Prognostic implications of single antiplatelet therapy in individuals developing diabetic foot disease with concurrent peripheral arterial disease

BACKGROUND: Antiplatelet therapy is recommended for secondary prevention in patients with diabetes and peripheral arterial disease (PAD), particularly after a diabetic foot event. Nevertheless, the relative effectiveness of aspirin, clopidogrel, and cilostazol for long-term outcomes remains uncertain. METHODS: Using the Taiwan Health and Welfare Data Center database, we identified 2,597 adults with type 2 diabetes who experienced their first diabetic foot disease (DFD) event with concurrent PAD between 2016 and 2019 and subsequently received a single antiplatelet agent for secondary prevention after stabilization. Outcomes included major lower extremity amputation (LEA), major adverse limb events (MALE), major adverse cardiovascular events (MACE), and all-cause mortality. Inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazards and Fine-Gray competing risk models were used to estimate hazard ratios (HRs) and subdistribution HRs (sHRs) with 95% confidence intervals (CIs). RESULTS: Baseline characteristics indicated higher comorbidity burdens in the clopidogrel and cilostazol groups. After adjustment, the risks of LEA and MACE did not differ significantly among treatment groups. Compared with aspirin, cilostazol was associated with a higher risk of MALE (sHR 1.45 [95% CI 1.15-1.84]), whereas clopidogrel showed a nonsignificant trend (sHR 1.31 [95% CI 0.99-1.72]). Both cilostazol (HR 1.21 [95% CI 1.06-1.39]) and clopidogrel (HR 1.25 [95% CI 1.07-1.46]) were associated with higher all-cause mortality. Exploratory subgroup analyses showed no significant mortality differences among dialysis patients, and sensitivity analyses yielded consistent results. CONCLUSIONS: Among diabetic patients with PAD and a history of a foot event, aspirin was associated with comparable limb and cardiovascular outcomes, and potentially favorable survival, compared with clopidogrel or cilostazol. These observational findings suggest aspirin is a practical antiplatelet option for secondary prevention in this high-risk population, though further precise trials are needed to verify.