A RANDOMIZED CONTROLLED TRIAL OF EPOPROSTENOL THERAPY FOR SEVERE CONGESTIVE-HEART-FAILURE - THE FLOLAN INTERNATIONAL RANDOMIZED SURVIVAL TRIAL (FIRST)

This trial evaluated the effects of epoprostenol on patients with seve re left ventricular failure. Patients with class IIIB/IV congestive he art Failure and decreased left ventricular ejection fraction were elig ible for enrollment if angiography documented severely compromised hem odynamics while the patient was receiving a regimen of digoxin, diuret ics, and an angiotensin-converting enzyme inhibitor. We randomly assig ned 471 patients to epoprostenol infusion or standard care. The primar y end point was survival; secondary end points were clinical events, c ongestive heart failure symptoms, distance walked in 6 minutes, and qu ality-of-life measures. The median dose of epoprostenol was 4.0 ng/kg/ min, resulting in a significant increase in cardiac index (1.81 to 2.6 1 L/min/m(2)), a decrease in pulmonary capillary wedge pressure (24.5 to 20.0 mm Hg), and a decrease in systemic vascular resistance (20.76 to 12.33 units). The trial was terminated early because of a strong tr end toward decreased survival in the patients treated with epoprosteno l. Chronic intravenous epoprostenol therapy is not associated with imp rovement in distance walked, quality of life, or morbid events and is associated with an increased risk of death.