Metformin therapy in patients with diabetes mellitus is associated with a 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). Reduced cardiovascular mortality and morbidity have been reported in non-HT patients treated with metformin. Given the high prevalence of type 2 diabetes mellitus (T2DM) in HT patients, we investigated the association between metformin therapy and cardiovascular outcomes after HT. METHODS: The study population comprised 103 DM patients who had undergone HT between 1994 and 2018 and were prospectively followed-up. We excluded from the study patients with type 1 diabetes mellitus. Fifty-five HT patients (53%) in the cohort were treated with metformin. Clinical data were recorded on prospectively designed forms. The primary outcomes included CAV, survival, and the combined end-point of CAV or cardiovascular mortality. RESULTS: 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). Similarly, the combined risk of CAV or cardiovascular mortality was lower in the metformin-treated patients than in those not receiving metformin (32 vs. 68%; log rank p = 0.01). 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 cardiovascular 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 cardiovascular mortality after HT.