Long-term effects of phosphodiesterase-5 inhibitors on cardiovascular outcomes and death: a systematic review and meta-analysis of cohort studies

Abstract

Abstract Background Phosphodiesterase type 5 inhibitors (PDE-5i), which are widely used for the treatment of erectile dysfunction, have been found to exhibit systemic vascular benefits by improving endothelial function possibly lowering the risk for cardiovascular events and death. Purpose We sought to evaluate the effects of PDE5i on long-term cardiovascular outcomes and mortality. Methods A comprehensive search of electronic databases was conducted up to February 28, 2022. Cohort studies comparing PDE5i treatment at any dose with placebo or no treatment and a minimum follow-up duration of 6 months were considered eligible. The outcomes of interest were: (1) major adverse cardiovascular events (MACE) and (2) all-cause mortality. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated. Results Eight trials were included (1,152,106 subjects, 8.5% treated with PDE5i). All were males [median age 61.5 years (range 30–72.8)]. The median follow-up duration was 3.8 years (range 2.3–7.5) across the studies. PDE5i use was associated with significant reduction in the composite of MACE [RR 0.79, 95% confidence intervals (CI) 0.69–0.91] (Figure 1). In addition, the analysis of pooled data from 5 studies, after removal of a study with a relatively small sample size, demonstrated that the use of PDE5i was associated with a significantly lower risk of all-cause mortality (RR 0.70, 95% CI 0.53–0.91) (Figure 2). Focusing on patients with a history of coronary artery disease, PDE5i was also found to reduce the risk of all-cause mortality by 15% (RR 0.85, 95% CI 0.74–0.98). Conclusion The use of PDE5i in men with or without known coronary artery disease was associated with a lower risk of cardiovascular events and overall mortality. This information underlines that PDE5i could provide considerable clinical benefit beyond the treatment of ED and could instigate the conduction of further, large-scale randomized clinical trials. Funding Acknowledgement Type of funding sources: None.