Phosphodiesterase-5 inhibitors for cerebral small vessel disease-related ischemic stroke and cognitive decline: systematic review and meta-analysis
Abstract
BACKGROUND AND OBJECTIVES: Cerebral small vessel disease (CSVD) represents a major contributor to both cerebral ischemic events and the development of vascular cognitive decline. Based on preclinical evidence, phosphodiesterase-5 inhibitors (PDE5-Is) may benefit neurovascular function, this systematic review and meta-analysis evaluated their effects on cerebral hemodynamics, cognitive function, and safety in patients with cerebral small vessel disease (CSVD).
METHODS: We systematically searched four major databases from January 1990 to October 2025 for randomized controlled trials investigating sildenafil or tadalafil in adults with CSVD. Primary outcomes included changes in cerebral blood flow in white matter hyperintensity regions, mean flow velocity in the middle cerebral artery, and performance on standardized cognitive assessments. Data were synthesized using random-effects models.
RESULTS: Four studies involving 236 patients were included. Meta-analysis showed that PDE5-Is significantly increased cerebral blood flow in white matter hyperintensity regions (MD = 1.31 mL/100 g/min, 95% CI: 0.46-2.15, p = 0.002) compared to placebo, but the overall effect of PDE5-Is inhibitors on cerebral blood flow velocity was not statistically significant (p > 0.05). A modest reduction in diastolic blood pressure was also observed (MD = -4.65 mmHg, 95% CI: -5.96 to -3.34, p < 0.00001). The overall risk of adverse events was increased (RR = 2.36, 95% CI: 1.53-3.65, p = 0.0001), but no…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 236 participants or records.
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