A Dose-Dependent Increase in Mortality with Vesnarinone among Patients with Severe Heart Failure

The search for a positive inotropic drug that could relieve symptoms and improve the prognosis in patients with heart failure who were already being treated with angiotensin-converting–enzyme (ACE) inhibitors led to the development of vesnarinone, a drug with multiple mechanisms that appears to enhance contractility through ion-channel effects that augment sodium–calcium exchange. 1 – 3 Short-term administration of vesnarinone to patients with heart failure was associated with limited and variable hemodynamic effects, 4 – 6 but small placebo-controlled trials showed a favorable effect on the quality of life and morbidity. 7 , 8 In a multicenter study initiated in 1990, 577 patients with New York Heart . . .