ABSTRACT NUMBER: ESOC2026A2079 CEREBRAL SMALL VESSEL DISEASE AND PDE INHIBITION: A META-ANALYSIS OF CLINICAL AND COGNITIVE EFFECTS

Abstract Background and aims Cerebral small vessel disease (cSVD) is common and is a major contributor to lacunar stroke, intracerebral hemorrhage, and vascular cognitive impairment. Disease-modifying therapies remain limited, motivating interest in vasodilatory and neurovascular-targeted approaches, including phosphodiesterase (PDE) inhibitors. Our aim is to evaluate randomized trial evidence on PDE inhibitor therapy in adults with cSVD and to measure the effects on cognitive function score and recurrent stroke and major vascular events. Methods We performed a systematic review and meta-analysis in adult patients with cSVD receiving vasodilator drugs, focusing here on PDE inhibitors. We search Medline/PubMed, Scopus, Embase and Cochrane CENTRAL from inception till Jan 2026. For meta-analyses we used inverse-variance methods; standardized mean difference (Cohen’s d) for cognitive function score and log risk ratio for recurrent stroke/major vascular events; heterogeneity summarized with I2. Results For cognitive function score, the pooled standardized mean difference was −0.10 (95% CI −0.76 to 0.56), with substantial heterogeneity (I2=85.56%). While recurrent stroke and major vascular events the pooled effect was log RR = −1.16 (95% CI −2.06 to −0.26; p=0.01) this corresponds to RR = 0.31 (95% CI 0.13 to 0.77) . Conclusions Across available trials in cSVD, PDE inhibitor therapy showed no clear pooled effect on cognitive function score with high between-study heterogeneity but suggested a lower risk of recurrent stroke/major vascular events in the pooled log RR analysis. The evidence base remains limited by small event counts, and non-identical event definitions. Conflict of interest All Authors have nothing to disclose Figure 1 - belongs to Results