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Vesnarinone Reduces Symptoms but Increases Mortality

Vesnarinone is a positive inotropic drug that is thought to improve muscle contractility through ion-channel effects that augment sodium-calcium exchange. In a previous study of 577 patients with class III or IV heart failure, six months of treatment with 60 mg of vesnarinone was associated with a significant reduction in mortality and major cardiovascular morbidity. This manufacturer-supported, multicenter trial randomized 3,833 patients with class III or IV heart failure and systolic dysfunction to 30 or 60 mg of vesnarinone or placebo.

At a mean follow-up of 41 weeks, the mortality rate was significantly lower in the placebo group than in the 60-mg vesnarinone group (18.9 percent vs. 22.9 percent, respectively). A 21 percent mortality rate in the 30-mg group was not statistically significant. The increased mortality in the vesnarinone groups was attributed to an increase in sudden death from cardiac causes. Hospital admissions for heart failure were similar among the groups. Quality of life improved for all three groups, with a significantly greater improvement occurring in the 60-mg group compared with the placebo group at 8 and 16 weeks, but not at 26 weeks.

Comment: Although this trial of vesnarinone is consistent with previous studies of other inotropic agents (e.g., milrinone and flosequinan) in showing increased mortality associated with the therapy, quality of life improved with a 60-mg dose. Rather than disregard this therapy, the authors and an editorialist suggest that some patients may be willing to increase their risk of dying in order to feel better in the time that remains to them.

— HM Krumholz

Published in Journal Watch Cardiology January 22, 1999

Citation(s):

Cohn JN et al for the Vesnarinone Investigators. A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. N Engl J Med 1998 Dec 17 339 1810-1816.

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Stevenson LW. Inotropic therapy for heart failure. N Engl J Med 1998 Dec 17 339 1848-1850.

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• Medline abstract (Free)