Enoximone (MDL 17,043), a phosphodiesterase inhibitor, in the treatment of advanced, unstable chronic heart failure

Abstract

Patients with advanced heart failure may be candidates for mechanical circulatory support, heart transplantation, or both. Optimal medical therapy in such patients, who are frequently unstable clinically, is focused on traditional and newer methods of inotropic support. Accordingly, the response to intravenous and oral enoximone, an experimental compound with phosphodiesterase inhibitory properties, was examined in 25 patients with unstable, severe chronic heart failure as a result of ischemic or myopathic heart disease. Eight hospitalized patients had far-advanced failure and were dependent on dobutamine, dopamine, or both to support their cardiocirculatory status (group 1). Seventeen patients had severe failure and were hospitalized electively because of their clinical instability despite digoxin, diuretics, and vasodilators (group 2). Intravenous (1 to 2 mg/kg) and oral (1 to 2 mg/kg) enoximone significantly (p less than 0.05) improved right and left heart function, and the salutory hemodynamic response was sustained for 6 to 8 hours. In group 1, catecholamines were discontinued and clinical stability was reestablished on oral enoximone; stability was also restored in group 2. Nevertheless, 19 patients died on long-term enoximone therapy with approximately half succumbing to their heart failure. Thus enoximone, a compound with inotropic and vasodilator properties, was useful in the acute and short-term management of unstable, chronic heart failure and had an additive hemodynamic benefit to dobutamine, dopamine, or both. Enoximone may therefore be a useful adjunct to stabilizing these patients before mechanical circulatory support or transplantation. The advanced degree of myocardial failure in these patients, however, precludes enoximone together with standard medical therapy from having a more favorable impact on clinical outcome in these patients.