Long-term effect of folic acid therapy in heart transplant recipients: follow-up analysis of a randomized study.

Background. Folic acid therapy reduces homocysteine plasma levels, which seem to influence occurrence of cardiac allograft vasculopathy, but its effect on medium- or long-term prognosis after heart transplantation is unknown. Methods. We analyzed 7-year outcome of 51 recipients randomized to receive 15 mg/day of methyltertrahydrofolate for I year after heart transplantation or standard therapy alone (originally, for intravascular ultrasound study of short-term cardiac allograft vasculopathy progression); recipients were observed for a further 5 to 6 years. Results. Overall, 13 deaths occurred (six oncologic, five cardiovascular, two infective). Estimated 7-year survival was better in recipients randomized to folate (88% +/- 6% vs. 61% +/- 9%, P=0.04). After adjusting for age, pretransplant coronary artery disease, and hyperhomocysteinernia, posttransplant folic acid therapy was associated with lower mortality (relative risk [RR] 0.53, 95% confidence interval [CI] 0.25-0.97; P=0.036), apparently driven by reductions in both cancer-related and cardiovascular causes. Reduced mortality was marked in a high-risk subgroup comprising older recipients and patients transplanted because of coronary artery disease (RR 0.43,95% CI 0.17-0.85) but not in the lower-risk subgroup (RR 1.11, 95% CI 0.22-5.61).