Gender Differences in Survival in Advanced Heart Failure Insights From the FIRST Study

Background—Previous natural history studies in broad populations of heart failure patients have associated female gender with improved survival, particularly in patients with a nonischemic etiology of ventricular dysfunction. This study investigates whether a similar survival advantage for women would be evident among patients with advanced heart failure. Methods and Results—The study analysis is based on the Flolan International Randomized Survival Trial (FIRST) study which enrolled 471 patients (359 men and 112 women) who had evidence of end-stage heart failure with marked symptoms (60 % NYHA class IV) and severe left ventricular dysfunction (left ventricular ejection fraction 1864.9%). A Cox proportional-hazards model, adjusted for age, gender, 6-minute walk, dobutamine use at randomization, mean pulmonary artery blood pressure, and treatment assignment, showed a significant association between female gender and better survival (relative risk of death for men versus women was 2.18, 95 % CI 1.39 to 3.41; P,0.001). Although formal interaction testing was negative (P50.275), among patients with a nonischemic etiology of heart failure, the relative risk of death for men versus women was 3.08 (95 % CI 1.56 to 6.09, P50.001), whereas among those with ischemic heart disease, the relative risk of death for men versus women was 1.64 (95 % CI 0.87 to 3.09, P50.127). Conclusions—Women with advanced heart failure appear to have better survival than men. Subgroup analysis suggests this finding is strongest among patients with a nonischemic etiology of heart failure. (Circulation. 1999;99:1816-1821.