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 1 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 hyperhomocysteinemia, 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).


CONCLUSIONS
Although further studies are needed, it seems reasonable to suggest folate therapy to heart transplant recipients. It is possible that properties other than homocysteine reduction may provide antitumoral benefits.
Potena
Luciano
L
Institute of Cardiovascular Diseases, Alma Mater Studiorum University of Bologna, Bologna, Italy. luciano.potena2@unibo.it
Grigioni
Francesco
F
Masetti
Marco
M
Magnani
Gaia
G
Coccolo
Fabio
F
Fallani
Francesco
F
Russo
Antonio
A
Pizzuti
Manuela
M
Scalone
Antonella
A
Bianchi
Isidoro G
IG
Branzi
Angelo
A
D000328:Adult; D000368:Aged; D002423:Cause of Death; D005492:Folic Acid / Q000627:therapeutic use*; D005500:Follow-Up Studies; D016027:Heart Transplantation / Q000009:adverse effects / Q000401:mortality; D006801:Humans; D008875:Middle Aged; D014184:Transplantation, Homologous; D014652:Vascular Diseases / Q000517:prevention & control
D005492:Folic Acid