CAPOTEN REDUCES MORTALITY 17% IN POST-MI PATIENTS WITHOUT OVERT HEART FAILURE

CAPOTEN REDUCES MORTALITY 17% IN POST-MI PATIENTS WITHOUT OVERT HEART FAILURE, according to results from the multi-center Survival and Ventricular Enlargement (SAVE) trial. Results of the trial, conducted over five years at 45 centers in the U.S. and Canada, were presented by Eugene Braunwald, MD, and Marc Pfeffer, MD, Boston's Brigham and Women's Hospital, on April 14 at the annual meeting of the American College of Cardiology. In the study, 2,231 patients who had experienced a myocardial infarction without symptomatic evidence of heart failure were randomized to either captopril (Bristol-Myers Squibb's Capoten) or placebo. Patients averaged 60 years of age and had left ventricular enlargement indicated by an average ejection fraction of 31%. Treatment began three to 16 days post-myocardial infarction, with patients titrated to a captopril dose of 150 mg (50 t.i.d.) per day. Of the 502 patients who died in the study, 274 (24.6%) had received placebo compared to 228 (20.6%) treated with captopril, a 17% reduction in mortality. Patients receiving captopril also had a 19% reduction in cardiovascular death. Second myocardial infarctions were reduced by 24% with captopril therapy and progression to heart failure requiring open- label use of other ACE inhibitors was reduced by 36%. Preliminary analysis of the data indicated that captopril also lessened the severity of second heart attacks. Captopril therapy benefited patients whether or not they had received thrombolytic therapy, Braunwald said. Thirty-three percent of all patients received thrombolytic therapy in the study and 35% were treated with beta blockers. The researchers estimated that 12,000-15,000 lives could be saved each year through long-term captopril use. That number is based on the estimate that 600,000 patients are released from the hospital annually following a myocardial infarction and that 40%- 60% of those would be eligible for captopril therapy, yielding a new pool of 250,000 patients every year. Patients would have to take captopril over an extended period since benefit from the therapy only appeared after 10 months of use. Braunwald touted the SAVE results as providing a rationale for long-term captopril treatment of post-MI patients with ventricular enlargement. The indication would be a new use for captopril. He added that it might be "logical to extrapolate [the findings] to patients who didn't have a heart attack and who have some other form of heart disease [and] who show impaired [left ventricular function]." Braunwald declined to speculate whether other ACE inhibitors might have the same beneficial effect as captopril in a post-MI, pre-heart failure population. "We have no information whether this is an [ACE inhibitor] class effect," he said. New analyses from the Studies of Left Ventricular Dysfunction (SOLVD) trial, also presented at the ACC meeting, support broader use of ACE inhibitors in patients with heart failure. The analyses found that all subgroups of the SOLVD patient population benefited equally from treatment with enalapril (Merck's Vasotec). Previously reported results from SOLVD showed a 16% reduction in mortality and a 25% reduction in hospitalizations for patients with coronary heart failure. In addition, a new look at the data found a 23% decrease in myocardial infarctions. Observing that the SOLVD data "fits absolutely with the SAVE data," National Heart Lung and Blood Institute researcher Salim Yusuf, a SOLVD investigator, said that "we now have a new reason to use ACE inhibitors not only to improve survival and to prevent worsening heart failure and hospitalizations for those reasons but also to prevent new ischemic events." Addressing whether the effects seen in SOLVD and SAVE are a class effect, Yusuf said: "I would be happy to use any ACE inhibitor that has been shown to have a reasonably powerful effect at decent doses." While acknowledging that there seems to be class effect, SOLVD researcher Bertram Pitt, MD, University of Michigan, said that he would not recommend newer ACE inhibitors over enalapril or captopril until effective dosing for those agents has been determined for these populations.