Effects of Vesnarinone on Morbidity and Mortality in Patients with Heart Failure
Arthur M. Feldman, Michael R. Bristow, William W. Parmley, Peter E. Carson, Carl J. Pepine, Edward M. Gilbert, John E. Strobeck, Grady H. Hendrix, Eric R. Powers, Raymond P. Bain, B.G. White, for The Vesnarinone Study Group
Background Inotropic therapy, other than with digitalis glycosides,has had limited success in patients with chronic congestiveheart failure. We investigated whether vesnarinone, a new positiveinotropic agent, reduces morbidity and mortality and improvesthe quality of life of patients with symptomatic heart failure.
Methods Patients receiving concomitant therapy with digoxin(87 percent) and an angiotensin-converting-enzyme inhibitor(90 percent) who had ejection fractions of 30 percent or lesswere randomly assigned to receive double-blinded therapy with60 mg of vesnarinone per day, 120 mg of vesnarinone per day,or placebo. After 253 patients had been enrolled, randomizationto the 120-mg vesnarinone group had to be stopped because ofa significant increase in early mortality in this group. Thereafter,patients were randomly assigned only to 60 mg of vesnarinoneper day (a total of 239 patients) or placebo (a total of 238patients).
Results Significantly fewer patients in the group receiving60 mg of vesnarinone than in the group receiving placebo (26vs. 50 patients; P = 0.003) died or had worsening heart failureduring the six-month study period. The reduction in risk was50 percent (95 percent confidence interval, 20 to 69 percent).Similarly, there was a 62 percent reduction (95 percent confidenceinterval, 28 to 80 percent) in the risk of dying from any causeamong the patients receiving vesnarinone. Furthermore, qualityof life improved to a greater extent in the vesnarinone groupthan in the placebo group over 12 weeks (P = 0.008). The principalside effect associated with vesnarinone was reversible neutropenia,which occurred in 2.5 percent of the patients.
Conclusions Six months of therapy with 60 mg of vesnarinoneper day resulted in lower morbidity and mortality and improvedthe quality of life of patients with congestive heart failure.However, a higher dose of vesnarinone (120 mg per day) increasedmortality, suggesting that this drug has a narrow therapeuticrange; the long-term effects of vesnarinone are unknown.
Source Information
The members of the Vesnarinone Study Group are listed in the Appendix.
Address reprint requests to Dr. Feldman at the Peter Belfer Cardiac Laboratories, Department of Medicine, Johns Hopkins University School of Medicine, Richard S. Ross Research Bldg., Rm. 835, 720 Rutland Ave., Baltimore, MD 21205.
Vesnarinone for Heart Failure
Swedberg K., Wedel H., Neely D., Schwartz A., Feldman A. M., Bristow M. R., Parmley W. W., Packer M.
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N Engl J Med 1994;
330:64-66, Jan 6, 1994.
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