Effect of phosphodiesterase inhibitors on survival of patients with chronic congestive heart failure

Milton Packer

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Abstract

Controlled and uncontrolled hemodynamic and clinical studies have noted that the long-term treatment of patients with chronic heart failure with phosphodiesterase (PDE) inhibitors, such as amrinone, milrinone, enoximone and imazodan, may accelerate progression of the underlying disease and provoke serious ventricular arrhythmias. However, in an experimental model of chronic progressive left ventricular dysfunction, milrinone has been reported to reduce mortality to a degree comparable to that seen with the converting-enzyme inhibitors. These discordant observations suggest that either the deleterious hemodynamic and electrophysiologic effects of the PDE inhibitors are not translated into an adverse effect on mortality, or the animal model used to evaluate the effects of milrinone cannot be used to investigate the action of these drugs in human heart failure. Unfortunately, no trial has prospectively evaluated the effect of PDE inhibition on the survival of patients with heart failure. To address this need, the Prospective Randomized Milrinone Survival Evaluation (PROMISE Trial) has been launched in 75 to 90 clinical research centers in the United States and Canada. This study will enroll 750 patients with severe (class IV) heart failure, who have symptoms refractory to conventional therapy with digitalis, diuretics, converting-enzyme inhibitors and direct-acting vasodilators. Patients will be randomly assigned to additional treatment with either oral milrinone or placebo, and followed until death or to the conclusion of the study. The primary end point will be all-cause mortality, but the effect of milrinone on functional capacity will also be evaluated. The results of the study should define the place of PDE inhibitors in the treatment of chronic heart failure.

Original languageEnglish (US)
Pages (from-to)A41-A45
JournalThe American journal of cardiology
Volume63
Issue number2
DOIs
StatePublished - Jan 3 1989

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ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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