Associations between phosphodiesterase type 5 inhibitors and vascular function: a systematic review and meta-analysis on randomized-controlled trials.

BACKGROUND

Phosphodiesterase type-5 inhibitors (PDE5is) are used for the treatment of erectile dysfunction (ED) and have potential cardioprotective effects. The impacts of PDE5is on cardiovascular parameters, which may be associated with the occurrence and progression of subclinical cardiovascular diseases, remain uncertain. In this study, we evaluated the effects of PDE5is on vascular parameters.

METHODS

Randomized controlled trials (RCTs) that compared the effects of PDE5is and placebo on vascular parameters and were published from 1998 to 2022 were identified from PubMed, Scopus and Web of Science. Mean differences (MDs) with 95% confidence intervals (CIs) were pooled. A sensitivity analysis was conducted to confirm the robustness of the pooled results. The keywords that were searched in the databases are as follows: ((systolic blood pressure) OR (SBP) OR (diastolic blood pressure) OR (DBP) OR (mean arterial pressure) OR (MAP) OR (Pulse Wave Velocity) OR (PWV) OR (intima-media thickness) OR (cIMT) OR (augmentation Index) OR (AI) OR (FMD) OR (flow-mediated dilation) OR (reactive hyperemia index) OR (RHI) OR (Endothelial microparticles) OR (EMP) OR (EPCs) OR (Endothelial Progenitor Cells) OR (PSV) OR (peak systolic velocity)) AND ((PDE5 Inhibitors) OR (PDE5i) OR (Sildenafil) OR (Vardenafil) OR (Tadalafil) OR (Lodenafil) OR (Udenafil) OR (Avanafil)).

RESULTS

Sixty-three studies involving 3242 subjects were included. Overall, PDE5is decreased systolic blood pressure (MD: -2.80 mmHg, 95% CI: -4.24, -1.37, P < 0.001), diastolic blood pressure (MD: -1.80 mmHg, 95% CI: -2.37, -1.22, P < 0.001), carotid intima‒media thickness (MD: -0.01 mm, 95% CI: -0.02, -0.01, P < 0.001), and pulse wave velocity (MD: -0.75 cm/s, 95% CI: -1.01, -0.49, P < 0.001). In addition, PDE5is increased the peak systolic velocity (MD: 3.70 cm/s, 95% CI: 3.52, 3.88, P < 0.001), flow-mediated dilation (MD: 2.47%, 95% CI: 1.24, 3.71, P < 0.001), concentration of endothelial progenitor cells (MD: 475.29 cells/mL, 95% CI: 51.38, 899.20, P = 0.03), and concentration of endothelial microparticles (MD: 4.86%, 95% CI: 0.65, 9.07, P = 0.02). However, the effects of PDE5is on the augmentation index, brachial artery diameter and reactive hyperemia index were not statistically significant.

CONCLUSION

Compared with the placebo, PDE5is improved vascular parameters, indicating the potential of PDE5is for treating subclinical cardiovascular diseases. Further research is needed to confirm the role of the improvement on vascular parameters by PDE5isin preventing and treating cardiovascular diseases.

SYSTEMATIC REVIEW REGISTRATION: The present study protocol was reviewed and approved by PROSPERO. The title is "Associations between PDE5is and vascular parameters: A systematic review and meta-analysis" ( https://www.crd.york.ac.uk/PROSPERO/ ) (Reg. No. CRD42023387924).