Phosphodiesterase-5 inhibitors for cerebral small vessel disease-related ischemic stroke and cognitive decline: systematic review and meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 42051769 · doi:10.3389/fneur.2026.1776589
What was done
Authors conducted a systematic review and random-effects meta-analysis of randomized controlled trials published between January 1990 and October 2025 assessing sildenafil or tadalafil in adults with cerebral small vessel disease (CSVD). Primary outcomes evaluated were cerebral blood flow (CBF) in white matter hyperintensity regions, middle cerebral artery mean flow velocity, standardized cognitive assessments, blood pressure changes, and adverse events.
What was found
Four studies comprising 236 patients were included. PDE5 inhibitors significantly increased CBF in white matter hyperintensity regions versus placebo (MD = 1.31 mL/100 g/min, 95% CI: 0.46 to 2.15, p = 0.002) and reduced diastolic blood pressure (MD = -4.65 mmHg, 95% CI: -5.96 to -3.34, p < 0.00001). The effect on cerebral blood flow velocity was not statistically significant (p > 0.05). No significant cognitive improvements were observed across any domain. Risk of adverse events was significantly increased with PDE5 inhibitors (RR = 2.36, 95% CI: 1.53 to 3.65, p = 0.0001), though no severe adverse events occurred.
Why it matters
Although PDE5 inhibitors improve regional microvascular hemodynamics in CSVD, current clinical trial data do not show translating benefits on cognitive function.
Limits
The total sample size is small (4 trials, 236 participants). Treatment durations, specific cognitive test batteries, and long-term functional or stroke outcomes are not detailed in the abstract.
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