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 severe left ventricular failure. Patients with class IIIB/IV congestive heart failure and decreased left ventricular ejection fraction were eligible for enrollment if angiography documented severely compromised hemodynamics while the patient was receiving a regimen of digoxin, diuretics, and an angiotensin-converting enzyme inhibitor. We randomly assigned 471 patients to epoprostenol infusion or standard care. The primary end point was survival; secondary end points were clinical events, congestive heart failure symptoms, distance walked in 6 minutes, and quality-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 2.61 L/min/m2), 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 trend toward decreased survival in the patients treated with epoprostenol. Chronic intravenous epoprostenol therapy is not associated with improvement in distance walked, quality of life, or morbid events and is associated with an increased risk of death.
Califf
R M
RM
Duke University Medical Center, Durham, NC, USA.
Adams
K F
KF
McKenna
W J
WJ
Gheorghiade
M
M
Uretsky
B F
BF
McNulty
S E
SE
Darius
H
H
Schulman
K
K
Zannad
F
F
Handberg-Thurmond
E
E
Harrell
F E
FE
Wheeler
W
W
Soler-Soler
J
J
Swedberg
K
K
D000368:Aged; D000792:Angiography; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000627:therapeutic use; D002423:Cause of Death; D004077:Digoxin / Q000627:therapeutic use; D004232:Diuretics / Q000627:therapeutic use; D011464:Epoprostenol / Q000008:administration & dosage / Q000627:therapeutic use*; D017079:Exercise Tolerance / Q000187:drug effects; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D011788:Quality of Life; D012307:Risk Factors; D013318:Stroke Volume / Q000187:drug effects; D015996:Survival Rate; D014655:Vascular Resistance / Q000187:drug effects; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy; D016138:Walking / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002316:Cardiotonic Agents; D004232:Diuretics; D004077:Digoxin; D011464:Epoprostenol