Erectile dysfunction, phosphodiesterase-5 inhibitor use and risk of cardiovascular disease and mortality in people with diabetes: A systematic review and meta-analysis

Background: Phosphodiesterase-5 inhibitors (PDE5-Is), used in the management of erectile dysfunction (ED), have potential cardioprotective benefits. The impact of PDE5-Is on reducing adverse cardiovascular outcomes in pa-tients with diabetes mellitus (DM) and ED is uncertain. Using a systematic review and meta-analysis of obser-vational cohort studies and randomised controlled trials (RCTs), we evaluated if (i) the association of PDE5-Is in people with ED and DM and their risk of cardiovascular disease (CVD) and mortality and (ii) ED confers an excess risk of CVD and mortality in patients with DM compared with no DM.Methods: Studies were identified from MEDLINE, Embase, the Cochrane Library, Web of Science citation search and search of bibliographies to April 2022. Study-specific risk ratios (RRs) with 95% confidence intervals (CIs) were pooled.Results: Eighteen unique studies reported on the cardiovascular impact of ED in patients with and without DM. In the general population, the RRs (95% CIs) of ED for composite CVD/MACE, all-cause mortality, CHD and stroke were 1.43 (1.31-1.55), 1.47 (1.31-1.65), 1.59 (1.39-1.82), and 1.34 (1.15-1.56), respectively. The respective estimates were 1.68 (1.15-2.45), 1.40 (0.90-2.18), 1.41 (1.24-1.61) and 1.32 (1.09-1.60) in the diabetes population. Interaction analyses suggested similar risk in both populations. Six studies reported the cardiovas-cular effects of PDE5-Is in people with ED and DM. Limited RCT data showed no significant differences in the risk of major adverse cardiac event (MACE), coronary heart disease (CHD) and all-cause mortality comparing PDE5-I use with non-use: RRs (95% CIs) of 3.47 (0.17-69.19), 1.31 (0.10-16.54) and 0.35 (0.12-1.05), respectively.Conclusions: ED confers no excess risk of CVD and mortality in patients with DM compared with no DM. Limited and inadequately powered data shows no significant differences in the risk of adverse cardiovascular outcomes comparing use of PDE5-Is with non-use in patients with ED and DM. PROSPERO Registration: CRD42022324537