Enteric-Coated vs. Uncoated Aspirin in Patients With CVD
- Enteric-coated aspirin was not found to be associated with any significant differences in effectiveness or safety when compared to uncoated aspirin in patients with established atherosclerotic cardiovascular disease.
- Event rates were similar regardless of aspirin formulation, dose, or presence of an acid-reducing medication.
What is the effectiveness and safety of enteric-coated aspirin compared to uncoated aspirin in patients with cardiovascular disease (CVD)?
This study is a secondary analysis of the ADAPTABLE trial, a multicenter, randomized, controlled trial evaluating two daily doses of aspirin (81 mg vs. 325 mg) in patients with established atherosclerotic CVD (ASCVD). Patients enrolled were aged ≥18 years with known ASCVD and ≥1 enrichment factor (age >65 years, serum creatinine >1.5 mg/dL, type 1 or 2 diabetes, three-vessel coronary artery disease, cerebrovascular disease or peripheral arterial disease, left ventricular ejection fraction <50%, and current cigarette smoker), no history of significant gastrointestinal (GI) bleeding within prior 12 months, and not currently treated with an oral anticoagulant or ticagrelor.
The primary effectiveness endpoint was time to first occurrence of any event in the composite of death from any cause, hospitalization for myocardial infarction (MI), or hospitalization for stroke. Secondary effectiveness endpoints included the individual components of the primary endpoint, all-cause mortality, revascularization, and transient ischemic attack. The primary safety endpoint was hospitalization for major bleeding requiring a blood product or intracranial hemorrhage. Patients were divided into subgroups based on randomized aspirin dose and self-reported aspirin formulation at the time of randomization. Unadjusted and multivariable Cox proportional hazards models were used for cumulative incidence at median follow-up of endpoints between participants taking enteric-coated or uncoated aspirin. An interaction term was included to assess whether the association of aspirin formulation was consistent across randomly assigned aspirin doses.
Of the 15,076 participants from the ADAPTABLE study, 10,678 (70.1%) reported the aspirin formulation used (69% enteric-coated and 31% uncoated). The median age was 68 years (interquartile range, 61.3-73.7 years) and 68.2% of participants were men. The majority of participants were White (84%), followed by Black or African American (8.4%), other race (4.5%), and Hispanic (2.5%). Use of enteric-coated aspirin was reported by 54% of participants in the 81 mg dose group and 44.3% of participants in the 325 mg dose group. At the time of enrollment, 22% of participants in both aspirin groups were taking a P2Y12 inhibitor. Acid-reducing medication (ARMs) were used more commonly by participants taking enteric-coated aspirin compared with uncoated aspirin (38% vs. 35%, p < 0.002).
There was no significant difference in effectiveness (adjusted hazard ratio [AHR], 0.94; 95% confidence interval [CI], 0.80-1.09; p = 0.40) or safety (AHR, 0.82; 95% CI, 0.49-1.37; p = 0.46) outcomes between enteric-coated and uncoated aspirin cohorts. Event rates for all effectiveness outcomes were similar regardless of assigned dose group. Overall major bleeding in ADAPTABLE was low. There was no significant interaction of major bleeding across all four aspirin formulation and dose cohorts. There was a small but significant increase in major bleeding with 325 mg enteric-coated aspirin (AHR, 2.37; 95% CI, 1.02-5.50) but no significant difference in the uncoated aspirin cohort. GI bleeding was also similar across formulation and dose cohorts and there were no significant interactions between enteric coating and the presence of ARM on any endpoint.
There were no significant differences in MI, stroke, or death or risk of major bleeding between enteric-coated and uncoated aspirin, regardless of dose, in this post hoc analysis of patients with established ASCVD enrolled in the ADAPTABLE trial.
Although prior pharmacodynamic studies have shown enteric coating hinders dissolution of aspirin in the small intestine and limits overall drug bioavailability, the present analysis suggests no impact on clinical effectiveness or safety when compared to uncoated aspirin. Additionally, use of ARMs was not shown to alter these findings. Enteric-coated aspirin is often recommended to patients with ASCVD over uncoated formulations to minimize GI tract ulceration and bleeding. The results of this analysis as well as the ADAPTABLE trial should promote further discussion with individual patients regarding the appropriate formulation and dose of aspirin for secondary prevention of ASCVD.
Clinical Topics: Prevention
Keywords: Aspirin, Atherosclerosis, Secondary Prevention
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