EFFECTS OF VESNARINONE ON MORBIDITY AND MORTALITY IN PATIENTS WITH HEART-FAILURE

Background. Inotropic therapy, other than with digitalis glycosides, h as had limited success in patients with chronic congestive heart failu re. We investigated whether vesnarinone, a new positive inotropic agen t, reduces morbidity and mortality and improves the quality of life of patients with symptomatic heart failure. Methods. Patients receiving concomitant therapy with digoxin (87 percent) and an angiotensin-conve rting-enzyme inhibitor (90 percent) who had ejection fractions of 30 p ercent or less were randomly assigned to receive double-blinded therap y with 60 mg of vesnarinone per day, 120 mg of vesnarinone per day, or placebo. After 253 patients had been enrolled, randomization to the 1 20-mg vesnarinone group had to be stopped because of a significant inc rease in early mortality in this group. Thereafter, patients were rand omly assigned only to 60 mg of vesnarinone per day (a total of 239 pat ients) or placebo (a total of 238 patients). Results. Significantly fe wer patients in the group receiving 60 mg of vesnarinone than in the g roup receiving placebo (26 vs. 50 patients; P = 0.003) died or had wor sening heart failure during the six-month study period. The reduction in risk was 50 percent (95 percent confidence interval, 20 to 69 perce nt). Similarly, there was a 62 percent reduction (95 percent confidenc e interval, 28 to 80 percent) in the risk of dying from any cause amon g the patients receiving vesnarinone. Furthermore, quality of life imp roved to a greater extent in the vesnarinone group than in the placebo group over 12 weeks (P = 0.008). The principal side effect associated with vesnarinone was reversible neutropenia, which occurred in 2.5 pe rcent of the patients. Conclusions. Six months of therapy with 60 mg o f vesnarinone per day resulted in lower morbidity and mortality and im proved the quality of life of patients with congestive heart failure. However, a higher dose of vesnarinone (120 mg per day) increased morta lity, suggesting that this drug has a narrow therapeutic range; the lo ng-term effects of vesnarinone are unknown.