Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease.

Abstract

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.).

• Authors: W Schuyler Jones, Hillary Mulder, Lisa M Wruck, Michael J Pencina, Sunil Kripalani, Daniel Muñoz, David L Crenshaw, Mark B Effron, Richard N Re, Kamal Gupta, R David Anderson, Carl J Pepine, Eileen M Handberg, Brittney R Manning, Sandeep K Jain, Saket Girotra, Danielle Riley, Darren A DeWalt, Jeff Whittle, Ythan H Goldberg, Veronique L Roger, Rachel Hess, Catherine P Benziger, Peter Farrehi, Li Zhou, Daniel E Ford, Kevin Haynes, Jeffrey J VanWormer, Kirk U Knowlton, Jennifer L Kraschnewski, Tamar S Polonsky, Dan J Fintel, Faraz S Ahmad, James C McClay, James R Campbell, Douglas S Bell, Gregg C Fonarow, Steven M Bradley, Anuradha Paranjape, Matthew T Roe, Holly R Robertson, Lesley H Curtis, Amber G Sharlow, Lisa G Berdan, Bradley G Hammill, Debra F Harris, Laura G Qualls, Guillaume Marquis-Gravel, Madelaine F Modrow, Gregory M Marcus, Thomas W Carton, Elizabeth Nauman, Lemuel R Waitman, Abel N Kho, Elizabeth A Shenkman, Kathleen M McTigue, Rainu Kaushal, Frederick A Masoudi, Elliott M Antman, Desiree R Davidson, Kevin Edgley, James G Merritt, Linda S Brown, Doris N Zemon, Thomas E McCormick 3rd, Jacqueline D Alikhaani, Kenneth C Gregoire, Russell L Rothman, Robert A Harrington, Adrian F Hernandez, ADAPTABLE Team
• Journal: The New England journal of medicine (N Engl J Med) Vol. 384 Issue 21 Pg. 1981-1990 (05 27 2021) ISSN: 1533-4406 [Electronic] United States
• PMID: 33999548 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Pragmatic Clinical Trial, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Massachusetts Medical Society.

Chemical References

• Platelet Aggregation Inhibitors
• Aspirin

Topics

• Aged
• Aspirin (administration & dosage, adverse effects)
• Atherosclerosis (drug therapy)
• Cardiovascular Diseases (drug therapy, mortality, prevention & control)
• Female
• Hemorrhage (chemically induced)
• Hospitalization
• Humans
• Male
• Medication Adherence (statistics & numerical data)
• Middle Aged
• Myocardial Infarction (epidemiology, prevention & control)
• Platelet Aggregation Inhibitors (administration & dosage, adverse effects)
• Secondary Prevention
• Stroke (epidemiology, prevention & control)