Effects of vesnarinone on morbidity and mortality in patients with heart failure. Vesnarinone Study Group

N Engl J Med. 1993 Jul 15;329(3):149-55. doi: 10.1056/NEJM199307153290301.


Background: Inotropic therapy, other than with digitalis glycosides, has had limited success in patients with chronic congestive heart failure. We investigated whether vesnarinone, a new positive inotropic agent, 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-converting-enzyme inhibitor (90 percent) who had ejection fractions of 30 percent or less were randomly assigned to receive double-blinded therapy with 60 mg of vesnarinone per day, 120 mg of vesnarinone per day, or placebo. Afer 253 patients had been enrolled, randomization to the 120-mg vesnarinone group had to be stopped because of a significant increase in early mortality in this group. Thereafter, patients were randomly assigned only to 60 mg of vesnarinone per day (a total of 239 patients) or placebo (a total of 238 patients).

Results: Significantly fewer patients in the group receiving 60 mg of vesnarinone than in the group receiving placebo (26 vs. 50 patients; P = 0.003) died or had worsening heart failure during the six-month study period. The reduction in risk was 50 percent (95 percent confidence interval, 20 to 69 percent). Similarly, there was a 62 percent reduction (95 percent confidence interval, 28 to 80 percent) in the risk of dying from any cause among the patients receiving vesnarinone. Furthermore, quality of life improved 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 percent of the patients.

Conclusions: Six months of therapy with 60 mg of vesnarinone per day resulted in lower morbidity and mortality and improved the quality of life of patients with congestive heart failure. However, a higher dose of vesnarinone (120 mg per day) increased mortality, suggesting that this drug has a narrow therapeutic range; the long-term effects of vesnarinone are unknown.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cardiotonic Agents / administration & dosage
  • Cardiotonic Agents / therapeutic use*
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Heart Failure / drug therapy*
  • Heart Failure / epidemiology
  • Heart Failure / mortality*
  • Humans
  • Male
  • Middle Aged
  • Morbidity
  • Proportional Hazards Models
  • Prospective Studies
  • Pyrazines
  • Quality of Life
  • Quinolines / administration & dosage
  • Quinolines / therapeutic use*


  • Cardiotonic Agents
  • Pyrazines
  • Quinolines
  • vesnarinone