The role of tadalafil and sildenafil in reducing the risk of cardiovascular outcomes

M.V. Leonova

Interregional public organization Association of Clinical Pharmacologists (Moscow branch), Moscow, Russia

Sildenafil and tadalafil are selective PDE5 inhibitors for the treatment of erectile dysfunction (ED) that have vasodilatory properties mediated through NO and cGMP via smooth muscle relaxation. PDE5 inhibitors are approved for the treatment of ED, but only tadalafil is approved for lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia. The association between ED, LUTS, and cardiovascular disease (CVD) has been established. Due to the expression of PDE5 in the cardiovascular system, potential mechanisms of PDE5 inhibitors include improvement of endothelial function, vasodilation with modest reductions in BP and afterload, direct myocardial protection, and anti-inflammatory and antiplatelet effects, which support the beneficial effects of PDE5 inhibitors in CVD. In experimental models, PDE5 inhibitors reduced myocardial ischemic reperfusion injury and arrhythmia, confirming their cardioprotective effect. Early clinical trials examined the effect of PDE5 inhibitors in patients with concomitant diabetes mellitus and showed a reduction in the incidence of myocardial infarction and mortality. Recent large cohort studies examined the long-term effects of PDE5 inhibitors on the risk of CVD and cardiovascular events. Two studies showed a significant reduction in the risk of MACE with tadalafil therapy by 19% (OR=0,81) and the risk of MACE/venous thromboembolism by 41% (OR=0,59). In a new study, the use of sildenafil and tadalafil led to a 34% and 44% reduction in the risk of mortality (OR=0,76 and OR=0,66), as well as a significant reduction in the risk of myocardial infarction, stroke, venous thromboembolism and even dementia in patients with ED and LUTS, with tadalafil having an advantage over sildenafil. According to the results of a meta-analysis of 16 studies, PDE5 inhibitors reduced the risk of MACE by 22% (OR=0,78) and the risk of overall mortality by 30%
(OR=0,70).
Thus, new data on PDE-5 inhibitors were obtained, confirming not only the safety of the cardiovascular system, but also showing the presence of important cardioprotective properties.

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About the Authors

Marina V. Leonova, Dr. Sci. (Med.), Professor, Corresponding Member of the Russian Academy of Natural Sciences, Member of the Interregional Public Organization of the Association of Clinical Pharmacologists (Moscow Branch), Moscow, Russia; anti23@mail.ru, ORCID:
https://orcid.org/0000-0001-8228-1114, eLibrary SPIN: 3281-7884

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