Effectiveness and Safety of Enteric-Coated vs Uncoated Aspirin in Patients With Cardiovascular Disease: A Secondary Analysis of the ADAPTABLE Randomized Clinical Trial.
Academic Article
Overview
abstract
BACKGROUND: The appropriate dosage of aspirin to lower the risk of death, myocardial infarction (MI), and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease (ASCVD) has not been determined. OBJECTIVES: To determine the optimal dosage of aspirin to be used in people with ASCVD to prevent the occurrence of major adverse cardiovascular events. METHODS: Using an open-label, pragmatic design, we randomly assigned patients with established ASCVD to a strategy of 81 mg or 325 mg of aspirin per day. Using intention-to-treat methods, the primary effectiveness outcome was a composite of death from any cause, hospitalization for MI, or hospitalization for stroke, assessed in a time-to-event analysis. The primary safety outcome was hospitalization for major bleeding, also assessed in a time-to-event analysis. RESULTS: A total of 15 076 patients were followed for a median (IQR) of 26.2 (19.0-34.9) months. Before randomization, 13 537 of those patients (96.0% of those with available information about previous aspirin use) were already taking aspirin, and 85.3% were previously taking 81 mg of aspirin per day. Death, hospitalization for MI, or hospitalization for stroke occurred in 590 patients (estimated percentage, 7.28%) in the 81-mg group and 569 patients (estimated percentage, 7.51%) in the 325-mg group (hazard ratio, 1.02 [95% CI, 0.91-1.14]). Hospitalization for major bleeding occurred in 53 patients (estimated percentage, 0.63%) in the 81-mg group and 44 patients (estimated percentage, 0.60%) in the 325-mg group (hazard ratio, 1.18 [95% CI, 0.79-1.77]). Patients assigned to 325 mg had a higher incidence of dose switching than those assigned to 81 mg (41.6% vs 7.1%) and fewer median (IQR) days of exposure to the assigned dose (434 [139-737] days vs 650 [415-922] days). CONCLUSIONS: In this pragmatic trial involving patients with established CVD, there was substantial dose switching to 81 mg aspirin per day and no significant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg aspirin daily. LIMITATIONS: Several important limitations must be acknowledged, including that the study was conducted in an open-label fashion, a high incidence of dose switching occurred in the 325-mg group, and most participants took 81 mg aspirin daily before the study. Despite attempts to identify and enroll a diverse population of participants with ASCVD, the enrollment of women and patients from traditionally underrepresented groups lagged behind our goals and mirrored enrollment in prior traditional cardiovascular studies. In addition, duration of follow-up was relatively modest for a comparative effectiveness study for cardiovascular outcomes.
