Prognostic Implications of Single Antiplatelet Therapy in Individuals Developing Diabetic Foot Disease with Concurrent Peripheral Arterial Disease
By: Lin CW, Huang YY, Lin CH, et al. | Published in: Annals of Medicine | April 14, 2026
In wound care, we’re trained to reach for the newer, more expensive medication when the evidence looks good and the old one seems tired. A Taiwanese registry study just published in Annals of Medicine challenges that instinct for one of the most common decisions we make in diabetic foot practice: which single antiplatelet to prescribe after a patient has had their first diabetic foot event with peripheral arterial disease.
The researchers at Chang Gung Memorial Hospital pulled 2,597 adults with type 2 diabetes from the Taiwan Health and Welfare Data Center — every patient had experienced a first diabetic foot disease (DFD) event between 2016 and 2019, every one had concurrent PAD, and every one was subsequently placed on a single antiplatelet agent for secondary prevention after stabilization. The three agents in the comparison: aspirin, clopidogrel, and cilostazol. Outcomes tracked over follow-up: major lower-extremity amputation, major adverse limb events (MALE), major adverse cardiovascular events (MACE), and all-cause mortality. The analysis used inverse probability of treatment weighting to balance the groups and Fine-Gray competing risk models for limb endpoints.
The headline finding runs against expectation. Compared with aspirin, cilostazol was associated with a 45% higher risk of major adverse limb events (sHR 1.45, 95% CI 1.15–1.84). Clopidogrel trended in the same direction on MALE but didn’t reach significance. On all-cause mortality, both alternatives came out worse than aspirin: clopidogrel HR 1.25 (1.07–1.46), cilostazol HR 1.21 (1.06–1.39). Risks of major amputation and MACE didn’t differ significantly across the three agents.
In other words: aspirin matched its pricier rivals on the limb and cardiovascular outcomes we most worry about, and came out ahead on staying alive.
A few caveats worth keeping in mind. This is observational registry data, not a randomized trial — the clopidogrel and cilostazol groups carried higher comorbidity burdens at baseline, and while IPTW is a reasonable tool to adjust for that, residual confounding is always possible. The cohort is entirely Taiwanese; practice patterns and genetics (including CYP2C19 variants that affect clopidogrel response) vary across populations. And the study looked only at patients on monotherapy after stabilization, so nothing here speaks to the question of dual antiplatelet therapy in the acute post-revascularization window.
But for the everyday question — what do I put this patient on for long-term secondary prevention after their first diabetic foot event? — the signal is clear enough to take seriously. The oldest, cheapest, most boring option in the cabinet may still be the right one.
PVM
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