BRISTOL’s CAPOTEN REDUCES SUDDEN DEATH BY 20% IN ASYMPTOMATIC HEART FAILURE

BRISTOL's CAPOTEN REDUCES SUDDEN DEATH BY 20% IN ASYMPTOMATIC HEART FAILURE patients, according to new data from the SAVE trial, study investigator Milton Packer, MD, Columbia University, said at a Nov. 18 press conference during the American Heart Association's 65th Scientific Sessions in New Orleans. Further analysis of the Survival and Ventricular Enlargement trial showed "a 20% reduction in sudden death...that mirrored and paralleled in a striking fashion the [19%] reduction in all cause mortality" previously reported from SAVE, Packer said. Published in the Sept. 1 New England Journal of Medicine, the SAVE trial evaluated the effect of Bristol-Myers Squibb's ACE inhibitor Capoten (captopril) on mortality in 2,231 patients with left ventricular dysfunction following a myocardial infarction ("The Pink Sheet" Sept. 7, T&G-6). "The reason that we thought that this particular finding was quite important was the fact that many physicians have been reluctant to use ACE inhibitors in patients with no symptoms or mild symptoms because they believe that most of the benefits of ACE inhibitors occur after the disease becomes more progressive," Packer stated. "In fact, if physicians intervene early with ACE inhibitors they will have a reduction in death even when symptoms have not progressed to the final stages of the disease," Packer said. Packer noted that the reduction in sudden death seen with SAVE was the "one difference in the findings" of the SAVE and the Studies of Left Ventricular Dysfunction (SOLVD), which compared Merck's ACE inhibitor Vasotec (enalapril) with placebo in 6,797 patients with symptomatic and asymptomatic heart failure. The final results of the SOLVD trial also were published in the Sept. 1 New England Journal of Medicine. "The SOLVD trial reported that all of the reduction in mortality resulted from a reduction in death from progressive heart failure with no effect on sudden death," Packer said. Explaining that heart failure patients with left ventricular dysfunction either die of pump failure, from recurrent myocardial infarction, or suddenly (possibly from ventricular arrhythmia), Packer noted that both SAVE and SOLVD show that the two ACE inhibitors reduce deaths from pump failure and from recurrent MI but that SAVE also showed that captopril reduces sudden death. Packer noted that "the overall results of the SAVE trial are very parallel in fact in a very striking fashion to the SOLVD trial." New results from SOLVD were presented at the press conference by one of the investigators, Salim Yusuf, MD, Hamilton General Hospital, Hamilton, Ontario. Yusuf reported that data from SOLVD showed the unexpected result that enalapril causes a reduction in myocardial infarction and unstable angina. Yusuf explained that in both arms of the SOLVD trial (symptomatic and asymptomatic patients with low ejection fraction), "we had about a 20-to-22% reduction in myocardial infarction and unstable angina." These were statistically significant results, he added. Summarizing the results from the two arms of the SOLVD trial, Yusuf said: "It's an extraordinarily clear result that ACE inhibitors do benefit patients with low ejection fraction" regardless of whether they have symptomatic heart failure. At the AHA meeting, a SOLVD study investigator presented results from radionuclide ventriculograms done in 108 asymptomatic patients in comparison with 55 symptomatic patients. According to an abstract of the analysis, asymptomatic patients show less left ventricular dilatation and "therefore derive less benefit from ACE inhibition" than symptomatic patients. "However, after three years, significant enalapril effect is detected, with reduced left ventricular volumes and prevention of LV dilatation by ACE inhibition."