Faculty Collaboration Database

Effectiveness and Safety of Enteric-Coated vs Uncoated Aspirin in Patients With Cardiovascular Disease: A Secondary Analysis of the ADAPTABLE Randomized Clinical Trial. JAMA Cardiol 2023 Nov 01;8(11):1061-1069

Date

10/04/2023

Pubmed ID

37792369

Pubmed Central ID

PMC10551818

DOI

10.1001/jamacardio.2023.3364

Scopus ID

2-s2.0-85176508832 (requires institutional sign-in at Scopus site)   2 Citations

Abstract

IMPORTANCE: Clinicians recommend enteric-coated aspirin to decrease gastrointestinal bleeding in secondary prevention of coronary artery disease even though studies suggest platelet inhibition is decreased with enteric-coated vs uncoated aspirin formulations.

OBJECTIVE: To assess whether receipt of enteric-coated vs uncoated aspirin is associated with effectiveness or safety outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This is a post hoc secondary analysis of ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness), a pragmatic study of 15 076 patients with atherosclerotic cardiovascular disease having data in the National Patient-Centered Clinical Research Network. Patients were enrolled from April 19, 2016, through June 30, 2020, and randomly assigned to receive high (325 mg) vs low (81 mg) doses of daily aspirin. The present analysis assessed the effectiveness and safety of enteric-coated vs uncoated aspirin among those participants who reported aspirin formulation at baseline. Data were analyzed from November 11, 2019, to July 3, 2023.

INTERVENTION: ADAPTABLE participants were regrouped according to aspirin formulation self-reported at baseline, with a median (IQR) follow-up of 26.2 (19.8-35.4) months.

MAIN OUTCOMES AND MEASURES: The primary effectiveness end point was the cumulative incidence of the composite of myocardial infarction, stroke, or death from any cause, and the primary safety end point was major bleeding events (hospitalization for a bleeding event with use of a blood product or intracranial hemorrhage). Cumulative incidence at median follow-up for primary effectiveness and primary safety end points was compared between participants taking enteric-coated or uncoated aspirin using unadjusted and multivariable Cox proportional hazards models. All analyses were conducted for the intention-to-treat population.

RESULTS: Baseline aspirin formulation used in ADAPTABLE was self-reported for 10 678 participants (median [IQR] age, 68.0 [61.3-73.7] years; 7285 men [68.2%]), of whom 7366 (69.0%) took enteric-coated aspirin and 3312 (31.0%) took uncoated aspirin. No significant difference in effectiveness (adjusted hazard ratio [AHR], 0.94; 95% CI, 0.80-1.09; P = .40) or safety (AHR, 0.82; 95% CI, 0.49-1.37; P = .46) outcomes between the enteric-coated aspirin and uncoated aspirin cohorts was found. Within enteric-coated aspirin and uncoated aspirin, aspirin dose had no association with effectiveness (enteric-coated aspirin AHR, 1.13; 95% CI, 0.88-1.45 and uncoated aspirin AHR, 0.99; 95% CI, 0.83-1.18; interaction P = .41) or safety (enteric-coated aspirin AHR, 2.37; 95% CI, 1.02-5.50 and uncoated aspirin AHR, 0.89; 95% CI, 0.49-1.64; interaction P = .07).

CONCLUSIONS AND RELEVANCE: In this post hoc secondary analysis of the ADAPTABLE randomized clinical trial, enteric-coated aspirin was not associated with significantly higher risk of myocardial infarction, stroke, or death or with lower bleeding risk compared with uncoated aspirin, regardless of dose, although a reduction in bleeding with enteric-coated aspirin cannot be excluded. More research is needed to confirm whether enteric-coated aspirin formulations or newer formulations will improve outcomes in this population.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02697916.

Author List

Sleem A, Effron MB, Stebbins A, Wruck LM, Marquis-Gravel G, Muñoz D, Re RN, Gupta K, Pepine CJ, Jain SK, Girotra S, Whittle J, Benziger CP, Farrehi PM, Knowlton KU, Polonsky TS, Roe MT, Rothman RL, Harrington RA, Jones WS, Hernandez AF

Author

Jeffrey Whittle MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged
Aspirin
Cardiovascular Diseases
Double-Blind Method
Gastrointestinal Hemorrhage
Humans
Male
Myocardial Infarction
Platelet Aggregation Inhibitors
Stroke