Metformin Therapy is Associated with Reduced Risk of Vasculopathy and Cardiovascular Mortality after Heart Transplantation

Background: Cardiac allograft vasculopathy (CAV) is a major cause of morbidity and mortality following heart transplantation (HT). Lower cardiovascular (CV) mortality and morbidity have been reported in non-HT patients treated with metformin. Given the high prevalence of diabetes mellitus (DM) in HT patients, we investigated the association between metformin therapy and CV outcomes after HT.

Methods: The study population comprised 103 DM patients who had undergone HT between 1994 and 2018 and were prospectively followed-up. Clinical data were recorded on prospectively designed forms. The primary outcomes included CAV and the combined end-point of CAV or CV mortality. Treatment with metformin and the development of CAV or the combined end-point of CAV or CV mortality were assessed as time-dependent factors in the analyses.

Results: Fifty-five HT patients (53%) were treated with metformin whereas 48 (47%) patients were not. Kaplan-Meier survival analysis showed that the CAV rate at 20 years of follow-up was lower in DM patients treated with metformin than in those who were not (30% vs. 65%; log-rank p=0.044; Figure); similarly, the combined risk of CAV or CV mortality was lower in the metformin-treated patients (32% vs. 68%; log rank p=0.01; Figure). Consistently, multivariate analysis adjusted for age and comorbidities showed that metformin therapy was independently associated with a significant 90% reduction (95% confidence interval 0.02-0.46, p=0.003) in the risk for the development of CAV, and a 91% reduction (95% confidence interval 0.02-0.42; p=0.003) in the risk for CAV or CV mortality.

Conclusions: In diabetic HT patients, metformin therapy is independently associated with a significant reduction in the long-term risk for CAV and the combined end-point of CAV or CV mortality after HT.