Long-term oral therapy of congestive heart failure with phosphodiesterase inhibitors

The existing management of severe chronic congestive heart failure carries a dismal prognosis. Mortality over 6 months is 50% by some estimates. This fact, coupled with increasing concern for the safety and efficacy of the digitalis glycosides, has stimulated an intense search for new oral cardiotonic agents suitable for chronic administration. Despite the ability of many phosphodiesterase inhibiting agents to affect profound hemodynamic improvements acutely after oral or intravenous administration, none of the four agents here reviewed in 30 clinical trials has been adequately proven to provide benefit over conventional long-term therapy of severe heart failure. The four drugs to have undergone long-term clinical trials are amrinone, milrinone, enoximone (MDL 17043), and piroximone (MDL 19,025). For amrinone, inefficacy was revealed through carefully designed, placebo-controlled studies despite initial enthusiasm generated by open uncontrolled trials. Enoximone has suffered rapid attenuation of its hemodynamic effectiveness in most studies, and piroximone failed in its only long-term trial. Therefore, final judgment on most of these agents must await completion of controlled clinical trials, and any initial optimism stimulated by the current uncontrolled studies should be met with reservation.