABG group. Median follow-up was 24 months.

The primary end point was a composite comparison of MACCE at 1 year and 2 years. The primary analysis was a noninferiority comparison. 

MACCE occurred in 26 patients assigned to PCI and in 20 patients assigned to CABG, for cumulative event rates of 8.7% and 6.7%, respectively. The 2.0% absolute risk difference supported noninferiority of PCI to CABG (P = .01). When patient analysis was based on the actual treatment received, however, the 1-year cumulative MACCE rates were 9.2% for PCI and 5.9%, for CABG (P = .04 for noninferiority).

The all-cause death rate in year 1 was 2% for PCI and 2.7% for CABG and in year 2 was 2.4% and 3.4%, respectively (P = .45). Cardiac deaths occurred in 1.0% and 2.7%, respectively, at 2 years.

Strokes and myocardial infarction were also infrequent and the rate of these events did not differ between the treatment arms. Symptomatic graft occlusion and stent thrombosis were observed in 0.3% of the PCI group and in 1.4% of the CABG group. There were no differences by subgroup.

Describing the procedural characteristics, Dr. Park noted that in the PCI group the mean number of stents per patient was 2.7 and in the CABG group the mean number of grafts was 2.7. The procedures were completed in 205 PCI patients and in 211 CABG patients, for comparable revascularization rates of 68% and 70%, respectively.

"Our major finding, that event rates after PCI and CABG did not differ signifi?cantly in this clinical setting, are in agreement with the results of the SYN?TAX substudy involving patients with left main coronary artery stenosis," he said.

In SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery), CABG showed more benefit than did PCI for the overall study population (N. Engl. J. Med. 2009;360:961-72). 

Among patients with left main coronary artery disease in SYNTAX, however, the 12-month rate of MACCE was similar at 13.7% in the CABG group and 15.8% in the PCI group (P = .44). The rate of repeat revascularization among patients with left main coronary artery disease was 11.8% in the PCI group and 6.5% in the CABG group (P = .02), but the CABG group had 2.7% rate of stroke as compared to a 0.3% rate in the PCI subgroup; (P = .01). 

In SYNTAX, nearly 37% of patients with left main coronary artery disease also had three-vessel disease. The subgroup with concomitant two- or three-vessel disease had higher MACCE rates than did the subgroups of patients with left main coronary artery disease alone or in combination with one-vessel disease.

Event rates at 1 year in SYNTAX were higher than those in PRECOMBAT, and the PRECOMBAT patient population had less complex disease, lower SYNTAX scores, and less comorbidity, Dr. Park said.

Dr. Park reported receiving consulting fees and honoraria from Johnson & Johnson and Cordis. 

NEW ORLEANS  Select patients with unprotected left main coronary artery stenosis can be effectively treated with percutaneous coronary intervention with sirolimus-eluting stents rather than coronary artery bypass grafting, South Korean investigators reported at a late-breaking clinical trials session of the annual meeting of the American College of Cardiology.

PCI with sirolimus-eluting stents appears to be an alternative to coronary artery bypass grafting based on a noninferior incidence of major cardiac and cerebrovascular events in a median 2-year follow-up of 600 patients with unprotected left main coronary artery stenosis randomized to undergo either CABG or PCI with a sirolimus-eluting stent [Cordis, Johnson & Johnson], said Dr. Seung-Jung Park, the principal investigator of PRECOMBAT (Premier of Randomized Comparison of Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease). 

Major adverse cardiac or cerebrovascular events (MACCE) included all-cause death, myocardial infarction, stroke, ischemia-driven target-vessel revascularization, and cerebrovascular events, said Dr. Park of Asan Medical Center, Seoul, South Korea. 

The rate of MACCE at 2 years was comparable at 12.2% for PCI-treated patients and 8.1% for CABG-treated patients. The composite of death, myocardial infarction and stroke  which the investigators considered a marker of safety  was 4.4% in the PCI group and 4.7% in the CABG group. The major difference was the rate of ischemia-driven target-vessel revascularization ? 9% with PCI and 4.2% with CABG. Further, in subgroup analyses, PCI was associated with a higher risk of MACCE in patients with unprotected left main coronary artery stenosis plus three-vessel disease.

Concomitant with the presentation, the results were published online in the New England Journal of Medicine (N. Engl. J. Med. 2011, April 4 [doi: 10.1056/NEJMoa1100452]). 

PRECOMBAT baseline patient characteristics were similar. Mean age was 62 years, 76.5% were men, mean ejection fraction was 60% and high operative risk was noted for 6% of the PCI group and 8% of the CABG group. Median follow-up was 24 months.

The primary end point was a composite comparison of MACCE at 1 year and 2 years. The primary analysis was a noninferiority comparison. 

MACCE occurred in 26 patients assigned to PCI and in 20 patients assigned to CABG, for cumulative event rates of 8.7% and 6.7%, respectively. The 2.0% absolute risk difference supported noninferiority of PCI to CABG (P = .01). When patient analysis was based on the actual treatment received, however, the 1-year cumulative MACCE rates were 9.2% for PCI and 5.9%, for CABG (P = .04 for noninferiority).

The all-cause death rate in year 1 was 2% for PCI and 2.7% for CABG and in year 2 was 2.4% and 3.4%, respectively (P = .45). Cardiac deaths occurred in 1.0% and 2.7%, respectively, at 2 years.

Strokes and myocardial infarction were also infrequent and the rate of these events did not differ between the treatment arms. Symptomatic graft occlusion and stent thrombosis were observed in 0.3% of the PCI group and in 1.4% of the CABG group. There were no differences by subgroup.

Describing the procedural characteristics, Dr. Park noted that in the PCI group the mean number of stents per patient was 2.7 and in the CABG group the mean number of grafts was 2.7. The procedures were completed in 205 PCI patients and in 211 CABG patients, for comparable revascularization rates of 68% and 70%, respectively.

"Our major finding, that event rates after PCI and CABG did not differ signifi?cantly in this clinical setting, are in agreement with the results of the SYN?TAX substudy involving patients with left main coronary artery stenosis," he said.

In SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery), CABG showed more benefit than did PCI for the overall study population (N. Engl. J. Med. 2009;360:961-72). 

Among patients with left main coronary artery disease in SYNTAX, however, the 12-month rate of MACCE was similar at 13.7% in the CABG group and 15.8% in the PCI group (P = .44). The rate of repeat revascularization among patients with left main coronary artery disease was 11.8% in the PCI group and 6.5% in the CABG group (P = .02), but the CABG group had 2.7% rate of stroke as compared to a 0.3% rate in the PCI subgroup; (P = .01). 

In SYNTAX, nearly 37% of patients with left main coronary artery disease also had three-vessel disease. The subgroup with concomitant two- or three-vessel disease had higher MACCE rates than did the subgroups of patients with left main coronary artery disease alone or in combination with one-vessel disease.

Event rates at 1 year in SYNTAX were higher than those in PRECOMBAT, and the PRECOMBAT patient population had less complex disease, lower SYNTAX scores, and less comorbidity, Dr. Park said.

Dr. Park reported receiving consulting fees and honoraria from Johnson & Johnson and Cordis. 

Major Finding: During the open-label phase of randomized trials studied, the lower mortality among those who initially received active therapy persisted (odds ratio, 0.90; P = .0035), as did the reduction in cardiovascular mortality (OR, 0.82; P = .0014).

Data Source: A meta-analysis involving 44,255 patients in eight clinical trials of lipid-lowering therapy. All trials involved an open-label phase after the randomized treatment period ended.

Disclosures: Dr. Kostis and Dr. Moriarty reported having no relevant conflicts of interest.

NEW ORLEANS – In major clinical trials of lipid-lowering agents, the mortality benefit derived from medical therapy persists long after the studies end, according to a meta-analysis presented at the annual meeting of the American College of Cardiology.

Furthermore, placebo recipients who cross over to lipid-lowering therapy in the open-label phases of the studies demonstrate survival benefits as well, but never attain the protection achieved by being randomized to active treatment earlier on, according to Dr. William J. Kostis of Massachusetts General Hospital, Boston. “Persons with risk factors for coronary artery disease should be treated early,” Dr. Kostis said in an interview. “The sooner you treat, the better.”

He and his colleagues searched several major databases to identify randomized trials of lipid-lowering therapies that also contained an analysis of patient outcomes after the randomized portion of the trials had ended and an open-label phase had begun. Active treatment in the trials involved statins, niacin, cholestyramine, or gemfibrozil.

The analysis included eight clinical trials involving 44,255 patients, of whom 8,144 died during follow-up.

The average patient remained on the assigned treatment for approximately 5 years and was on the lipid-lowering agent in the open-label phase for approximately 6 years.

During the randomized phase of the trials, the mean all-cause mortality was significantly lower for the active treatment group (odds ratio, 0.84), as was cardiovascular mortality (OR, 0.72). The lower mortality among those initially receiving active therapy persisted during the open-label follow-up phase (OR, 0.90), as did the reduction in cardiovascular mortality (OR, 0.82).

“Being treated with a beneficial medication for a longer period of time is better, possibly because we are arresting pathophysiology at an earlier stage,” Dr. Kostis proposed. He added that statins may be reducing the size of infarcts in patients who have myocardial infarctions.

Dr. Patrick Moriarty, a lipid specialist and professor of medicine at the University of Kansas in Kansas City, agreed. “We need to start lipid-lowering therapy early to get the most benefit,” and this includes interventions in children when necessary, he added.

“We treat pediatric patients all the time,” Dr. Moriarty said, “not only those with familial hyperlipidemias but also those with metabolic syndrome. … The future emphasis will be, 'the sooner the better.'”

Major Finding: During the open-label phase of randomized trials studied, the lower mortality among those who initially received active therapy persisted (odds ratio, 0.90; P = .0035), as did the reduction in cardiovascular mortality (OR, 0.82; P = .0014).

Data Source: A meta-analysis involving 44,255 patients in eight clinical trials of lipid-lowering therapy. All trials involved an open-label phase after the randomized treatment period ended.

Disclosures: Dr. Kostis and Dr. Moriarty reported having no relevant conflicts of interest.

NEW ORLEANS – In major clinical trials of lipid-lowering agents, the mortality benefit derived from medical therapy persists long after the studies end, according to a meta-analysis presented at the annual meeting of the American College of Cardiology.

Furthermore, placebo recipients who cross over to lipid-lowering therapy in the open-label phases of the studies demonstrate survival benefits as well, but never attain the protection achieved by being randomized to active treatment earlier on, according to Dr. William J. Kostis of Massachusetts General Hospital, Boston. “Persons with risk factors for coronary artery disease should be treated early,” Dr. Kostis said in an interview. “The sooner you treat, the better.”

He and his colleagues searched several major databases to identify randomized trials of lipid-lowering therapies that also contained an analysis of patient outcomes after the randomized portion of the trials had ended and an open-label phase had begun. Active treatment in the trials involved statins, niacin, cholestyramine, or gemfibrozil.

The analysis included eight clinical trials involving 44,255 patients, of whom 8,144 died during follow-up.

The average patient remained on the assigned treatment for approximately 5 years and was on the lipid-lowering agent in the open-label phase for approximately 6 years.

During the randomized phase of the trials, the mean all-cause mortality was significantly lower for the active treatment group (odds ratio, 0.84), as was cardiovascular mortality (OR, 0.72). The lower mortality among those initially receiving active therapy persisted during the open-label follow-up phase (OR, 0.90), as did the reduction in cardiovascular mortality (OR, 0.82).

“Being treated with a beneficial medication for a longer period of time is better, possibly because we are arresting pathophysiology at an earlier stage,” Dr. Kostis proposed. He added that statins may be reducing the size of infarcts in patients who have myocardial infarctions.

Dr. Patrick Moriarty, a lipid specialist and professor of medicine at the University of Kansas in Kansas City, agreed. “We need to start lipid-lowering therapy early to get the most benefit,” and this includes interventions in children when necessary, he added.

“We treat pediatric patients all the time,” Dr. Moriarty said, “not only those with familial hyperlipidemias but also those with metabolic syndrome. … The future emphasis will be, 'the sooner the better.'”

Major Finding: During the open-label phase of randomized trials studied, the lower mortality among those who initially received active therapy persisted (odds ratio, 0.90; P = .0035), as did the reduction in cardiovascular mortality (OR, 0.82; P = .0014).

Data Source: A meta-analysis involving 44,255 patients in eight clinical trials of lipid-lowering therapy. All trials involved an open-label phase after the randomized treatment period ended.

Disclosures: Dr. Kostis and Dr. Moriarty reported having no relevant conflicts of interest.

NEW ORLEANS – In major clinical trials of lipid-lowering agents, the mortality benefit derived from medical therapy persists long after the studies end, according to a meta-analysis presented at the annual meeting of the American College of Cardiology.

Furthermore, placebo recipients who cross over to lipid-lowering therapy in the open-label phases of the studies demonstrate survival benefits as well, but never attain the protection achieved by being randomized to active treatment earlier on, according to Dr. William J. Kostis of Massachusetts General Hospital, Boston. “Persons with risk factors for coronary artery disease should be treated early,” Dr. Kostis said in an interview. “The sooner you treat, the better.”

He and his colleagues searched several major databases to identify randomized trials of lipid-lowering therapies that also contained an analysis of patient outcomes after the randomized portion of the trials had ended and an open-label phase had begun. Active treatment in the trials involved statins, niacin, cholestyramine, or gemfibrozil.

The analysis included eight clinical trials involving 44,255 patients, of whom 8,144 died during follow-up.

The average patient remained on the assigned treatment for approximately 5 years and was on the lipid-lowering agent in the open-label phase for approximately 6 years.

During the randomized phase of the trials, the mean all-cause mortality was significantly lower for the active treatment group (odds ratio, 0.84), as was cardiovascular mortality (OR, 0.72). The lower mortality among those initially receiving active therapy persisted during the open-label follow-up phase (OR, 0.90), as did the reduction in cardiovascular mortality (OR, 0.82).

“Being treated with a beneficial medication for a longer period of time is better, possibly because we are arresting pathophysiology at an earlier stage,” Dr. Kostis proposed. He added that statins may be reducing the size of infarcts in patients who have myocardial infarctions.

Dr. Patrick Moriarty, a lipid specialist and professor of medicine at the University of Kansas in Kansas City, agreed. “We need to start lipid-lowering therapy early to get the most benefit,” and this includes interventions in children when necessary, he added.

“We treat pediatric patients all the time,” Dr. Moriarty said, “not only those with familial hyperlipidemias but also those with metabolic syndrome. … The future emphasis will be, 'the sooner the better.'”

Major Finding: LDL-C levels of less than 100 mg/dL were achieved by 76% of mipomersen-treated patients and 38% of placebo-treated patients. LDL-C levels of less than 70 mg/dL were achieved by 50% and 8%, respectively.

Data Source: The double-blind study included 158 high-risk patients who were unable to achieve target LDL-C levels on optimal therapy and were randomized 2:1 to 200 mg subcutaneous mipomersen or placebo weekly.

Disclosures: The study was sponsored by Isis Pharmaceuticals and Genzyme Corporation. Dr. Cromwell has received consultant fees or honoraria from Isis. Dr. Moriarty has participated in clinical trials of mipomersen.

NEW ORLEANS – In patients with hypercholesterolemia and high cardiovascular risk, the novel agent mipomersen administered as add-on therapy led to robust reductions in LDL cholesterol, based on the results of a double-blind, phase III study.

“In high-risk patients refractory to maximally tolerated statin therapy, the addition of mipomersen significantly reduced LDL-C and other atherogenic lipids and lipoproteins,” said Dr. William C. Cromwell of the Presbyterian Cardiovascular Institute in Charlotte, N.C.

Mipomersen is the first of a new class of agents called apolipoprotein B (apoB) synthesis inhibitors. In the study, the drug was administered subcutaneously once a week. Among its side effects were injection site reactions, increases in alanine aminotransferase (ALT) levels, and steatosis.

The study included 158 patients at high risk for cardiovascular events who were unable to achieve target LDL-C levels with statins, bile-acid sequestrants, and niacin. At baseline, all patients were on maximally tolerated doses of a statin; 63 were on the maximal approved dose, and 25 were also receiving ezetimibe.

All subjects had LDL-C levels of at least 100 mg/dL and triglycerides below 200 mg/dL. They were randomized 2:1 to 200 mg mipomersen or placebo weekly for 26 weeks. The primary end point was percent change in LDL-C from baseline at week 28 or 2 weeks after the last dose if treatment was not completed.

LDL-C levels of less than 100 mg/dL were achieved by 77 (76%) mipomersen-treated patients, compared with 19 (38%) placebo-treated patients. LDL-C levels of less than 70 mg/dL were achieved by 51 (50%) and 4 (8%), respectively.

The percent reduction in LDL cholesterol from baseline to the primary efficacy time point was a 37% drop in the mipomersen arm and a 5% drop in the placebo arm, a significant difference.

“LDL-C levels decreased through the first 17 weeks of treatment and remained relatively low through week 28,” Dr. Cromwell observed. “Mipomersen's lipid-lowering effects were independent of baseline LDL-C or race, and were similar for patients with and without diabetes.”

The effect of the drug in the diabetic subset was robust. In the diabetes cohort, the mean decline in LDL-C from baseline was 51% for the 56 patients on mipomersen and 32% for the 29 on placebo.

Mipomersen also was associated with significant reductions from baseline values in apoB (38%), total cholesterol (26%), non-HDL cholesterol (36%), and lipoprotein(a) (24%). HDL-C levels did not change significantly from baseline.

Sixty of the 105 mipomersen-treated patients (57%) and 44 of 52 placebo patients (85%) completed treatment. A total of 26 mipomersen-treated patients and 2 placebo-treated patients discontinued as a result of on-treatment adverse events. Of the mipomersen noncompleters, seven discontinued because of a liver enzyme-related adverse event, and seven stopped because of an injection site reaction.

Injection site reactions were the most common adverse event, occurring in 78% of the mipomersen group and 31% of the placebo group. Flu-like symptoms occurred in 34% and 21%, respectively. “Injection site reaction is the biggest side effect with this drug. This ranges from induration to redness, and some patients have skin discoloration,” Dr. Cromwell acknowledged.

ALT elevations at least 3 times the upper limit of normal were observed in 14% of patients on mipomersen, versus none receiving placebo, but this occurred without concomitant significant bilirubin elevations, he said. For 10% of patients, ALT elevations occurred on consecutive measurements at least 7 days apart.

Approximately one-third of patients had an increase in steatosis, defined as liver fat increasing by at least 5%; median percent change from baseline was 15%. “This does not represent a huge accumulation of fat. Instead, it is a signal that it's there at 28 weeks, and it is not particularly worrying. In a series of patients with much longer exposures, there is a plateau in this increase.”

Dr. Patrick Moriarty, a lipid specialist and professor of medicine at the University of Kansas, Kansas City, commented, “We treat many refractory patients, and I can tell you that a drug of this class is very much needed in this patient population. It will help get their lipid numbers down.”

The fact that patients achieve good LDL-C reductions on top of statin therapy is very encouraging, he said, noting, “The drug is not for every patient, but it could fill the need for an effective treatment in a small subset.”

Dr. Moriarty said the injectable delivery will not be a barrier to acceptance. “Patients can do these injections themselves, just like diabetes patients do. In studies I've participated in, we offer patients the opportunity to have the nurse give them the injections but most patients learn to do [the injections] themselves.”

Major Finding: LDL-C levels of less than 100 mg/dL were achieved by 76% of mipomersen-treated patients and 38% of placebo-treated patients. LDL-C levels of less than 70 mg/dL were achieved by 50% and 8%, respectively.

Data Source: The double-blind study included 158 high-risk patients who were unable to achieve target LDL-C levels on optimal therapy and were randomized 2:1 to 200 mg subcutaneous mipomersen or placebo weekly.

Disclosures: The study was sponsored by Isis Pharmaceuticals and Genzyme Corporation. Dr. Cromwell has received consultant fees or honoraria from Isis. Dr. Moriarty has participated in clinical trials of mipomersen.

NEW ORLEANS – In patients with hypercholesterolemia and high cardiovascular risk, the novel agent mipomersen administered as add-on therapy led to robust reductions in LDL cholesterol, based on the results of a double-blind, phase III study.

“In high-risk patients refractory to maximally tolerated statin therapy, the addition of mipomersen significantly reduced LDL-C and other atherogenic lipids and lipoproteins,” said Dr. William C. Cromwell of the Presbyterian Cardiovascular Institute in Charlotte, N.C.

Mipomersen is the first of a new class of agents called apolipoprotein B (apoB) synthesis inhibitors. In the study, the drug was administered subcutaneously once a week. Among its side effects were injection site reactions, increases in alanine aminotransferase (ALT) levels, and steatosis.

The study included 158 patients at high risk for cardiovascular events who were unable to achieve target LDL-C levels with statins, bile-acid sequestrants, and niacin. At baseline, all patients were on maximally tolerated doses of a statin; 63 were on the maximal approved dose, and 25 were also receiving ezetimibe.

All subjects had LDL-C levels of at least 100 mg/dL and triglycerides below 200 mg/dL. They were randomized 2:1 to 200 mg mipomersen or placebo weekly for 26 weeks. The primary end point was percent change in LDL-C from baseline at week 28 or 2 weeks after the last dose if treatment was not completed.

LDL-C levels of less than 100 mg/dL were achieved by 77 (76%) mipomersen-treated patients, compared with 19 (38%) placebo-treated patients. LDL-C levels of less than 70 mg/dL were achieved by 51 (50%) and 4 (8%), respectively.

The percent reduction in LDL cholesterol from baseline to the primary efficacy time point was a 37% drop in the mipomersen arm and a 5% drop in the placebo arm, a significant difference.

“LDL-C levels decreased through the first 17 weeks of treatment and remained relatively low through week 28,” Dr. Cromwell observed. “Mipomersen's lipid-lowering effects were independent of baseline LDL-C or race, and were similar for patients with and without diabetes.”

The effect of the drug in the diabetic subset was robust. In the diabetes cohort, the mean decline in LDL-C from baseline was 51% for the 56 patients on mipomersen and 32% for the 29 on placebo.

Mipomersen also was associated with significant reductions from baseline values in apoB (38%), total cholesterol (26%), non-HDL cholesterol (36%), and lipoprotein(a) (24%). HDL-C levels did not change significantly from baseline.

Sixty of the 105 mipomersen-treated patients (57%) and 44 of 52 placebo patients (85%) completed treatment. A total of 26 mipomersen-treated patients and 2 placebo-treated patients discontinued as a result of on-treatment adverse events. Of the mipomersen noncompleters, seven discontinued because of a liver enzyme-related adverse event, and seven stopped because of an injection site reaction.

Injection site reactions were the most common adverse event, occurring in 78% of the mipomersen group and 31% of the placebo group. Flu-like symptoms occurred in 34% and 21%, respectively. “Injection site reaction is the biggest side effect with this drug. This ranges from induration to redness, and some patients have skin discoloration,” Dr. Cromwell acknowledged.

ALT elevations at least 3 times the upper limit of normal were observed in 14% of patients on mipomersen, versus none receiving placebo, but this occurred without concomitant significant bilirubin elevations, he said. For 10% of patients, ALT elevations occurred on consecutive measurements at least 7 days apart.

Approximately one-third of patients had an increase in steatosis, defined as liver fat increasing by at least 5%; median percent change from baseline was 15%. “This does not represent a huge accumulation of fat. Instead, it is a signal that it's there at 28 weeks, and it is not particularly worrying. In a series of patients with much longer exposures, there is a plateau in this increase.”

Dr. Patrick Moriarty, a lipid specialist and professor of medicine at the University of Kansas, Kansas City, commented, “We treat many refractory patients, and I can tell you that a drug of this class is very much needed in this patient population. It will help get their lipid numbers down.”

The fact that patients achieve good LDL-C reductions on top of statin therapy is very encouraging, he said, noting, “The drug is not for every patient, but it could fill the need for an effective treatment in a small subset.”

Dr. Moriarty said the injectable delivery will not be a barrier to acceptance. “Patients can do these injections themselves, just like diabetes patients do. In studies I've participated in, we offer patients the opportunity to have the nurse give them the injections but most patients learn to do [the injections] themselves.”

Major Finding: LDL-C levels of less than 100 mg/dL were achieved by 76% of mipomersen-treated patients and 38% of placebo-treated patients. LDL-C levels of less than 70 mg/dL were achieved by 50% and 8%, respectively.

Data Source: The double-blind study included 158 high-risk patients who were unable to achieve target LDL-C levels on optimal therapy and were randomized 2:1 to 200 mg subcutaneous mipomersen or placebo weekly.

Disclosures: The study was sponsored by Isis Pharmaceuticals and Genzyme Corporation. Dr. Cromwell has received consultant fees or honoraria from Isis. Dr. Moriarty has participated in clinical trials of mipomersen.

NEW ORLEANS – In patients with hypercholesterolemia and high cardiovascular risk, the novel agent mipomersen administered as add-on therapy led to robust reductions in LDL cholesterol, based on the results of a double-blind, phase III study.

“In high-risk patients refractory to maximally tolerated statin therapy, the addition of mipomersen significantly reduced LDL-C and other atherogenic lipids and lipoproteins,” said Dr. William C. Cromwell of the Presbyterian Cardiovascular Institute in Charlotte, N.C.

Mipomersen is the first of a new class of agents called apolipoprotein B (apoB) synthesis inhibitors. In the study, the drug was administered subcutaneously once a week. Among its side effects were injection site reactions, increases in alanine aminotransferase (ALT) levels, and steatosis.

The study included 158 patients at high risk for cardiovascular events who were unable to achieve target LDL-C levels with statins, bile-acid sequestrants, and niacin. At baseline, all patients were on maximally tolerated doses of a statin; 63 were on the maximal approved dose, and 25 were also receiving ezetimibe.

All subjects had LDL-C levels of at least 100 mg/dL and triglycerides below 200 mg/dL. They were randomized 2:1 to 200 mg mipomersen or placebo weekly for 26 weeks. The primary end point was percent change in LDL-C from baseline at week 28 or 2 weeks after the last dose if treatment was not completed.

LDL-C levels of less than 100 mg/dL were achieved by 77 (76%) mipomersen-treated patients, compared with 19 (38%) placebo-treated patients. LDL-C levels of less than 70 mg/dL were achieved by 51 (50%) and 4 (8%), respectively.

The percent reduction in LDL cholesterol from baseline to the primary efficacy time point was a 37% drop in the mipomersen arm and a 5% drop in the placebo arm, a significant difference.

“LDL-C levels decreased through the first 17 weeks of treatment and remained relatively low through week 28,” Dr. Cromwell observed. “Mipomersen's lipid-lowering effects were independent of baseline LDL-C or race, and were similar for patients with and without diabetes.”

The effect of the drug in the diabetic subset was robust. In the diabetes cohort, the mean decline in LDL-C from baseline was 51% for the 56 patients on mipomersen and 32% for the 29 on placebo.

Mipomersen also was associated with significant reductions from baseline values in apoB (38%), total cholesterol (26%), non-HDL cholesterol (36%), and lipoprotein(a) (24%). HDL-C levels did not change significantly from baseline.

Sixty of the 105 mipomersen-treated patients (57%) and 44 of 52 placebo patients (85%) completed treatment. A total of 26 mipomersen-treated patients and 2 placebo-treated patients discontinued as a result of on-treatment adverse events. Of the mipomersen noncompleters, seven discontinued because of a liver enzyme-related adverse event, and seven stopped because of an injection site reaction.

Injection site reactions were the most common adverse event, occurring in 78% of the mipomersen group and 31% of the placebo group. Flu-like symptoms occurred in 34% and 21%, respectively. “Injection site reaction is the biggest side effect with this drug. This ranges from induration to redness, and some patients have skin discoloration,” Dr. Cromwell acknowledged.

ALT elevations at least 3 times the upper limit of normal were observed in 14% of patients on mipomersen, versus none receiving placebo, but this occurred without concomitant significant bilirubin elevations, he said. For 10% of patients, ALT elevations occurred on consecutive measurements at least 7 days apart.

Approximately one-third of patients had an increase in steatosis, defined as liver fat increasing by at least 5%; median percent change from baseline was 15%. “This does not represent a huge accumulation of fat. Instead, it is a signal that it's there at 28 weeks, and it is not particularly worrying. In a series of patients with much longer exposures, there is a plateau in this increase.”

Dr. Patrick Moriarty, a lipid specialist and professor of medicine at the University of Kansas, Kansas City, commented, “We treat many refractory patients, and I can tell you that a drug of this class is very much needed in this patient population. It will help get their lipid numbers down.”

The fact that patients achieve good LDL-C reductions on top of statin therapy is very encouraging, he said, noting, “The drug is not for every patient, but it could fill the need for an effective treatment in a small subset.”

Dr. Moriarty said the injectable delivery will not be a barrier to acceptance. “Patients can do these injections themselves, just like diabetes patients do. In studies I've participated in, we offer patients the opportunity to have the nurse give them the injections but most patients learn to do [the injections] themselves.”

Major Finding: After adjustment for multiple risk factors, severity of illness and extent of ECG changes, patients with suspected STEMI who did not arrive by ambulance at the emergency department spent 62% more time in the emergency department before undergoing catheterization.

Data Source: A study of 356 consecutive patients referred for emergent cardiac catheterization for a suspected STEMI by emergency physicians at a tertiary care hospital and a county hospital in San Francisco in 2009.

Disclosures: Dr. McCabe and Dr. Wright reported no relevant conflicts of interest.

NEW ORLEANS – Patients with suspected ST-elevation myocardial infarction who called an ambulance received lifesaving care in half the time as patients who got to the hospital by other means, according to a study conducted at two San Francisco hospitals.

“Patients who take an ambulance get a prehospital ECG,” said lead investigator Dr. James M. McCabe of the University of California, San Francisco, at the meeting. “These patients move through the emergency room and get to the cath lab much faster.”

“We found that almost half of patients referred for a potential heart attack don't take an ambulance but come in on their own, and it turns out they are doing themselves a great disservice,” Dr. McCabe said.

The study analyzed 356 consecutive patients referred for emergent cardiac catheterization for a suspected STEMI by emergency physicians at a tertiary care hospital and a county hospital in 2009. Of the 356 patients, 199 (56%) arrived by ambulance and 157 (44%) did not.

Variables affecting the time interval from the inciting ECG to STEMI pager activation, and door-to-balloon time, were analyzed in univariate and stepwise multivariate regression models.

All components of care were affected.

“The ultimate metric, door-to-balloon time, was reduced by 26% in patients taken by ambulance,” Dr. McCabe reported. This highly significant finding is important because studies show mortality risks are higher when door-to-balloon times exceed 90 minutes, he added.

The investigators then broke down the door-to-balloon time into its various components and compared the groups. After adjusting for demographic factors, traditional cardiovascular risk factors, severity of illness and extent of ECG changes, merely not presenting by ambulance to the emergency department (ED), and therefore not receiving a prehospital ECG, significantly lengthened by 62% the total time in the ED before undergoing catheterization.

Among patients arriving by ambulance, “each interval that occurred within the emergency room was reduced by more than 50%,” he reported.

The procedural time for revascularization, however, did not vary based on how the patient arrived at the hospital. This finding supports the conclusion that care was made more efficient prior to the catheterization itself, he said.

The one observable difference was that patients arriving by ambulance were more critically ill. They had more cardiac arrests, and required more cardiopulmonary resuscitation and intubation. “While these patients are sicker and require more care in the ER, they are still getting through the ER faster, after adjusting for multiple risk factors and elements in the decision-making process,” Dr. McCabe noted. “Taking the ambulance results in efficiency, and this translates into faster ER throughput and shorter door-to-balloon times.”

Of some concern to the researchers was that calling 911 did not ensure that patients with suspected STEMI arrived at the hospital with ECG results in hand. Among the 356 patients in the study, 68% did not receive an ECG, either because they did not travel by ambulance or because, in 43% of the cases, they were not given an ECG en route.

Dr. McCabe suspects that patients who did not receive an ECG in the ambulance may have had vague presenting symptoms when paramedics arrived. Of patients with symptoms more indicative of an MI, 78% got an ECG in the ambulance, he said.

“Our community is diverse, and we feel that barriers in communication with non–English speakers may also have played a role,” he added.

He further noted that in San Francisco, paramedics did not have the technology to forward the ECGs electronically to the receiving hospital. San Francisco will be implementing citywide remote transmission of ECGs soon, and the investigators plan to study whether this makes for even more efficient transfer of STEMI patients to the cath lab.

“These data suggest better triage systems may be necessary for patients with likely STEMIs, particularly for [more than] 40% of patients who do not arrive by ambulance,” Dr. McCabe concluded.

Dr. Janet Wright, ACC senior vice president of science and quality, said that “This is a safety message for patients: 'Your local ER wants you to come by ambulance!' And for physicians and health care systems, the message is that there are critical intervals within the overall pattern of care that need scrutiny,” said Dr. Wright, a cardiologist in Chico, Calif. “The person who arrives by private transportation may languish within those time intervals,” she said. “The message is to focus on every handoff. They accumulate in precious minutes.”

Patients who arrive by ambulance at the ED get to the cath lab faster than do those arriving by other means.

Source ©Aaron Kohr/iStockphoto.com

Major Finding: After adjustment for multiple risk factors, severity of illness and extent of ECG changes, patients with suspected STEMI who did not arrive by ambulance at the emergency department spent 62% more time in the emergency department before undergoing catheterization.

Data Source: A study of 356 consecutive patients referred for emergent cardiac catheterization for a suspected STEMI by emergency physicians at a tertiary care hospital and a county hospital in San Francisco in 2009.

Disclosures: Dr. McCabe and Dr. Wright reported no relevant conflicts of interest.

NEW ORLEANS – Patients with suspected ST-elevation myocardial infarction who called an ambulance received lifesaving care in half the time as patients who got to the hospital by other means, according to a study conducted at two San Francisco hospitals.

“Patients who take an ambulance get a prehospital ECG,” said lead investigator Dr. James M. McCabe of the University of California, San Francisco, at the meeting. “These patients move through the emergency room and get to the cath lab much faster.”

“We found that almost half of patients referred for a potential heart attack don't take an ambulance but come in on their own, and it turns out they are doing themselves a great disservice,” Dr. McCabe said.

The study analyzed 356 consecutive patients referred for emergent cardiac catheterization for a suspected STEMI by emergency physicians at a tertiary care hospital and a county hospital in 2009. Of the 356 patients, 199 (56%) arrived by ambulance and 157 (44%) did not.

Variables affecting the time interval from the inciting ECG to STEMI pager activation, and door-to-balloon time, were analyzed in univariate and stepwise multivariate regression models.

All components of care were affected.

“The ultimate metric, door-to-balloon time, was reduced by 26% in patients taken by ambulance,” Dr. McCabe reported. This highly significant finding is important because studies show mortality risks are higher when door-to-balloon times exceed 90 minutes, he added.

The investigators then broke down the door-to-balloon time into its various components and compared the groups. After adjusting for demographic factors, traditional cardiovascular risk factors, severity of illness and extent of ECG changes, merely not presenting by ambulance to the emergency department (ED), and therefore not receiving a prehospital ECG, significantly lengthened by 62% the total time in the ED before undergoing catheterization.

Among patients arriving by ambulance, “each interval that occurred within the emergency room was reduced by more than 50%,” he reported.

The procedural time for revascularization, however, did not vary based on how the patient arrived at the hospital. This finding supports the conclusion that care was made more efficient prior to the catheterization itself, he said.

The one observable difference was that patients arriving by ambulance were more critically ill. They had more cardiac arrests, and required more cardiopulmonary resuscitation and intubation. “While these patients are sicker and require more care in the ER, they are still getting through the ER faster, after adjusting for multiple risk factors and elements in the decision-making process,” Dr. McCabe noted. “Taking the ambulance results in efficiency, and this translates into faster ER throughput and shorter door-to-balloon times.”

Of some concern to the researchers was that calling 911 did not ensure that patients with suspected STEMI arrived at the hospital with ECG results in hand. Among the 356 patients in the study, 68% did not receive an ECG, either because they did not travel by ambulance or because, in 43% of the cases, they were not given an ECG en route.

Dr. McCabe suspects that patients who did not receive an ECG in the ambulance may have had vague presenting symptoms when paramedics arrived. Of patients with symptoms more indicative of an MI, 78% got an ECG in the ambulance, he said.

“Our community is diverse, and we feel that barriers in communication with non–English speakers may also have played a role,” he added.

He further noted that in San Francisco, paramedics did not have the technology to forward the ECGs electronically to the receiving hospital. San Francisco will be implementing citywide remote transmission of ECGs soon, and the investigators plan to study whether this makes for even more efficient transfer of STEMI patients to the cath lab.

“These data suggest better triage systems may be necessary for patients with likely STEMIs, particularly for [more than] 40% of patients who do not arrive by ambulance,” Dr. McCabe concluded.

Dr. Janet Wright, ACC senior vice president of science and quality, said that “This is a safety message for patients: 'Your local ER wants you to come by ambulance!' And for physicians and health care systems, the message is that there are critical intervals within the overall pattern of care that need scrutiny,” said Dr. Wright, a cardiologist in Chico, Calif. “The person who arrives by private transportation may languish within those time intervals,” she said. “The message is to focus on every handoff. They accumulate in precious minutes.”

Patients who arrive by ambulance at the ED get to the cath lab faster than do those arriving by other means.

Source ©Aaron Kohr/iStockphoto.com

Major Finding: After adjustment for multiple risk factors, severity of illness and extent of ECG changes, patients with suspected STEMI who did not arrive by ambulance at the emergency department spent 62% more time in the emergency department before undergoing catheterization.

Data Source: A study of 356 consecutive patients referred for emergent cardiac catheterization for a suspected STEMI by emergency physicians at a tertiary care hospital and a county hospital in San Francisco in 2009.

Disclosures: Dr. McCabe and Dr. Wright reported no relevant conflicts of interest.

NEW ORLEANS – Patients with suspected ST-elevation myocardial infarction who called an ambulance received lifesaving care in half the time as patients who got to the hospital by other means, according to a study conducted at two San Francisco hospitals.

“Patients who take an ambulance get a prehospital ECG,” said lead investigator Dr. James M. McCabe of the University of California, San Francisco, at the meeting. “These patients move through the emergency room and get to the cath lab much faster.”

“We found that almost half of patients referred for a potential heart attack don't take an ambulance but come in on their own, and it turns out they are doing themselves a great disservice,” Dr. McCabe said.

The study analyzed 356 consecutive patients referred for emergent cardiac catheterization for a suspected STEMI by emergency physicians at a tertiary care hospital and a county hospital in 2009. Of the 356 patients, 199 (56%) arrived by ambulance and 157 (44%) did not.

Variables affecting the time interval from the inciting ECG to STEMI pager activation, and door-to-balloon time, were analyzed in univariate and stepwise multivariate regression models.

All components of care were affected.

“The ultimate metric, door-to-balloon time, was reduced by 26% in patients taken by ambulance,” Dr. McCabe reported. This highly significant finding is important because studies show mortality risks are higher when door-to-balloon times exceed 90 minutes, he added.

The investigators then broke down the door-to-balloon time into its various components and compared the groups. After adjusting for demographic factors, traditional cardiovascular risk factors, severity of illness and extent of ECG changes, merely not presenting by ambulance to the emergency department (ED), and therefore not receiving a prehospital ECG, significantly lengthened by 62% the total time in the ED before undergoing catheterization.

Among patients arriving by ambulance, “each interval that occurred within the emergency room was reduced by more than 50%,” he reported.

The procedural time for revascularization, however, did not vary based on how the patient arrived at the hospital. This finding supports the conclusion that care was made more efficient prior to the catheterization itself, he said.

The one observable difference was that patients arriving by ambulance were more critically ill. They had more cardiac arrests, and required more cardiopulmonary resuscitation and intubation. “While these patients are sicker and require more care in the ER, they are still getting through the ER faster, after adjusting for multiple risk factors and elements in the decision-making process,” Dr. McCabe noted. “Taking the ambulance results in efficiency, and this translates into faster ER throughput and shorter door-to-balloon times.”

Of some concern to the researchers was that calling 911 did not ensure that patients with suspected STEMI arrived at the hospital with ECG results in hand. Among the 356 patients in the study, 68% did not receive an ECG, either because they did not travel by ambulance or because, in 43% of the cases, they were not given an ECG en route.

Dr. McCabe suspects that patients who did not receive an ECG in the ambulance may have had vague presenting symptoms when paramedics arrived. Of patients with symptoms more indicative of an MI, 78% got an ECG in the ambulance, he said.

“Our community is diverse, and we feel that barriers in communication with non–English speakers may also have played a role,” he added.

He further noted that in San Francisco, paramedics did not have the technology to forward the ECGs electronically to the receiving hospital. San Francisco will be implementing citywide remote transmission of ECGs soon, and the investigators plan to study whether this makes for even more efficient transfer of STEMI patients to the cath lab.

“These data suggest better triage systems may be necessary for patients with likely STEMIs, particularly for [more than] 40% of patients who do not arrive by ambulance,” Dr. McCabe concluded.

Dr. Janet Wright, ACC senior vice president of science and quality, said that “This is a safety message for patients: 'Your local ER wants you to come by ambulance!' And for physicians and health care systems, the message is that there are critical intervals within the overall pattern of care that need scrutiny,” said Dr. Wright, a cardiologist in Chico, Calif. “The person who arrives by private transportation may languish within those time intervals,” she said. “The message is to focus on every handoff. They accumulate in precious minutes.”

Patients who arrive by ambulance at the ED get to the cath lab faster than do those arriving by other means.

Source ©Aaron Kohr/iStockphoto.com

Major Finding: At 2 years, the composite primary efficacy end point of freedom from death, MV surgery for valve dysfunction (for device patients) or reoperation (for surgery patients), and MR greater than 2+ at 12 months was met by 52% of the percutaneous group and by 66% of the surgery group.

Data Source: A prospective, multi-center, randomized controlled phase II trial of 279 patients with 3+ or 4+ mitral regurgitation.

Disclosures: Dr. Feldman reported consulting fees, honoraria, and research grants from Abbott Vascular. Dr. Stone reported consulting fees and honoraria from Abbott Vascular and numerous other pharmaceutical and device companies. Dr. Bolling reported no relevant disclosures.

NEW ORLEANS – The durability and safety of treating mitral regurgitation with a percutaneous device as compared with that of surgical repair or replacement persisted at 2 years, according to an updated analysis of the EVEREST II trial results presented at the meeting.

“Our fundamental finding is that outcomes are very stable between 1 and 2 years of follow-up,” Dr. Ted Feldman, principal investigator, announced at a press briefing.

“The Kaplan-Meier curves for mortality and reoperation remain literally and completely flat through that time period, and clinical outcomes are durable,” he said.

On the basis of data from the first year of the study, percutaneous repair with the MitraClip was safer than surgery, but surgery yielded more complete reduction in mitral regurgitation (N. Engl. J. Med. 2011;364:1395-1406).

The 2-year results, presented at the meeting, show that both approaches reduced mitral regurgitation, and meaningful clinical benefits persisted, said Dr. Feldman, who is director of the cardiac catheterization laboratory at the NorthShore University HealthSystem in Evanston, Ill.

Clinical outcome measures at 2 years' follow-up showed that mitral regurgitation grade and left ventricular volumes remained stable between 1 and 2 years in both groups. The inter-group comparison showed a more favorable reduction in mitral regurgitation and a greater reduction in left ventricular diastolic volume with surgery at 1 and 2 years, and no difference in systolic volume reduction.

Also, New York Heart Association (NYHA) functional class was stable between years 1 and 2.

“Interestingly, the intergroup comparison showed a more favorable NYHA class outcome at both years with the clip,” Dr. Feldman reported.

The safety profile continued to be favorable, as well. “We saw no percutaneous device embolization; no device fracture, erosion, or migration; and no additional occurrence of single leaflet device attachment,” he reported.

“Stability is the major message in the examination of 2-year outcomes,” Dr. Feldman said.

“The randomized trial represents our very early experience with the device. Our procedural rate was 86% in the trial but in the postrandomization registry is in the 96% range. We are certainly going to get better at doing this.”

At a panel convened to comment on the study results, Dr. Gregg W. Stone, professor of medicine at New York Presbyterian Hospital and Columbia University, New York, said that the follow-up analysis of EVEREST II is “very well done” and has, “for the most part, shown stability and fairly comparable mortality, though 22% of patients still need surgery if they take the route of the percutaneous option.”

Dr. Steven F. Bolling, professor of surgery at the University of Michigan, Ann Arbor, maintained that while EVEREST II “suffers a little from awkward analyses,” the results are promising, pending the right patient selection and longer follow-up.

Patients at high surgical risk and those with cardiomyopathy-associated MR would be the appropriate subset for further study in order to refine the optimal use of the device, said Dr. Bolling.

EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) is a prospective, multicenter, randomized controlled phase II trial comparing the safety and efficacy of the MitraClip System with mitral valve surgery in the treatment of mitral regurgitation. The study enrolled 279 patients with 3+ or 4+ mitral regurgitation who were either symptomatic or were asymptomatic with a baseline left ejection fraction of 60%; 27% had functional mitral regurgitation and 73% had degenerative mitral regurgitation. Approximately half of the patients had NYHA functional class III or IV heart failure.

The patients were randomized 2:1 to receive the MitraClip device (n = 184) or mitral valve (MV) repair or replacement (n = 95). More than 90% of the study cohort was available for the 2-year analysis.

Outcomes through 1 year (primary safety and efficacy end points) were recently reported (N. Engl. J. Med. 2011; 364:1395-406), showing increased safety with the MitraClip device compared to surgery, but greater reduction in mitral regurgitation with surgery. At 30 days, major adverse events occurred in 15% of the percutaneous arm versus 48% of the surgical arm. Left ventricular function improved in both groups, as did NYHA) functional class and quality of life at 1 year.

At the meeting, Dr. Feldman presented two analyses of the 2-year data. The first was an intention-to-treat analysis, in which any mitral valve surgery following percutaneous repair was considered an end-point event.

The second analysis was a comparison of treatment strategies, in which MV surgery following unsuccessful in-hospital percutaneous repair was not considered an end point event. In the latter analysis, subsequent surgery within 90 days of the percutaneous procedure was still considered a “success” for the MitraClip.

The composite primary efficacy end point was freedom from death, MV surgery for valve dysfunction (for device patients) or reoperation (for surgery patients), and mitral regurgitation greater than 2+ at 12 months.

In the intention-to-treat analysis, the primary composite end point was met at 2 years by 52% of the percutaneous group and by 66% of the surgery group; in the 1-year analysis, these figures were 55% and 73%, respectively.

More patients receiving the clip later had MV surgery (22%), compared with the few patients in the surgery arm who required reoperation (3.6%). There was no significant difference in mortality or recurrent mitral regurgitation.

In the second analysis, there was no statistical difference in the effectiveness end point between the two arms of the study.

“When subsequent surgery within 90 days on device patients is considered a success, we see similarly stable results at 1 and 2 years,” he noted.

In this analysis, the primary end point was met at 2 years by 63% of the percutaneous group and by 66% of the surgery group.

When the subsequent need for MV surgery is removed as an end-point event, 6.2% of the percutaneous group and 3.6% of the surgery group had MV surgery or reoperation.

There was no difference in the Kaplan-Meier mortality plot for the intention-to-treat analysis at any time point, he stressed. At 1 year, 95% of the patients in each arm were alive; at 2 years, 91% of the surgery arm and 90% of the percutaneous arm were still alive.

The Kaplan-Meier plot for freedom from MV surgery/reoperation, however, favored the surgical arm: 96% versus 78% at 2 years.

The “need for surgery in patients in the clip group was almost entirely in the first several months after therapy, and after 6 months the curves overlapped at 1 and 2 years,” he observed.

“Importantly, 78% of device patients are free from MV surgery at 2 years,” noted Dr. Feldman.

When these early failures were excluded, there were no differences in the need for MV surgery or for reoperation.

At the press conference, Dr. Feldman explained that the two analyses “answer different questions.”

“The intention-to-treat analysis gives the patient the odds of success with the clip at the end of the year,” he explained. “It tells them that 78% will be free of the need for surgery at 2 years, and 97% will have NYHA functional class I or II.”

The second analysis answers the question, “What if I am in the 20% needing surgery?” That analysis counts the combined strategy of the clip, with surgery as needed.

'Stability is the major message in the examination of 2-year outcomes' of percutaneous repair.

Source DR. FELDMAN

Major Finding: At 2 years, the composite primary efficacy end point of freedom from death, MV surgery for valve dysfunction (for device patients) or reoperation (for surgery patients), and MR greater than 2+ at 12 months was met by 52% of the percutaneous group and by 66% of the surgery group.

Data Source: A prospective, multi-center, randomized controlled phase II trial of 279 patients with 3+ or 4+ mitral regurgitation.

Disclosures: Dr. Feldman reported consulting fees, honoraria, and research grants from Abbott Vascular. Dr. Stone reported consulting fees and honoraria from Abbott Vascular and numerous other pharmaceutical and device companies. Dr. Bolling reported no relevant disclosures.

NEW ORLEANS – The durability and safety of treating mitral regurgitation with a percutaneous device as compared with that of surgical repair or replacement persisted at 2 years, according to an updated analysis of the EVEREST II trial results presented at the meeting.

“Our fundamental finding is that outcomes are very stable between 1 and 2 years of follow-up,” Dr. Ted Feldman, principal investigator, announced at a press briefing.

“The Kaplan-Meier curves for mortality and reoperation remain literally and completely flat through that time period, and clinical outcomes are durable,” he said.

On the basis of data from the first year of the study, percutaneous repair with the MitraClip was safer than surgery, but surgery yielded more complete reduction in mitral regurgitation (N. Engl. J. Med. 2011;364:1395-1406).

The 2-year results, presented at the meeting, show that both approaches reduced mitral regurgitation, and meaningful clinical benefits persisted, said Dr. Feldman, who is director of the cardiac catheterization laboratory at the NorthShore University HealthSystem in Evanston, Ill.

Clinical outcome measures at 2 years' follow-up showed that mitral regurgitation grade and left ventricular volumes remained stable between 1 and 2 years in both groups. The inter-group comparison showed a more favorable reduction in mitral regurgitation and a greater reduction in left ventricular diastolic volume with surgery at 1 and 2 years, and no difference in systolic volume reduction.

Also, New York Heart Association (NYHA) functional class was stable between years 1 and 2.

“Interestingly, the intergroup comparison showed a more favorable NYHA class outcome at both years with the clip,” Dr. Feldman reported.

The safety profile continued to be favorable, as well. “We saw no percutaneous device embolization; no device fracture, erosion, or migration; and no additional occurrence of single leaflet device attachment,” he reported.

“Stability is the major message in the examination of 2-year outcomes,” Dr. Feldman said.

“The randomized trial represents our very early experience with the device. Our procedural rate was 86% in the trial but in the postrandomization registry is in the 96% range. We are certainly going to get better at doing this.”

At a panel convened to comment on the study results, Dr. Gregg W. Stone, professor of medicine at New York Presbyterian Hospital and Columbia University, New York, said that the follow-up analysis of EVEREST II is “very well done” and has, “for the most part, shown stability and fairly comparable mortality, though 22% of patients still need surgery if they take the route of the percutaneous option.”

Dr. Steven F. Bolling, professor of surgery at the University of Michigan, Ann Arbor, maintained that while EVEREST II “suffers a little from awkward analyses,” the results are promising, pending the right patient selection and longer follow-up.

Patients at high surgical risk and those with cardiomyopathy-associated MR would be the appropriate subset for further study in order to refine the optimal use of the device, said Dr. Bolling.

EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) is a prospective, multicenter, randomized controlled phase II trial comparing the safety and efficacy of the MitraClip System with mitral valve surgery in the treatment of mitral regurgitation. The study enrolled 279 patients with 3+ or 4+ mitral regurgitation who were either symptomatic or were asymptomatic with a baseline left ejection fraction of 60%; 27% had functional mitral regurgitation and 73% had degenerative mitral regurgitation. Approximately half of the patients had NYHA functional class III or IV heart failure.

The patients were randomized 2:1 to receive the MitraClip device (n = 184) or mitral valve (MV) repair or replacement (n = 95). More than 90% of the study cohort was available for the 2-year analysis.

Outcomes through 1 year (primary safety and efficacy end points) were recently reported (N. Engl. J. Med. 2011; 364:1395-406), showing increased safety with the MitraClip device compared to surgery, but greater reduction in mitral regurgitation with surgery. At 30 days, major adverse events occurred in 15% of the percutaneous arm versus 48% of the surgical arm. Left ventricular function improved in both groups, as did NYHA) functional class and quality of life at 1 year.

At the meeting, Dr. Feldman presented two analyses of the 2-year data. The first was an intention-to-treat analysis, in which any mitral valve surgery following percutaneous repair was considered an end-point event.

The second analysis was a comparison of treatment strategies, in which MV surgery following unsuccessful in-hospital percutaneous repair was not considered an end point event. In the latter analysis, subsequent surgery within 90 days of the percutaneous procedure was still considered a “success” for the MitraClip.

The composite primary efficacy end point was freedom from death, MV surgery for valve dysfunction (for device patients) or reoperation (for surgery patients), and mitral regurgitation greater than 2+ at 12 months.

In the intention-to-treat analysis, the primary composite end point was met at 2 years by 52% of the percutaneous group and by 66% of the surgery group; in the 1-year analysis, these figures were 55% and 73%, respectively.

More patients receiving the clip later had MV surgery (22%), compared with the few patients in the surgery arm who required reoperation (3.6%). There was no significant difference in mortality or recurrent mitral regurgitation.

In the second analysis, there was no statistical difference in the effectiveness end point between the two arms of the study.

“When subsequent surgery within 90 days on device patients is considered a success, we see similarly stable results at 1 and 2 years,” he noted.

In this analysis, the primary end point was met at 2 years by 63% of the percutaneous group and by 66% of the surgery group.

When the subsequent need for MV surgery is removed as an end-point event, 6.2% of the percutaneous group and 3.6% of the surgery group had MV surgery or reoperation.

There was no difference in the Kaplan-Meier mortality plot for the intention-to-treat analysis at any time point, he stressed. At 1 year, 95% of the patients in each arm were alive; at 2 years, 91% of the surgery arm and 90% of the percutaneous arm were still alive.

The Kaplan-Meier plot for freedom from MV surgery/reoperation, however, favored the surgical arm: 96% versus 78% at 2 years.

The “need for surgery in patients in the clip group was almost entirely in the first several months after therapy, and after 6 months the curves overlapped at 1 and 2 years,” he observed.

“Importantly, 78% of device patients are free from MV surgery at 2 years,” noted Dr. Feldman.

When these early failures were excluded, there were no differences in the need for MV surgery or for reoperation.

At the press conference, Dr. Feldman explained that the two analyses “answer different questions.”

“The intention-to-treat analysis gives the patient the odds of success with the clip at the end of the year,” he explained. “It tells them that 78% will be free of the need for surgery at 2 years, and 97% will have NYHA functional class I or II.”

The second analysis answers the question, “What if I am in the 20% needing surgery?” That analysis counts the combined strategy of the clip, with surgery as needed.

'Stability is the major message in the examination of 2-year outcomes' of percutaneous repair.

Source DR. FELDMAN

Major Finding: At 2 years, the composite primary efficacy end point of freedom from death, MV surgery for valve dysfunction (for device patients) or reoperation (for surgery patients), and MR greater than 2+ at 12 months was met by 52% of the percutaneous group and by 66% of the surgery group.

Data Source: A prospective, multi-center, randomized controlled phase II trial of 279 patients with 3+ or 4+ mitral regurgitation.

Disclosures: Dr. Feldman reported consulting fees, honoraria, and research grants from Abbott Vascular. Dr. Stone reported consulting fees and honoraria from Abbott Vascular and numerous other pharmaceutical and device companies. Dr. Bolling reported no relevant disclosures.

NEW ORLEANS – The durability and safety of treating mitral regurgitation with a percutaneous device as compared with that of surgical repair or replacement persisted at 2 years, according to an updated analysis of the EVEREST II trial results presented at the meeting.

“Our fundamental finding is that outcomes are very stable between 1 and 2 years of follow-up,” Dr. Ted Feldman, principal investigator, announced at a press briefing.

“The Kaplan-Meier curves for mortality and reoperation remain literally and completely flat through that time period, and clinical outcomes are durable,” he said.

On the basis of data from the first year of the study, percutaneous repair with the MitraClip was safer than surgery, but surgery yielded more complete reduction in mitral regurgitation (N. Engl. J. Med. 2011;364:1395-1406).

The 2-year results, presented at the meeting, show that both approaches reduced mitral regurgitation, and meaningful clinical benefits persisted, said Dr. Feldman, who is director of the cardiac catheterization laboratory at the NorthShore University HealthSystem in Evanston, Ill.

Clinical outcome measures at 2 years' follow-up showed that mitral regurgitation grade and left ventricular volumes remained stable between 1 and 2 years in both groups. The inter-group comparison showed a more favorable reduction in mitral regurgitation and a greater reduction in left ventricular diastolic volume with surgery at 1 and 2 years, and no difference in systolic volume reduction.

Also, New York Heart Association (NYHA) functional class was stable between years 1 and 2.

“Interestingly, the intergroup comparison showed a more favorable NYHA class outcome at both years with the clip,” Dr. Feldman reported.

The safety profile continued to be favorable, as well. “We saw no percutaneous device embolization; no device fracture, erosion, or migration; and no additional occurrence of single leaflet device attachment,” he reported.

“Stability is the major message in the examination of 2-year outcomes,” Dr. Feldman said.

“The randomized trial represents our very early experience with the device. Our procedural rate was 86% in the trial but in the postrandomization registry is in the 96% range. We are certainly going to get better at doing this.”

At a panel convened to comment on the study results, Dr. Gregg W. Stone, professor of medicine at New York Presbyterian Hospital and Columbia University, New York, said that the follow-up analysis of EVEREST II is “very well done” and has, “for the most part, shown stability and fairly comparable mortality, though 22% of patients still need surgery if they take the route of the percutaneous option.”

Dr. Steven F. Bolling, professor of surgery at the University of Michigan, Ann Arbor, maintained that while EVEREST II “suffers a little from awkward analyses,” the results are promising, pending the right patient selection and longer follow-up.

Patients at high surgical risk and those with cardiomyopathy-associated MR would be the appropriate subset for further study in order to refine the optimal use of the device, said Dr. Bolling.

EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) is a prospective, multicenter, randomized controlled phase II trial comparing the safety and efficacy of the MitraClip System with mitral valve surgery in the treatment of mitral regurgitation. The study enrolled 279 patients with 3+ or 4+ mitral regurgitation who were either symptomatic or were asymptomatic with a baseline left ejection fraction of 60%; 27% had functional mitral regurgitation and 73% had degenerative mitral regurgitation. Approximately half of the patients had NYHA functional class III or IV heart failure.

The patients were randomized 2:1 to receive the MitraClip device (n = 184) or mitral valve (MV) repair or replacement (n = 95). More than 90% of the study cohort was available for the 2-year analysis.

Outcomes through 1 year (primary safety and efficacy end points) were recently reported (N. Engl. J. Med. 2011; 364:1395-406), showing increased safety with the MitraClip device compared to surgery, but greater reduction in mitral regurgitation with surgery. At 30 days, major adverse events occurred in 15% of the percutaneous arm versus 48% of the surgical arm. Left ventricular function improved in both groups, as did NYHA) functional class and quality of life at 1 year.

At the meeting, Dr. Feldman presented two analyses of the 2-year data. The first was an intention-to-treat analysis, in which any mitral valve surgery following percutaneous repair was considered an end-point event.

The second analysis was a comparison of treatment strategies, in which MV surgery following unsuccessful in-hospital percutaneous repair was not considered an end point event. In the latter analysis, subsequent surgery within 90 days of the percutaneous procedure was still considered a “success” for the MitraClip.

The composite primary efficacy end point was freedom from death, MV surgery for valve dysfunction (for device patients) or reoperation (for surgery patients), and mitral regurgitation greater than 2+ at 12 months.

In the intention-to-treat analysis, the primary composite end point was met at 2 years by 52% of the percutaneous group and by 66% of the surgery group; in the 1-year analysis, these figures were 55% and 73%, respectively.

More patients receiving the clip later had MV surgery (22%), compared with the few patients in the surgery arm who required reoperation (3.6%). There was no significant difference in mortality or recurrent mitral regurgitation.

In the second analysis, there was no statistical difference in the effectiveness end point between the two arms of the study.

“When subsequent surgery within 90 days on device patients is considered a success, we see similarly stable results at 1 and 2 years,” he noted.

In this analysis, the primary end point was met at 2 years by 63% of the percutaneous group and by 66% of the surgery group.

When the subsequent need for MV surgery is removed as an end-point event, 6.2% of the percutaneous group and 3.6% of the surgery group had MV surgery or reoperation.

There was no difference in the Kaplan-Meier mortality plot for the intention-to-treat analysis at any time point, he stressed. At 1 year, 95% of the patients in each arm were alive; at 2 years, 91% of the surgery arm and 90% of the percutaneous arm were still alive.

The Kaplan-Meier plot for freedom from MV surgery/reoperation, however, favored the surgical arm: 96% versus 78% at 2 years.

The “need for surgery in patients in the clip group was almost entirely in the first several months after therapy, and after 6 months the curves overlapped at 1 and 2 years,” he observed.

“Importantly, 78% of device patients are free from MV surgery at 2 years,” noted Dr. Feldman.

When these early failures were excluded, there were no differences in the need for MV surgery or for reoperation.

At the press conference, Dr. Feldman explained that the two analyses “answer different questions.”

“The intention-to-treat analysis gives the patient the odds of success with the clip at the end of the year,” he explained. “It tells them that 78% will be free of the need for surgery at 2 years, and 97% will have NYHA functional class I or II.”

The second analysis answers the question, “What if I am in the 20% needing surgery?” That analysis counts the combined strategy of the clip, with surgery as needed.

'Stability is the major message in the examination of 2-year outcomes' of percutaneous repair.

Source DR. FELDMAN

NEW ORLEANS – In major clinical trials of lipid-lowering agents, the mortality benefit derived from medical therapy persists long after the studies end, according to a meta-analysis presented at the annual meeting of the American College of Cardiology.

Furthermore, placebo recipients who cross over to lipid-lowering therapy in the open-label phases of the studies demonstrate survival benefits as well, but never attain the protection achieved by being randomized to active treatment earlier on, according to Dr. William J. Kostis of Massachusetts General Hospital, Boston. "Persons with risk factors for coronary artery disease should be treated early," Dr. Kostis said in an interview. "The sooner you treat, the better."

He and his colleagues searched several major databases to identify randomized trials of lipid-lowering therapies that also contained an analysis of patient outcomes after the randomized portion of the trials had ended and an open-label phase had begun. Active treatment in the trials involved statins, niacin, cholestyramine, or gemfibrozil.

The analysis included eight clinical trials involving 44,255 patients, of whom 8,144 died during follow-up.

The average patient remained on the assigned treatment for approximately 5 years and was on the lipid-lowering agent in the open-label phase for approximately 6 years.

During the randomized phase of the trials, the mean all-cause mortality was significantly lower for the active treatment group (odds ratio, 0.84; P = .0006), as was cardiovascular mortality (0.72; P less than .001). The lower mortality among those initially receiving active therapy persisted during the open-label follow-up phase (OR, 0.90; P = .0035), as did the reduction in cardiovascular mortality (OR, 0.82; P = .0014).

"Being treated with a beneficial medication for a longer period of time is better, possibly because we are arresting pathophysiology at an earlier stage," Dr. Kostis proposed. He added that statins may be reducing the size of infarcts in patients who have myocardial infarctions.

Dr. Patrick Moriarty, a lipid specialist and a professor of medicine at the University of Kansas in Kansas City, agreed. "We need to start lipid-lowering therapy early to get the most benefit," and this includes interventions in children when necessary, he added.

"We treat pediatric patients all the time," he said, "not only those with familial hyperlipidemias but also those with metabolic syndrome. ... The future emphasis will be, ‘the sooner the better.’ "

Dr. Kostis and Dr. Moriarty reported having no relevant conflicts of interest.

NEW ORLEANS – In major clinical trials of lipid-lowering agents, the mortality benefit derived from medical therapy persists long after the studies end, according to a meta-analysis presented at the annual meeting of the American College of Cardiology.

Furthermore, placebo recipients who cross over to lipid-lowering therapy in the open-label phases of the studies demonstrate survival benefits as well, but never attain the protection achieved by being randomized to active treatment earlier on, according to Dr. William J. Kostis of Massachusetts General Hospital, Boston. "Persons with risk factors for coronary artery disease should be treated early," Dr. Kostis said in an interview. "The sooner you treat, the better."

He and his colleagues searched several major databases to identify randomized trials of lipid-lowering therapies that also contained an analysis of patient outcomes after the randomized portion of the trials had ended and an open-label phase had begun. Active treatment in the trials involved statins, niacin, cholestyramine, or gemfibrozil.

The analysis included eight clinical trials involving 44,255 patients, of whom 8,144 died during follow-up.

The average patient remained on the assigned treatment for approximately 5 years and was on the lipid-lowering agent in the open-label phase for approximately 6 years.

During the randomized phase of the trials, the mean all-cause mortality was significantly lower for the active treatment group (odds ratio, 0.84; P = .0006), as was cardiovascular mortality (0.72; P less than .001). The lower mortality among those initially receiving active therapy persisted during the open-label follow-up phase (OR, 0.90; P = .0035), as did the reduction in cardiovascular mortality (OR, 0.82; P = .0014).

"Being treated with a beneficial medication for a longer period of time is better, possibly because we are arresting pathophysiology at an earlier stage," Dr. Kostis proposed. He added that statins may be reducing the size of infarcts in patients who have myocardial infarctions.

Dr. Patrick Moriarty, a lipid specialist and a professor of medicine at the University of Kansas in Kansas City, agreed. "We need to start lipid-lowering therapy early to get the most benefit," and this includes interventions in children when necessary, he added.

"We treat pediatric patients all the time," he said, "not only those with familial hyperlipidemias but also those with metabolic syndrome. ... The future emphasis will be, ‘the sooner the better.’ "

Dr. Kostis and Dr. Moriarty reported having no relevant conflicts of interest.

NEW ORLEANS – In major clinical trials of lipid-lowering agents, the mortality benefit derived from medical therapy persists long after the studies end, according to a meta-analysis presented at the annual meeting of the American College of Cardiology.

Furthermore, placebo recipients who cross over to lipid-lowering therapy in the open-label phases of the studies demonstrate survival benefits as well, but never attain the protection achieved by being randomized to active treatment earlier on, according to Dr. William J. Kostis of Massachusetts General Hospital, Boston. "Persons with risk factors for coronary artery disease should be treated early," Dr. Kostis said in an interview. "The sooner you treat, the better."

He and his colleagues searched several major databases to identify randomized trials of lipid-lowering therapies that also contained an analysis of patient outcomes after the randomized portion of the trials had ended and an open-label phase had begun. Active treatment in the trials involved statins, niacin, cholestyramine, or gemfibrozil.

The analysis included eight clinical trials involving 44,255 patients, of whom 8,144 died during follow-up.

The average patient remained on the assigned treatment for approximately 5 years and was on the lipid-lowering agent in the open-label phase for approximately 6 years.

During the randomized phase of the trials, the mean all-cause mortality was significantly lower for the active treatment group (odds ratio, 0.84; P = .0006), as was cardiovascular mortality (0.72; P less than .001). The lower mortality among those initially receiving active therapy persisted during the open-label follow-up phase (OR, 0.90; P = .0035), as did the reduction in cardiovascular mortality (OR, 0.82; P = .0014).

"Being treated with a beneficial medication for a longer period of time is better, possibly because we are arresting pathophysiology at an earlier stage," Dr. Kostis proposed. He added that statins may be reducing the size of infarcts in patients who have myocardial infarctions.

Dr. Patrick Moriarty, a lipid specialist and a professor of medicine at the University of Kansas in Kansas City, agreed. "We need to start lipid-lowering therapy early to get the most benefit," and this includes interventions in children when necessary, he added.

"We treat pediatric patients all the time," he said, "not only those with familial hyperlipidemias but also those with metabolic syndrome. ... The future emphasis will be, ‘the sooner the better.’ "

Dr. Kostis and Dr. Moriarty reported having no relevant conflicts of interest.

NEW ORLEANS – Short and standard durations of dual-antiplatelet therapy were equally protective against target vessel failure in drug-eluting stent recipients, Korean researchers reported at the annual meeting of the American College of Cardiology.

With the exception of patients who had diabetes, the overall 12-month clinical event rates were not different between 6-month and 12-month treatment duration groups for all-cause mortality, cardiac death, myocardial infarction, cerebrovascular accident, target vessel revascularization, stent thrombosis, major bleeding, or various composites of the above end points, reported Dr. Hyeon-Cheol Gwon of Samsung Medical Center at Sungkyunkwan University in Seoul.

"At least in low-risk patients getting drug-eluting stents, that is, nondiabetics, maybe we can safely discontinue clopidogrel at 6 months," he said. Current guidelines recommend at least 12 months of anticoagulation to prevent venous thromboembolism.

Early discontinuation of antiplatelet therapy might be particularly relevant for patients at high risk of bleeding or those anticipating subsequent procedures, which are often delayed while the drugs are withdrawn.

But Dr. Sanjay Kaul of Cedars-Sinai Medical Center, Los Angeles, an invited panelist at the late-breaking clinical trials session where the results were presented, questioned the researchers’ use of target vessel failure (TVF) as the primary study end point. TVF was defined as a composite of cardiac death, myocardial infarction, or target vessel revascularization.

Dr. Gwon acknowledged that "the study was underpowered to test the hard end points that we are really interested in. ... We recognize our study is hypothesis generating."

The trial involved 1,443 patients with greater than 50% stenosis and evidence of myocardial ischemia. Patients receiving everolimus- or sirolimus-eluting stents were randomized to receive 6 or 12 months of dual antiplatelet therapy with clopidogrel and aspirin.

The study found that discontinuing clopidogrel and aspirin after 6 months did not increase the rate of 12-month TVF. The rates were 4.7% for the 6-month group and 4.4% for the 12-month group. By Kaplan-Meier analysis, the cumulative proportional TVF estimate at 1 year was 5.2% for the 6-month regimen and 4.3% for the 12-month regimen, which met the noninferiority end point "in a highly significant manner with a confidence interval that was smaller than prespecified for noninferiority" (P = .0031; upper 1-sided 97.5% CI 0.9%-3.6%), Dr. Gwon said.

The cumulative incidence of major adverse cardiac or coronary events was 7.5% with 6-month therapy and 8.4% with 12-month therapy.

There was also no significant difference according to whether patients received an everolimus- or sirolimus-eluting stent, though the rates were numerically closer in the everolimus group.

There was, however, a significantly higher risk for primary TVF with early discontinuation of antiplatelet therapy for patients with diabetes. Diabetic patients receiving 6 months of dual antiplatelet therapy had a TVF rate of 8.9%, vs. 2.9% with 12 months of treatment (P = .006).

There were no other significant subgroup differences.

Crossovers were common, primarily in that patients on the 6-month regimen received clopidogrel for a longer duration than assigned. Non-inferiority between the arms was maintained in a per-protocol analysis of 936 patients that excluded patients who crossed over, were lost to follow-up or otherwise did not receive treatment as assigned.

The per-protocol analysis showed the cumulative proportional TVF estimates at 1 year to be 3.6% in the 6-month group and 4.3% in the 12-month group (P = .0093 for noninferiority). TVF incidence rates were 3.2% and 2.1%, respectively, Dr. Gwon reported.

Dr. Byron Lee of the University of California in San Francisco, noted at a press briefing, "Frequently, we are confronted by patients on clopidogrel and aspirin, and we may have to put a pacemaker or defibrillator in them. Knowing that this study showed noninferiority, I feel much more comfortable now taking them off clopidogrel if it’s been past 6 months."

Dr. Gwon reported consulting fees and honoraria from Cordis and Medtronic as well as research support from Abbott Korea and Medtronic Korea. Dr. Lee reported consulting fees and honoraria from Biotronik, St. Jude, and Nanostim, as well as research funding from Medtronic and Zoll. Dr. Kaul serves on the Food and Drug Administration’s Cardiorenal Advisory Panel and has received consulting fees and honoraria from Novo Nordisk and Hoffman-LaRoche.

NEW ORLEANS – Short and standard durations of dual-antiplatelet therapy were equally protective against target vessel failure in drug-eluting stent recipients, Korean researchers reported at the annual meeting of the American College of Cardiology.

With the exception of patients who had diabetes, the overall 12-month clinical event rates were not different between 6-month and 12-month treatment duration groups for all-cause mortality, cardiac death, myocardial infarction, cerebrovascular accident, target vessel revascularization, stent thrombosis, major bleeding, or various composites of the above end points, reported Dr. Hyeon-Cheol Gwon of Samsung Medical Center at Sungkyunkwan University in Seoul.

"At least in low-risk patients getting drug-eluting stents, that is, nondiabetics, maybe we can safely discontinue clopidogrel at 6 months," he said. Current guidelines recommend at least 12 months of anticoagulation to prevent venous thromboembolism.

Early discontinuation of antiplatelet therapy might be particularly relevant for patients at high risk of bleeding or those anticipating subsequent procedures, which are often delayed while the drugs are withdrawn.

But Dr. Sanjay Kaul of Cedars-Sinai Medical Center, Los Angeles, an invited panelist at the late-breaking clinical trials session where the results were presented, questioned the researchers’ use of target vessel failure (TVF) as the primary study end point. TVF was defined as a composite of cardiac death, myocardial infarction, or target vessel revascularization.

Dr. Gwon acknowledged that "the study was underpowered to test the hard end points that we are really interested in. ... We recognize our study is hypothesis generating."

The trial involved 1,443 patients with greater than 50% stenosis and evidence of myocardial ischemia. Patients receiving everolimus- or sirolimus-eluting stents were randomized to receive 6 or 12 months of dual antiplatelet therapy with clopidogrel and aspirin.

The study found that discontinuing clopidogrel and aspirin after 6 months did not increase the rate of 12-month TVF. The rates were 4.7% for the 6-month group and 4.4% for the 12-month group. By Kaplan-Meier analysis, the cumulative proportional TVF estimate at 1 year was 5.2% for the 6-month regimen and 4.3% for the 12-month regimen, which met the noninferiority end point "in a highly significant manner with a confidence interval that was smaller than prespecified for noninferiority" (P = .0031; upper 1-sided 97.5% CI 0.9%-3.6%), Dr. Gwon said.

The cumulative incidence of major adverse cardiac or coronary events was 7.5% with 6-month therapy and 8.4% with 12-month therapy.

There was also no significant difference according to whether patients received an everolimus- or sirolimus-eluting stent, though the rates were numerically closer in the everolimus group.

There was, however, a significantly higher risk for primary TVF with early discontinuation of antiplatelet therapy for patients with diabetes. Diabetic patients receiving 6 months of dual antiplatelet therapy had a TVF rate of 8.9%, vs. 2.9% with 12 months of treatment (P = .006).

There were no other significant subgroup differences.

Crossovers were common, primarily in that patients on the 6-month regimen received clopidogrel for a longer duration than assigned. Non-inferiority between the arms was maintained in a per-protocol analysis of 936 patients that excluded patients who crossed over, were lost to follow-up or otherwise did not receive treatment as assigned.

The per-protocol analysis showed the cumulative proportional TVF estimates at 1 year to be 3.6% in the 6-month group and 4.3% in the 12-month group (P = .0093 for noninferiority). TVF incidence rates were 3.2% and 2.1%, respectively, Dr. Gwon reported.

Dr. Byron Lee of the University of California in San Francisco, noted at a press briefing, "Frequently, we are confronted by patients on clopidogrel and aspirin, and we may have to put a pacemaker or defibrillator in them. Knowing that this study showed noninferiority, I feel much more comfortable now taking them off clopidogrel if it’s been past 6 months."

Dr. Gwon reported consulting fees and honoraria from Cordis and Medtronic as well as research support from Abbott Korea and Medtronic Korea. Dr. Lee reported consulting fees and honoraria from Biotronik, St. Jude, and Nanostim, as well as research funding from Medtronic and Zoll. Dr. Kaul serves on the Food and Drug Administration’s Cardiorenal Advisory Panel and has received consulting fees and honoraria from Novo Nordisk and Hoffman-LaRoche.

NEW ORLEANS – Short and standard durations of dual-antiplatelet therapy were equally protective against target vessel failure in drug-eluting stent recipients, Korean researchers reported at the annual meeting of the American College of Cardiology.

With the exception of patients who had diabetes, the overall 12-month clinical event rates were not different between 6-month and 12-month treatment duration groups for all-cause mortality, cardiac death, myocardial infarction, cerebrovascular accident, target vessel revascularization, stent thrombosis, major bleeding, or various composites of the above end points, reported Dr. Hyeon-Cheol Gwon of Samsung Medical Center at Sungkyunkwan University in Seoul.

"At least in low-risk patients getting drug-eluting stents, that is, nondiabetics, maybe we can safely discontinue clopidogrel at 6 months," he said. Current guidelines recommend at least 12 months of anticoagulation to prevent venous thromboembolism.

Early discontinuation of antiplatelet therapy might be particularly relevant for patients at high risk of bleeding or those anticipating subsequent procedures, which are often delayed while the drugs are withdrawn.

But Dr. Sanjay Kaul of Cedars-Sinai Medical Center, Los Angeles, an invited panelist at the late-breaking clinical trials session where the results were presented, questioned the researchers’ use of target vessel failure (TVF) as the primary study end point. TVF was defined as a composite of cardiac death, myocardial infarction, or target vessel revascularization.

Dr. Gwon acknowledged that "the study was underpowered to test the hard end points that we are really interested in. ... We recognize our study is hypothesis generating."

The trial involved 1,443 patients with greater than 50% stenosis and evidence of myocardial ischemia. Patients receiving everolimus- or sirolimus-eluting stents were randomized to receive 6 or 12 months of dual antiplatelet therapy with clopidogrel and aspirin.

The study found that discontinuing clopidogrel and aspirin after 6 months did not increase the rate of 12-month TVF. The rates were 4.7% for the 6-month group and 4.4% for the 12-month group. By Kaplan-Meier analysis, the cumulative proportional TVF estimate at 1 year was 5.2% for the 6-month regimen and 4.3% for the 12-month regimen, which met the noninferiority end point "in a highly significant manner with a confidence interval that was smaller than prespecified for noninferiority" (P = .0031; upper 1-sided 97.5% CI 0.9%-3.6%), Dr. Gwon said.

The cumulative incidence of major adverse cardiac or coronary events was 7.5% with 6-month therapy and 8.4% with 12-month therapy.

There was also no significant difference according to whether patients received an everolimus- or sirolimus-eluting stent, though the rates were numerically closer in the everolimus group.

There was, however, a significantly higher risk for primary TVF with early discontinuation of antiplatelet therapy for patients with diabetes. Diabetic patients receiving 6 months of dual antiplatelet therapy had a TVF rate of 8.9%, vs. 2.9% with 12 months of treatment (P = .006).

There were no other significant subgroup differences.

Crossovers were common, primarily in that patients on the 6-month regimen received clopidogrel for a longer duration than assigned. Non-inferiority between the arms was maintained in a per-protocol analysis of 936 patients that excluded patients who crossed over, were lost to follow-up or otherwise did not receive treatment as assigned.

The per-protocol analysis showed the cumulative proportional TVF estimates at 1 year to be 3.6% in the 6-month group and 4.3% in the 12-month group (P = .0093 for noninferiority). TVF incidence rates were 3.2% and 2.1%, respectively, Dr. Gwon reported.

Dr. Byron Lee of the University of California in San Francisco, noted at a press briefing, "Frequently, we are confronted by patients on clopidogrel and aspirin, and we may have to put a pacemaker or defibrillator in them. Knowing that this study showed noninferiority, I feel much more comfortable now taking them off clopidogrel if it’s been past 6 months."

Dr. Gwon reported consulting fees and honoraria from Cordis and Medtronic as well as research support from Abbott Korea and Medtronic Korea. Dr. Lee reported consulting fees and honoraria from Biotronik, St. Jude, and Nanostim, as well as research funding from Medtronic and Zoll. Dr. Kaul serves on the Food and Drug Administration’s Cardiorenal Advisory Panel and has received consulting fees and honoraria from Novo Nordisk and Hoffman-LaRoche.

NEW ORLEANS – Prevention of major cardiovascular events was similar in a comparison of valsartan and amlodipine in patients with hypertension and diabetes or glucose intolerance, according to a Japanese study presented April 5 at the annual meeting of the American College of Cardiology.

The Novel Antihypertensive Goal of Hypertension With Diabetes – Hypertensive Events and ARB Treatment (NAGOYA-HEART) Study is the first randomized trial to compare the effects of an angiotensin II receptor blocker (ARB) with a calcium channel blocker (CCB) on cardiovascular outcomes in this patient population. No significant differences were found between the two classes, reported Dr. Toyoaki Murohara of Nagoya (Japan) University.

"Our study showed no difference in the efficacies between the ARB and the CCB in terms of prevention of major cardiovascular events, [however] the ARB was superior to the CCB in preventing heart failure, especially in diabetic patients," Dr. Murohara said.

All-cause mortality also was similar. Hospital admission for heart failure was the only outcome measure in which there was a statistically significant difference between the two agents.

In previous nonrandomized analyses comparing ARBs with CCBs, results have been conflicting and, therefore, the preferred first-line class of agents is not well established, Dr. Murohara said. Guidelines mainly recommend ARBs and ACE inhibitors for first-line treatment and reserve CCBs as alternatives or second-line agents, he added.

The NAGOYA-HEART Study is an investigator-initiated trial applying a prospective, randomized open-label, blinded-endpoint (PROBE) method in which allocated treatment was open label but outcomes were adjudicated in a blinded manner as for drug assignment.

The Japanese research team enrolled 1,150 hypertensive patients with either type 2 diabetes (82%) or impaired glucose tolerance (18%) at 46 facilities across the country between 2004 and 2010. Mean glycosylated hemoglobin was 7.0% on the valsartan arm and 6.9% on the amlodipine arm and fasting plasma glucose levels were 8.2 mmol/L and 7.9 mmol/L, respectively. Mean blood pressure was 144/82 mm Hg in each arm.

Patients were randomized to receive either valsartan or amlodipine as their first-line antihypertensive agent. After a run-in phase, patients received valsartan 80 mg/day, titrating to 160 mg/day after 1 week of treatment, or amlodipine 5 mg/day, titrating to 10 mg/day. Both arms could receive other antihypertensives as needed, excluding ACE inhibitors, other ARBs, or CCBs.

The treatment goal was to reduce blood pressure to below 130/80 mm Hg. The primary outcome was a composite of cardiovascular events (acute myocardial infarction, stroke, coronary revascularization, admission due to heart failure, and sudden cardiac death); all-cause mortality was a secondary outcome.

The efficacy and safety analyses included 575 in both the valsartan and amlodipine arms. Patients were followed a median of 3.2 years.

Blood pressure lowering and glucose control were similar between the treatment arms. Blood pressure levels achieved were 131/73 mm Hg with valsartan and 132/74 mm Hg with amlodipine. Final hemoglobin A1C was 6.7% in each arm, Dr. Murohara reported.

There was no difference between the agents in the primary composite cardiovascular outcome. At 3.2 years, cardiovascular events were observed in 54 (9.4%) patients in the valsartan group and 56 (9.7%) in the amlodipine group. "The time-to-event curves showed no difference between the two groups," he said.

Among the components of the composite, only heart failure was affected by treatment, noted in 3 (0.5%) patients on valsartan, compared with 15 (2.6%) on amlodipine, a significant difference. Valsartan use was associated with an 80% relative risk reduction in heart failure admissions.

Safety outcomes were similar, with at least one adverse event reported by 106 patients in the valsartan arm and 112 in the amlodipine arm.

"Our results highlight the safety and efficacy of an ARB, especially in preventing heart failure," he noted, "and support the current recommendations for diabetic hypertensive patients."

Session panelist Dr. Sara Sirna of Temple University, Philadelphia, commented that the NAGOYA-HEART Study is "an excellent study on two drugs we commonly use for patients with diabetes and hypertension, which we see every day in our practices."

She questioned whether there may be a subgroup that would fare better with one versus the other agent. "The ejection fraction was about 40%, mildly reduced, yet those patients seemed to do better on valsartan," she observed.

Dr. Murohara responded that the study did not recruit patients with overt heart failure, but he noted that since the renin-angiotensin system is activated in the setting of heart failure, it makes sense that new-onset heart failure may be prevented better with the ARB.

The study was funded and supported by Nagoya University. Dr. Murohara reported receiving lecturer’s fees from Daiichi-Sankyo, Novartis, Pfizer, and Takeda. Dr. Sirna reported no relevant disclosures.

[Want more news from the ACC's annual scientific session? Check out our complete coverage of the meeting.]

NEW ORLEANS – Prevention of major cardiovascular events was similar in a comparison of valsartan and amlodipine in patients with hypertension and diabetes or glucose intolerance, according to a Japanese study presented April 5 at the annual meeting of the American College of Cardiology.

The Novel Antihypertensive Goal of Hypertension With Diabetes – Hypertensive Events and ARB Treatment (NAGOYA-HEART) Study is the first randomized trial to compare the effects of an angiotensin II receptor blocker (ARB) with a calcium channel blocker (CCB) on cardiovascular outcomes in this patient population. No significant differences were found between the two classes, reported Dr. Toyoaki Murohara of Nagoya (Japan) University.

"Our study showed no difference in the efficacies between the ARB and the CCB in terms of prevention of major cardiovascular events, [however] the ARB was superior to the CCB in preventing heart failure, especially in diabetic patients," Dr. Murohara said.

All-cause mortality also was similar. Hospital admission for heart failure was the only outcome measure in which there was a statistically significant difference between the two agents.

In previous nonrandomized analyses comparing ARBs with CCBs, results have been conflicting and, therefore, the preferred first-line class of agents is not well established, Dr. Murohara said. Guidelines mainly recommend ARBs and ACE inhibitors for first-line treatment and reserve CCBs as alternatives or second-line agents, he added.

The NAGOYA-HEART Study is an investigator-initiated trial applying a prospective, randomized open-label, blinded-endpoint (PROBE) method in which allocated treatment was open label but outcomes were adjudicated in a blinded manner as for drug assignment.

The Japanese research team enrolled 1,150 hypertensive patients with either type 2 diabetes (82%) or impaired glucose tolerance (18%) at 46 facilities across the country between 2004 and 2010. Mean glycosylated hemoglobin was 7.0% on the valsartan arm and 6.9% on the amlodipine arm and fasting plasma glucose levels were 8.2 mmol/L and 7.9 mmol/L, respectively. Mean blood pressure was 144/82 mm Hg in each arm.

Patients were randomized to receive either valsartan or amlodipine as their first-line antihypertensive agent. After a run-in phase, patients received valsartan 80 mg/day, titrating to 160 mg/day after 1 week of treatment, or amlodipine 5 mg/day, titrating to 10 mg/day. Both arms could receive other antihypertensives as needed, excluding ACE inhibitors, other ARBs, or CCBs.

The treatment goal was to reduce blood pressure to below 130/80 mm Hg. The primary outcome was a composite of cardiovascular events (acute myocardial infarction, stroke, coronary revascularization, admission due to heart failure, and sudden cardiac death); all-cause mortality was a secondary outcome.

The efficacy and safety analyses included 575 in both the valsartan and amlodipine arms. Patients were followed a median of 3.2 years.

Blood pressure lowering and glucose control were similar between the treatment arms. Blood pressure levels achieved were 131/73 mm Hg with valsartan and 132/74 mm Hg with amlodipine. Final hemoglobin A1C was 6.7% in each arm, Dr. Murohara reported.

There was no difference between the agents in the primary composite cardiovascular outcome. At 3.2 years, cardiovascular events were observed in 54 (9.4%) patients in the valsartan group and 56 (9.7%) in the amlodipine group. "The time-to-event curves showed no difference between the two groups," he said.

Among the components of the composite, only heart failure was affected by treatment, noted in 3 (0.5%) patients on valsartan, compared with 15 (2.6%) on amlodipine, a significant difference. Valsartan use was associated with an 80% relative risk reduction in heart failure admissions.

Safety outcomes were similar, with at least one adverse event reported by 106 patients in the valsartan arm and 112 in the amlodipine arm.

"Our results highlight the safety and efficacy of an ARB, especially in preventing heart failure," he noted, "and support the current recommendations for diabetic hypertensive patients."

Session panelist Dr. Sara Sirna of Temple University, Philadelphia, commented that the NAGOYA-HEART Study is "an excellent study on two drugs we commonly use for patients with diabetes and hypertension, which we see every day in our practices."

She questioned whether there may be a subgroup that would fare better with one versus the other agent. "The ejection fraction was about 40%, mildly reduced, yet those patients seemed to do better on valsartan," she observed.

Dr. Murohara responded that the study did not recruit patients with overt heart failure, but he noted that since the renin-angiotensin system is activated in the setting of heart failure, it makes sense that new-onset heart failure may be prevented better with the ARB.

The study was funded and supported by Nagoya University. Dr. Murohara reported receiving lecturer’s fees from Daiichi-Sankyo, Novartis, Pfizer, and Takeda. Dr. Sirna reported no relevant disclosures.

[Want more news from the ACC's annual scientific session? Check out our complete coverage of the meeting.]

NEW ORLEANS – Prevention of major cardiovascular events was similar in a comparison of valsartan and amlodipine in patients with hypertension and diabetes or glucose intolerance, according to a Japanese study presented April 5 at the annual meeting of the American College of Cardiology.

The Novel Antihypertensive Goal of Hypertension With Diabetes – Hypertensive Events and ARB Treatment (NAGOYA-HEART) Study is the first randomized trial to compare the effects of an angiotensin II receptor blocker (ARB) with a calcium channel blocker (CCB) on cardiovascular outcomes in this patient population. No significant differences were found between the two classes, reported Dr. Toyoaki Murohara of Nagoya (Japan) University.

"Our study showed no difference in the efficacies between the ARB and the CCB in terms of prevention of major cardiovascular events, [however] the ARB was superior to the CCB in preventing heart failure, especially in diabetic patients," Dr. Murohara said.

All-cause mortality also was similar. Hospital admission for heart failure was the only outcome measure in which there was a statistically significant difference between the two agents.

In previous nonrandomized analyses comparing ARBs with CCBs, results have been conflicting and, therefore, the preferred first-line class of agents is not well established, Dr. Murohara said. Guidelines mainly recommend ARBs and ACE inhibitors for first-line treatment and reserve CCBs as alternatives or second-line agents, he added.

The NAGOYA-HEART Study is an investigator-initiated trial applying a prospective, randomized open-label, blinded-endpoint (PROBE) method in which allocated treatment was open label but outcomes were adjudicated in a blinded manner as for drug assignment.

The Japanese research team enrolled 1,150 hypertensive patients with either type 2 diabetes (82%) or impaired glucose tolerance (18%) at 46 facilities across the country between 2004 and 2010. Mean glycosylated hemoglobin was 7.0% on the valsartan arm and 6.9% on the amlodipine arm and fasting plasma glucose levels were 8.2 mmol/L and 7.9 mmol/L, respectively. Mean blood pressure was 144/82 mm Hg in each arm.

Patients were randomized to receive either valsartan or amlodipine as their first-line antihypertensive agent. After a run-in phase, patients received valsartan 80 mg/day, titrating to 160 mg/day after 1 week of treatment, or amlodipine 5 mg/day, titrating to 10 mg/day. Both arms could receive other antihypertensives as needed, excluding ACE inhibitors, other ARBs, or CCBs.

The treatment goal was to reduce blood pressure to below 130/80 mm Hg. The primary outcome was a composite of cardiovascular events (acute myocardial infarction, stroke, coronary revascularization, admission due to heart failure, and sudden cardiac death); all-cause mortality was a secondary outcome.

The efficacy and safety analyses included 575 in both the valsartan and amlodipine arms. Patients were followed a median of 3.2 years.

Blood pressure lowering and glucose control were similar between the treatment arms. Blood pressure levels achieved were 131/73 mm Hg with valsartan and 132/74 mm Hg with amlodipine. Final hemoglobin A1C was 6.7% in each arm, Dr. Murohara reported.

There was no difference between the agents in the primary composite cardiovascular outcome. At 3.2 years, cardiovascular events were observed in 54 (9.4%) patients in the valsartan group and 56 (9.7%) in the amlodipine group. "The time-to-event curves showed no difference between the two groups," he said.

Among the components of the composite, only heart failure was affected by treatment, noted in 3 (0.5%) patients on valsartan, compared with 15 (2.6%) on amlodipine, a significant difference. Valsartan use was associated with an 80% relative risk reduction in heart failure admissions.

Safety outcomes were similar, with at least one adverse event reported by 106 patients in the valsartan arm and 112 in the amlodipine arm.

"Our results highlight the safety and efficacy of an ARB, especially in preventing heart failure," he noted, "and support the current recommendations for diabetic hypertensive patients."

Session panelist Dr. Sara Sirna of Temple University, Philadelphia, commented that the NAGOYA-HEART Study is "an excellent study on two drugs we commonly use for patients with diabetes and hypertension, which we see every day in our practices."

She questioned whether there may be a subgroup that would fare better with one versus the other agent. "The ejection fraction was about 40%, mildly reduced, yet those patients seemed to do better on valsartan," she observed.

Dr. Murohara responded that the study did not recruit patients with overt heart failure, but he noted that since the renin-angiotensin system is activated in the setting of heart failure, it makes sense that new-onset heart failure may be prevented better with the ARB.

The study was funded and supported by Nagoya University. Dr. Murohara reported receiving lecturer’s fees from Daiichi-Sankyo, Novartis, Pfizer, and Takeda. Dr. Sirna reported no relevant disclosures.

[Want more news from the ACC's annual scientific session? Check out our complete coverage of the meeting.]

NEW ORLEANS – Prevention of major cardiovascular events was similar in a comparison of valsartan and amlodipine in patients with hypertension and diabetes or glucose intolerance, according to a Japanese study presented April 5 at the annual meeting of the American College of Cardiology.

The Novel Antihypertensive Goal of Hypertension With Diabetes – Hypertensive Events and ARB Treatment (NAGOYA-HEART) Study is the first randomized trial to compare the effects of an angiotensin II receptor blocker (ARB) with a calcium channel blocker (CCB) on cardiovascular outcomes in this patient population. No significant differences were found between the two classes, reported Dr. Toyoaki Murohara of Nagoya (Japan) University.

"Our study showed no difference in the efficacies between the ARB and the CCB in terms of prevention of major cardiovascular events, [however] the ARB was superior to the CCB in preventing heart failure, especially in diabetic patients," Dr. Murohara said.

All-cause mortality also was similar. Hospital admission for heart failure was the only outcome measure in which there was a statistically significant difference between the two agents.

In previous nonrandomized analyses comparing ARBs with CCBs, results have been conflicting and, therefore, the preferred first-line class of agents is not well established, Dr. Murohara said. Guidelines mainly recommend ARBs and ACE inhibitors for first-line treatment and reserve CCBs as alternatives or second-line agents, he added.

The NAGOYA-HEART Study is an investigator-initiated trial applying a prospective, randomized open-label, blinded-endpoint (PROBE) method in which allocated treatment was open label but outcomes were adjudicated in a blinded manner as for drug assignment.

The Japanese research team enrolled 1,150 hypertensive patients with either type 2 diabetes (82%) or impaired glucose tolerance (18%) at 46 facilities across the country between 2004 and 2010. Mean glycosylated hemoglobin was 7.0% on the valsartan arm and 6.9% on the amlodipine arm and fasting plasma glucose levels were 8.2 mmol/L and 7.9 mmol/L, respectively. Mean blood pressure was 144/82 mm Hg in each arm.

Patients were randomized to receive either valsartan or amlodipine as their first-line antihypertensive agent. After a run-in phase, patients received valsartan 80 mg/day, titrating to 160 mg/day after 1 week of treatment, or amlodipine 5 mg/day, titrating to 10 mg/day. Both arms could receive other antihypertensives as needed, excluding ACE inhibitors, other ARBs, or CCBs.

The treatment goal was to reduce blood pressure to below 130/80 mm Hg. The primary outcome was a composite of cardiovascular events (acute myocardial infarction, stroke, coronary revascularization, admission due to heart failure, and sudden cardiac death); all-cause mortality was a secondary outcome.

The efficacy and safety analyses included 575 in both the valsartan and amlodipine arms. Patients were followed a median of 3.2 years.

Blood pressure lowering and glucose control were similar between the treatment arms. Blood pressure levels achieved were 131/73 mm Hg with valsartan and 132/74 mm Hg with amlodipine. Final hemoglobin A1C was 6.7% in each arm, Dr. Murohara reported.

There was no difference between the agents in the primary composite cardiovascular outcome. At 3.2 years, cardiovascular events were observed in 54 (9.4%) patients in the valsartan group and 56 (9.7%) in the amlodipine group. "The time-to-event curves showed no difference between the two groups," he said.

Among the components of the composite, only heart failure was affected by treatment, noted in 3 (0.5%) patients on valsartan, compared with 15 (2.6%) on amlodipine, a significant difference. Valsartan use was associated with an 80% relative risk reduction in heart failure admissions.

Safety outcomes were similar, with at least one adverse event reported by 106 patients in the valsartan arm and 112 in the amlodipine arm.

"Our results highlight the safety and efficacy of an ARB, especially in preventing heart failure," he noted, "and support the current recommendations for diabetic hypertensive patients."

Session panelist Dr. Sara Sirna of Temple University, Philadelphia, commented that the NAGOYA-HEART Study is "an excellent study on two drugs we commonly use for patients with diabetes and hypertension, which we see every day in our practices."

She questioned whether there may be a subgroup that would fare better with one versus the other agent. "The ejection fraction was about 40%, mildly reduced, yet those patients seemed to do better on valsartan," she observed.

Dr. Murohara responded that the study did not recruit patients with overt heart failure, but he noted that since the renin-angiotensin system is activated in the setting of heart failure, it makes sense that new-onset heart failure may be prevented better with the ARB.

The study was funded and supported by Nagoya University. Dr. Murohara reported receiving lecturer’s fees from Daiichi-Sankyo, Novartis, Pfizer, and Takeda. Dr. Sirna reported no relevant disclosures.

NEW ORLEANS – Prevention of major cardiovascular events was similar in a comparison of valsartan and amlodipine in patients with hypertension and diabetes or glucose intolerance, according to a Japanese study presented April 5 at the annual meeting of the American College of Cardiology.

The Novel Antihypertensive Goal of Hypertension With Diabetes – Hypertensive Events and ARB Treatment (NAGOYA-HEART) Study is the first randomized trial to compare the effects of an angiotensin II receptor blocker (ARB) with a calcium channel blocker (CCB) on cardiovascular outcomes in this patient population. No significant differences were found between the two classes, reported Dr. Toyoaki Murohara of Nagoya (Japan) University.

"Our study showed no difference in the efficacies between the ARB and the CCB in terms of prevention of major cardiovascular events, [however] the ARB was superior to the CCB in preventing heart failure, especially in diabetic patients," Dr. Murohara said.

All-cause mortality also was similar. Hospital admission for heart failure was the only outcome measure in which there was a statistically significant difference between the two agents.

In previous nonrandomized analyses comparing ARBs with CCBs, results have been conflicting and, therefore, the preferred first-line class of agents is not well established, Dr. Murohara said. Guidelines mainly recommend ARBs and ACE inhibitors for first-line treatment and reserve CCBs as alternatives or second-line agents, he added.

The NAGOYA-HEART Study is an investigator-initiated trial applying a prospective, randomized open-label, blinded-endpoint (PROBE) method in which allocated treatment was open label but outcomes were adjudicated in a blinded manner as for drug assignment.

The Japanese research team enrolled 1,150 hypertensive patients with either type 2 diabetes (82%) or impaired glucose tolerance (18%) at 46 facilities across the country between 2004 and 2010. Mean glycosylated hemoglobin was 7.0% on the valsartan arm and 6.9% on the amlodipine arm and fasting plasma glucose levels were 8.2 mmol/L and 7.9 mmol/L, respectively. Mean blood pressure was 144/82 mm Hg in each arm.

Patients were randomized to receive either valsartan or amlodipine as their first-line antihypertensive agent. After a run-in phase, patients received valsartan 80 mg/day, titrating to 160 mg/day after 1 week of treatment, or amlodipine 5 mg/day, titrating to 10 mg/day. Both arms could receive other antihypertensives as needed, excluding ACE inhibitors, other ARBs, or CCBs.

The treatment goal was to reduce blood pressure to below 130/80 mm Hg. The primary outcome was a composite of cardiovascular events (acute myocardial infarction, stroke, coronary revascularization, admission due to heart failure, and sudden cardiac death); all-cause mortality was a secondary outcome.

The efficacy and safety analyses included 575 in both the valsartan and amlodipine arms. Patients were followed a median of 3.2 years.

Blood pressure lowering and glucose control were similar between the treatment arms. Blood pressure levels achieved were 131/73 mm Hg with valsartan and 132/74 mm Hg with amlodipine. Final hemoglobin A1C was 6.7% in each arm, Dr. Murohara reported.

There was no difference between the agents in the primary composite cardiovascular outcome. At 3.2 years, cardiovascular events were observed in 54 (9.4%) patients in the valsartan group and 56 (9.7%) in the amlodipine group. "The time-to-event curves showed no difference between the two groups," he said.

Among the components of the composite, only heart failure was affected by treatment, noted in 3 (0.5%) patients on valsartan, compared with 15 (2.6%) on amlodipine, a significant difference. Valsartan use was associated with an 80% relative risk reduction in heart failure admissions.

Safety outcomes were similar, with at least one adverse event reported by 106 patients in the valsartan arm and 112 in the amlodipine arm.

"Our results highlight the safety and efficacy of an ARB, especially in preventing heart failure," he noted, "and support the current recommendations for diabetic hypertensive patients."

Session panelist Dr. Sara Sirna of Temple University, Philadelphia, commented that the NAGOYA-HEART Study is "an excellent study on two drugs we commonly use for patients with diabetes and hypertension, which we see every day in our practices."

She questioned whether there may be a subgroup that would fare better with one versus the other agent. "The ejection fraction was about 40%, mildly reduced, yet those patients seemed to do better on valsartan," she observed.

Dr. Murohara responded that the study did not recruit patients with overt heart failure, but he noted that since the renin-angiotensin system is activated in the setting of heart failure, it makes sense that new-onset heart failure may be prevented better with the ARB.

The study was funded and supported by Nagoya University. Dr. Murohara reported receiving lecturer’s fees from Daiichi-Sankyo, Novartis, Pfizer, and Takeda. Dr. Sirna reported no relevant disclosures.

NEW ORLEANS – Prevention of major cardiovascular events was similar in a comparison of valsartan and amlodipine in patients with hypertension and diabetes or glucose intolerance, according to a Japanese study presented April 5 at the annual meeting of the American College of Cardiology.

The Novel Antihypertensive Goal of Hypertension With Diabetes – Hypertensive Events and ARB Treatment (NAGOYA-HEART) Study is the first randomized trial to compare the effects of an angiotensin II receptor blocker (ARB) with a calcium channel blocker (CCB) on cardiovascular outcomes in this patient population. No significant differences were found between the two classes, reported Dr. Toyoaki Murohara of Nagoya (Japan) University.

"Our study showed no difference in the efficacies between the ARB and the CCB in terms of prevention of major cardiovascular events, [however] the ARB was superior to the CCB in preventing heart failure, especially in diabetic patients," Dr. Murohara said.

All-cause mortality also was similar. Hospital admission for heart failure was the only outcome measure in which there was a statistically significant difference between the two agents.

In previous nonrandomized analyses comparing ARBs with CCBs, results have been conflicting and, therefore, the preferred first-line class of agents is not well established, Dr. Murohara said. Guidelines mainly recommend ARBs and ACE inhibitors for first-line treatment and reserve CCBs as alternatives or second-line agents, he added.

The NAGOYA-HEART Study is an investigator-initiated trial applying a prospective, randomized open-label, blinded-endpoint (PROBE) method in which allocated treatment was open label but outcomes were adjudicated in a blinded manner as for drug assignment.

The Japanese research team enrolled 1,150 hypertensive patients with either type 2 diabetes (82%) or impaired glucose tolerance (18%) at 46 facilities across the country between 2004 and 2010. Mean glycosylated hemoglobin was 7.0% on the valsartan arm and 6.9% on the amlodipine arm and fasting plasma glucose levels were 8.2 mmol/L and 7.9 mmol/L, respectively. Mean blood pressure was 144/82 mm Hg in each arm.

Patients were randomized to receive either valsartan or amlodipine as their first-line antihypertensive agent. After a run-in phase, patients received valsartan 80 mg/day, titrating to 160 mg/day after 1 week of treatment, or amlodipine 5 mg/day, titrating to 10 mg/day. Both arms could receive other antihypertensives as needed, excluding ACE inhibitors, other ARBs, or CCBs.

The treatment goal was to reduce blood pressure to below 130/80 mm Hg. The primary outcome was a composite of cardiovascular events (acute myocardial infarction, stroke, coronary revascularization, admission due to heart failure, and sudden cardiac death); all-cause mortality was a secondary outcome.

The efficacy and safety analyses included 575 in both the valsartan and amlodipine arms. Patients were followed a median of 3.2 years.

Blood pressure lowering and glucose control were similar between the treatment arms. Blood pressure levels achieved were 131/73 mm Hg with valsartan and 132/74 mm Hg with amlodipine. Final hemoglobin A1C was 6.7% in each arm, Dr. Murohara reported.

There was no difference between the agents in the primary composite cardiovascular outcome. At 3.2 years, cardiovascular events were observed in 54 (9.4%) patients in the valsartan group and 56 (9.7%) in the amlodipine group. "The time-to-event curves showed no difference between the two groups," he said.

Among the components of the composite, only heart failure was affected by treatment, noted in 3 (0.5%) patients on valsartan, compared with 15 (2.6%) on amlodipine, a significant difference. Valsartan use was associated with an 80% relative risk reduction in heart failure admissions.

Safety outcomes were similar, with at least one adverse event reported by 106 patients in the valsartan arm and 112 in the amlodipine arm.

"Our results highlight the safety and efficacy of an ARB, especially in preventing heart failure," he noted, "and support the current recommendations for diabetic hypertensive patients."

Session panelist Dr. Sara Sirna of Temple University, Philadelphia, commented that the NAGOYA-HEART Study is "an excellent study on two drugs we commonly use for patients with diabetes and hypertension, which we see every day in our practices."

She questioned whether there may be a subgroup that would fare better with one versus the other agent. "The ejection fraction was about 40%, mildly reduced, yet those patients seemed to do better on valsartan," she observed.

Dr. Murohara responded that the study did not recruit patients with overt heart failure, but he noted that since the renin-angiotensin system is activated in the setting of heart failure, it makes sense that new-onset heart failure may be prevented better with the ARB.

The study was funded and supported by Nagoya University. Dr. Murohara reported receiving lecturer’s fees from Daiichi-Sankyo, Novartis, Pfizer, and Takeda. Dr. Sirna reported no relevant disclosures.