Comparative effectiveness of dual antiplatelet therapy after revascularization in diabetes and chronic limb-threatening ischemia: a target trial emulation study.
TL;DR
It is suggested that aspirin plus cilostazol may be a favorable DAPT strategy for long-term outcomes in this population of patients with diabetes and CLTI undergoing lower-extremity revascularization, and further prospective randomized trials are warranted to verify.
Abstract
Background
Patients with diabetes and chronic limb-threatening ischemia (CLTI) face high risks of adverse limb and cardiovascular events. While post-revascularization dual antiplatelet therapy (DAPT) is generally recommended, the optimal regimen remains uncertain. This study aimed to compare the effectiveness of different DAPT strategies with respect to long-term clinical outcomes.
Methods
We conducted a nationwide 90-day landmark observational analysis informed by a target trial framework based on healthcare claims data from Taiwan. The cohort included adults with type 2 diabetes who underwent lower-extremity revascularization for new-onset CLTI between 2016 and 2019. Patients were classified according to the post-procedural DAPT strategy initiated within a 90-day grace period. Inverse probability of treatment weighting (IPTW) was used to balance baseline covariates. The outcomes assessed were lower-extremity amputation (LEA), major adverse limb events (MALE), major adverse cardiovascular events (MACE), and all-cause mortality.
Results
The final cohort comprised 1,849 patients (aspirin plus clopidogrel, n = 439; aspirin plus cilostazol, n = 753; clopidogrel plus cilostazol, n = 657). Median follow-up years (IQR) were 2.94 (1.97-4.11) for all-cause mortality, 2.79 (1.62-3.96) for LEA, 2.40 (0.98-3.62) for MALE, and 2.55 (1.24-3.70) for MACE. Following IPTW, baseline characteristics were well balanced. Compared with standard DAPT (aspirin plus clopidogrel), aspirin plus cilostazol was associated with a lower risk of LEA (sHR, 0.672; 95% CI, 0.460-0.981) and MACE (sHR, 0.799; 95% CI, 0.641-0.995). Clopidogrel plus cilostazol did not demonstrate significant limb-related advantages but was associated with a lower incidence of MACE (sHR, 0.790; 95% CI, 0.631-0.989). All-cause mortality was comparable across all three regimens. Notably, in stratified analyses, the clinical benefits of cilostazol-based therapies were attenuated and statistically non-significant among patients receiving dialysis.
Conclusions
Among patients with diabetes and CLTI undergoing lower-extremity revascularization, aspirin plus cilostazol was associated with lower risks of LEA and MACE compared with aspirin plus clopidogrel, whereas clopidogrel plus cilostazol was associated with lower MACE but not with significant limb-related benefit. These observational findings suggest that aspirin plus cilostazol may be a favorable DAPT strategy for long-term outcomes in this population; however, further prospective randomized trials are warranted to verify.