Abstract 4361577: Cilostazol and Pentoxifylline Effect on Cognitive Dysfunctions in Patients with Atherosclerotic Cardiovascular Diseases - A Systemic Review of Clinical Evidence

Introduction: The prevalence of executive dysfunctions and attention deficits is increasingly recognized among patients with atherosclerotic cardiovascular disease (ASCVD). Cilostazol (CLZ) and pentoxifylline (PTX) are two potential therapeutic agents that may help reduce the risk of cognitive decline in these patients, likely due to their anti-inflammatory, vasodilatory and endothelial protective effects. However, their comparative efficacy remains unknown. Research Question: CLZ or PTX, which drug is effective in reducing cognitive dysfunctions in ASCVD patients? Methods: A systematic review (SR) was conducted following a comprehensive literature search including RCTs, narrative review, retrospective, and prospective studies. The individual effects of both therapies were evaluated with respect to their potential to reduce vascular stress and improve cognitive dysfunction. Results: This SR compares CLZ versus PTX in 19,966 subjects across 6 studies carried out in 4 countries including Brazil, Japan, Taiwan, and the United States. PTX significantly reduced C-reactive protein (CRP) (P=0.04), Tumor Necrosis Factor-alpha (TNF-α) (P<0.01) levels, and attenuated the decline in Interleukin-10 (IL-10) compared to placebo (P<0.01), thereby suggesting a potential anti-inflammatory effect (Fernandes et al). Additionally, it enhances blood flow by promoting fibrinolysis, improving erythrocyte flexibility, and reducing neutrophil activation (McCarty et al). On the contrary, CLZ was associated with a 25% reduction in dementia risk (HR 0.75; 95%CI, 0.61–0.92) (Tai et al), and significantly reduced the risk of ischemic (OR 0.68; 95%CI, 0.57–0.81; P<0.0001) and hemorrhagic (OR 0.43; 95%CI, 0.29–0.64; P=0.0001) stroke with a lower risk of bleeding (McHutchison et al). However, RCTs showed no significant improvement in Mini-Mental State Examination (MMSE) scores with cilostazol over 96 weeks (Saito et al). Additionally, post-stroke cognition did not improve significantly, with elevated M1 macrophages potentially contributing to neurological decline (Huang et al). While both drugs show promising effects, CLZ has more supportive cognitive data. Conclusion: Based on current evidence, CLZ and PTX show potential in mitigating cognitive dysfunctions in ASCVD. CLZ has more data linking to reduced dementia and stroke risk, while PTX shows strong anti-inflammatory benefits. If confirmed by future trials, both therapies could be integrated into guidelines as adjuncts for selected patients.