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

Abstract

Purpose 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. Conclusion 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.