Cilostazol and Risk of Major Adverse Limb and Cardiovascular Events after Revascularisation for Peripheral Artery Disease

OBJECTIVE: Patients with peripheral artery disease (PAD) remain at high risk of major adverse limb events (MALE) and cardiovascular events (MACE) after revascularisation. Cilostazol, a phosphodiesterase-3 inhibitor with antiplatelet and antiproliferative effects, reduces re-stenosis but its real world impact on clinical outcomes is uncertain. This retrospective, nationwide, propensity score matched cohort study evaluated the effectiveness and safety of cilostazol on MALE, MACE, and all cause mortality after lower limb revascularisation for PAD. METHODS: Using the Taiwan National Health Insurance Research Database, patients who underwent lower limb revascularisation for PAD from 2010 - 2023, with follow up through 2024 were identified. Patients with prior cilostazol use were excluded. 1:1 propensity score matching (n = 5 464 per group) adjusted for baseline differences. Cox regression and Fine-Gray competing risk models were used to evaluate outcomes. The comparison reflects cilostazol used with or without background antithrombotic therapy. RESULTS: Cilostazol use was associated with significantly lower risks of MALE (78.7 vs. 154.0 events/1 000 person-years; subdistribution hazard ratio [SHR] 0.50; 95% confidence interval [CI] 0.46 - 0.53) and MACE (97.9 vs. 117.1 events/1 000 person-years; hazard ratio [HR] 0.84; 95% CI 0.79 - 0.89). All cause mortality was also reduced (116.0 vs. 127.6 events/1 000 person-years; HR 0.91; 95% CI 0.86 - 0.96). Major bleeding did not differ significantly between groups (SHR 0.90; 95% CI 0.81 - 1.00), although the absolute rate was high in both groups (12.1% vs. 13.1%). Subgroup analysis showed greater limb benefit in patients not on other antiplatelet agents. CONCLUSION: Cilostazol after PAD revascularisation was associated with lower risks of limb and cardiovascular events and mortality. These effects were observed without any increase in the rate of major bleeding, although this rate was high in both groups. Randomised trials focused on cardiovascular events are needed.