Phosphodiesterase type 5 Inhibitors (PDE-5I) as a potential therapeutic drug in stroke: A systematic narrative review

Abstract

Objectives. Stroke is an acute cerebrovascular disease with high morbidity and mortality rate. Many stroke management strategies can improve prognosis and quality of life, but only to a certain extent. Phosphodiesterase inhibitor-5 (PDE-5i) has shown benefits in numerous preclinical studies, but human studies have been inconclusive. Material and Methods. For this narrative review, we conducted a systematic search following the PRISMA statement guideline from inception until November 2022. The search was conducted in PubMed, ScienceDirect, EBSCOhost, and ProQuest. We included all human and animal studies on this topic, including preclinical studies, randomized clinical trials, and case studies. All the excluded studies are reviews or non-English studies. Review. Many PDE-5i have shown benefits in anatomical and functional outcomes in preclinical acute experimental stroke models. PF-03049423 was safe and well tolerated in humans but had no significant impact on neurological or functional outcomes. Sildenafil on acute/subacute was deemed safe to use and demonstrated improvement over baseline, but power remains unknown due to the lack of a control group. Tadalafil use resulted in a reduction in regional cerebral blood flow in subjects with a history of stroke. Conclusions. Despite promising results in preclinical studies, current evidence shows that PDE-5i does not affect clinical or functional recovery in people with acute stroke. The disparity in the intricacy of stroke pathophysiology between human and animal models was crucial. Further research in a larger population with more consistent stroke onset, medicines, and doses is required for a more conclusive result.