Effect of oral milrinone on mortality in severe chronic heart failure

Positive inotropic drugs, such as milrinone, enhance the heart's contractile ability. These drugs work by altering various physiological mechanisms, but their long-term effectiveness and safety for people suffering from chronic heart failure has not been determined. To learn more about this issue, a study of mortality among patients with severe chronic heart failure was carried out at 119 medical centers in the US and Canada. The subjects were randomly assigned to receive either oral milrinone (561 patients) or a placebo drug (527 patients) in additional to their regular drug regimens. They were reevaluated every one to three months and dosage adjustments for all drugs were made as needed. The study began on January 24, 1989 and was stopped five months before its scheduled completion, on October 4, 1990. This decision was based on the adverse effect on survival among patients receiving milrinone. Thirty percent (168 patients) of the milrinone group died, compared with 24 percent (127 patients) of the placebo group. Milrinone was associated with a 34 percent increase in cardiovascular mortality and a 28 percent increase in death due to all causes. When patients were further subdivided according to such variables as the cause of heart failure, blood sodium levels, age, or presence of angina, milrinone was found to have adverse effects on all subgroups. No signs were seen of a beneficial effect of the drug on symptoms or functional capacity. The poor effects of the drug are at variance with laboratory results using laboratory animals, where milrinone improved both performance and survival. Milrinone works by enhancing cyclic AMP in the heart; in light of these and related results, it is likely that a decline in levels of myocardial cyclic AMP has adaptive value in chronic heart failure. (Consumer Summary produced by Reliance Medical Information, Inc.)