Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease and Diabetes Mellitus: A Subgroup Analysis of the ADAPTABLE Trial

Background: Patients with diabetes mellitus and concomitant atheterosclerotic cardiovascular disease (ASCVD) must be on the most effective dose of aspirin to mitigate risk of future adverse cardiovascular events.

Methods: ADAPTABLE, an open-label, pragmatic study, randomized patients with stable, chronic ASCVD to 81 mg or 325 mg of daily aspirin. The effects of aspirin dosing was assessed on the primary effectiveness outcome, a composite of all-cause death, hospitalization for myocardial infarction, or hospitalization for stroke, and the primary safety outcome of hospitalization for major bleeding. In this pre-specified analysis, we used Cox proportional hazards models to compare aspirin dosing in patients with and without DM for the primary effectiveness and safety outcome.

Results: Of 15,076 patients, 5,676 (39%) had DM of which 2,820 (49.7%) were assigned to 81 mg and 2,856 (50.3%) to 325 mg of aspirin. Patients with vs. without DM had higher rates of the composite cardiovascular outcome (9.6% vs 5.9%, p < 0.001) and bleeding events (0.78% vs 0.50%, p < 0.001). When comparing 81 mg vs. 325 mg of aspirin, patients with DM had no difference in the primary effectiveness outcome (9.3% vs 10.0%; HR 0.98; 95% CI 0.83-1.16, p = 0.265) or safety outcome (0.87% vs 0.69%; subdistribution HR 1.25; 95% CI 0.72 – 2.16, p = 0.772).

Conclusions: This study confirms the inherently higher risk of patients with DM irrespective of aspirin dosing. Our findings suggest higher dose of aspirin yields no added clinical benefit even in a more vulnerable population