Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness - ADAPTABLE

Aug 09, 2024
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Author/Summarized by Author:
Anthony A. Bavry, MD,MPH,FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC; Kim A. Eagle, MD, MACC
Trial Sponsor:
Patient-Centered Outcomes Research Institute
Date Presented:
05/15/2021
Date Published:
07/24/2024
Date Updated:
08/09/2024
Original Posted Date:
05/15/2021
References

Contribution To Literature:

Highlighted text has been updated as of August 9, 2024.

The ADAPTABLE trial failed to show that aspirin 325 mg was superior to 81 mg in ASCVD patients.

Description:

The goal of the trial was to evaluate aspirin 81 mg compared with 325 mg among patients with established atherosclerotic cardiovascular disease (ASCVD).

Study Design

  • Randomized
  • Parallel
  • Open-label

Patients with ASCVD were randomized to aspirin 81 mg (n = 7,540) versus aspirin 325 mg (n = 7,536).

  • Total number of enrollees: 15,076
  • Duration of follow-up: 26.2 months
  • Mean patient age: 68 years
  • Percentage female: 31%
  • Percentage with diabetes: 38%

Inclusion criteria:

  • Patients with CVD, defined as: 1) prior myocardial infarction (MI), 2) prior coronary revascularization, 3) prior coronary angiogram with ≥75% coronary stenosis, or 4) history of chronic ischemic heart disease, coronary artery disease (CAD), or ASCVD.
  • At least one additional enrichment factor:
  • Age ≥65 years
  • Creatinine ≥1.5 mg/dl
  • Diabetes mellitus
  • Known three-vessel CAD
  • Cerebrovascular disease
  • Peripheral artery disease
  • Current smoker
  • Known left ventricular ejection fraction <50%
  • Chronic systolic or diastolic heart failure
  • Systolic blood pressure ≥140 mm Hg within the last year
  • Low-density lipoprotein cholesterol ≥130 mg/dl within the last year

Exclusion criteria:

  • Significant allergy to aspirin
  • Gastrointestinal bleeding within the last 12 months
  • Bleeding disorder that precluded aspirin
  • Current or planned use of an oral anticoagulant or ticagrelor
  • Female patients who are pregnant or nursing

Other salient features/characteristics:

  • Aspirin use before the study: 81 mg in 85%, 162 mg in 2.5%, and 325 mg in 12.3%

Principal Findings:

  • The primary effectiveness outcome of all-cause death, MI, or stroke at 12 months occurred in 7.3% of the aspirin 81 mg group compared with 7.5% of the aspirin 325 mg group (p = 0.75).
  • The primary safety outcome of major bleeding requiring blood transfusion at 12 months occurred in 0.6% of the aspirin 81 mg group compared with 0.6% of the aspirin 325 mg group (p = 0.41).
  • The secondary outcome of dose switching occurred in 7.1% in the aspirin 81 mg group compared with 41.6% of the aspirin 325 mg group.

Outcomes according to sex:

  • No treatment interaction by sex for the primary effectiveness endpoint between the two aspirin doses (female adjusted hazard ratio [aHR] 1.01, 95% confidence interval [CI] 0.82-1.26 and male aHR 1.06, 95% CI 0.91-1.23; p for interaction = 0.74)

Contribution of clinical trial event data by data source:

Most events (92%-100%) were identified in the electronic health record (EHR) or in claims data. Participant-reported data contributed <10% of events not otherwise available from claims or EHR data.

Interpretation:

Among patients with ASCVD, aspirin 325 mg was not superior compared with 81 mg. The lack of treatment difference was similar among women and men. Aspirin 325 mg was not associated with a reduction in all-cause death, MI, or stroke compared with 81 mg daily. Major bleeding requiring transfusion was similar between treatment groups. Patients assigned to aspirin 325 mg were more likely to switch to a lower dose than vice versa. In 2014, results from the National Cardiovascular Data Registry revealed that 60% of patients with acute MI were discharged on a dose of 325 mg. However, prior to randomization in ADAPTABLE, 85% of patients were treated with 81 mg, reflecting a change in practice pattern. For most patients with established ASCVD, aspirin 81 mg likely remains preferential due to enhanced adherence.

References:

Rymer JA, Mulder H, Wruck LM, et al. Contribution of Clinical Trial Event Data by Data Source: A Prespecified Analysis of the ADAPTABLE Randomized Clinical Trial. JAMA Cardiol 2024;Jul 24:[Epublished].

Benziger CP, Stebbins A, Wruck LW, et al. Aspirin Dosing for Secondary Prevention of Atherosclerotic Cardiovascular Disease in Male and Female Patients: A Secondary Analysis of the ADAPTABLE Randomized Clinical Trial. JAMA Cardiol 2024;Jul 10:[Epublished].

Jones WS, Mulder H, Wruck LM, et al., on behalf of the ADAPTABLE Team. Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease. N Engl J Med 2021;384:1981-90.

Editorial: Baigent C. Pragmatic Trials — Need for ADAPTABLE Design. N Engl J Med 2021;384:2065-6.

Presented by Dr. William Schuyler Jones at the American College of Cardiology Virtual Annual Scientific Session (ACC 2021), May 15, 2021.

Clinical Topics: Anticoagulation Management, Prevention

Keywords: ACC21, ACC Annual Scientific Session, Anticoagulants, Aspirin, Atherosclerosis


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