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Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease
W Schuyler Jones1, Hillary Mulder1, Lisa M Wruck1
1From Duke Clinical Research Institute, Duke University, Durham (W.S.J., H.M., L.M.W., M.J.P., M.T.R., H.R.R., L.H.C., A.G.S., L.G.B., B.G.H., D.F.H., L.G.Q., G.M.-G., A.F.H.), University of North Carolina at Chapel Hill, Chapel Hill (D.A.D.), and Wake Forest University School of Medicine, Winston-Salem (L.Z.) - all in North Carolina; Vanderbilt University Medical Center, Nashville (S.K., D.M., D.L.C., R.L.R.); Ochsner Health (M.B.E., R.N.R.) and Louisiana Public Health Institute (T.W.C., E.N.) - both in New Orleans; University of Kansas Medical Center, Kansas City (K.G.); University of Florida, Gainesville (R.D.A., C.J.P., E.M.H., B.R.M., E.A.S.); University of Pittsburgh Medical Center, Pittsburgh (S.K.J., K.M.M.), Penn State College of Medicine, Hershey (J.L.K.), and Temple University, Philadelphia (A.P.) - all in Pennsylvania; University of Iowa, Iowa City (S.G., D.R.); Medical College of Wisconsin, Milwaukee (J.W.), and Marshfield Clinic Research Institute, Marshfield (J.J.V.) - both in Wisconsin; Albert Einstein College of Medicine, Bronx (Y.H.G.), and Weill Cornell Medicine and New York-Presbyterian Hospital, New York (R.K.) - both in New York; Mayo Clinic, Rochester (V.L.R.), Essentia Health Heart and Vascular Center, Duluth (C.P.B.), and Allina Health and Minneapolis Heart Institute, Minneapolis (S.M.B.) - all in Minnesota; University of Utah School of Medicine (R.H.) and Intermountain Medical Center Heart Institute (K.U.K.) - both in Salt Lake City; University of Michigan, Ann Arbor (P.F.); Johns Hopkins University School of Medicine, Baltimore (D.E.F.); HealthCore, Wilmington, DE (K.H.); University of Chicago Medicine (T.S.P.) and Northwestern University Feinberg School of Medicine (D.J.F., F.S.A., A.M.K.) - both in Chicago; University of Nebraska Medical Center, Omaha (J.C.M., J.R.C.); University of California, Los Angeles, Los Angeles (D.S.B., G.C.F.), University of California, San Francisco, San Francisco (M.F.M., G.M.M.), and Stanford University School of Medicine, Stanford (R.A.H.) - all in California; University of Missouri School of Medicine, Columbia (L.R.W.); University of Colorado School of Medicine, Anschutz Medical Campus, Aurora (F.A.M.); Brigham and Women's Hospital, Harvard Medical School, Boston (E.M.A.); Chicago (D.R.D.); St. Joseph, MO (K.E.); Brighton, MI (J.G.M.); Columbia, TN (L.S.B.); Alachua, FL (D.N.Z.); Columbia, MD (T.E.M.); North Hills, CA (J.D.A.); and Metairie, LA (K.C.G.).
Insights
In patients with established cardiovascular disease, daily aspirin doses of 81 mg and 325 mg showed no significant differences in cardiovascular events or major bleeding. Most patients switched to the lower 81 mg dose, indicating a preference for this aspirin regimen.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Aspirin dosing for secondary prevention in atherosclerotic cardiovascular disease (ASCVD) remains controversial.
- Optimal aspirin dosage aims to balance reducing cardiovascular events against minimizing bleeding risk.
Purpose of the Study:
- To compare the effectiveness and safety of two daily aspirin doses (81 mg vs. 325 mg) in patients with established ASCVD.
- To assess cardiovascular outcomes and major bleeding events in patients randomized to different aspirin strategies.
Main Methods:
- An open-label, pragmatic randomized trial (ADAPTABLE) assigned 15,076 patients with established ASCVD to 81 mg or 325 mg of daily aspirin.
- Primary effectiveness outcome: composite of all-cause death, myocardial infarction, or stroke.
- Primary safety outcome: hospitalization for major bleeding.
Main Results:
- No significant differences were observed in the primary effectiveness outcome (7.28% in 81-mg group vs. 7.51% in 325-mg group).
- No significant differences were observed in the primary safety outcome of major bleeding (0.63% in 81-mg group vs. 0.60% in 325-mg group).
- Substantial dose switching occurred, with 41.6% of patients in the 325-mg group switching to 81 mg, compared to 7.1% in the 81-mg group.
Conclusions:
- In patients with established cardiovascular disease, there were no significant differences in cardiovascular events or major bleeding between 81 mg and 325 mg of daily aspirin.
- Pragmatic trial design revealed substantial patient preference for switching to the lower 81 mg aspirin dose.
- Findings suggest that 81 mg daily aspirin is a reasonable strategy for patients with established ASCVD.
Background:
The appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy.
Methods:
Using an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, 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 of 26.2 months (interquartile range [IQR], 19.0 to 34.9). Before randomization, 13,537 (96.0% of those with available information on previous aspirin use) were already taking aspirin, and 85.3% of these patients were previously taking 81 mg of daily aspirin. Death, hospitalization for myocardial infarction, 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% confidence interval [CI], 0.91 to 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 to 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 days of exposure to the assigned dose (434 days [IQR, 139 to 737] vs. 650 days [IQR, 415 to 922]).
Conclusions:
In this pragmatic trial involving patients with established cardiovascular disease, there was substantial dose switching to 81 mg of daily aspirin and no significant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily. (Funded by the Patient-Centered Outcomes Research Institute; ADAPTABLE ClinicalTrials.gov number, NCT02697916.).
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