Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease
Open accessAbstract
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.).
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the ADAPTABLE trial of individuals with established CVD (38% with diabetes), there were no significant differences in cardiovascular events or major bleeding between individuals assigned to 81 mg and those assigned to 325 mg aspirin daily.
“In the ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness) trial of individuals with established CVD, 38% of whom had diabetes, there were no significant differences in cardiovascular events or major bleeding between individuals assigned to 81 mg and those assigned to 325 mg aspirin daily (185).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [185]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredIn the ADAPTABLE trial, there were no significant differences in cardiovascular events or major bleeding between individuals assigned to 81 mg and those assigned to 325 mg of aspirin daily.
“In the ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness) trial of individuals with established cardiovascular disease, 38% of whom had diabetes, there were no significant differences in cardiovascular events or major bleeding between individuals assigned to 81 mg and those assigned to 325 mg of aspirin daily (191).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [191]
In ADAPTABLE, cardiovascular events and major bleeding did not differ significantly between aspirin 81 mg and 325 mg daily.
“In the ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefi ts and Long-term Effectiveness) trial of individuals with established cardiovascular disease, 38% of whom had diabetes, there were no signi fi cant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily (156).”
From 10. Cardiovascular Disease and Risk Management: <i>Standards of Care in Diabetes—2023</i> (2023) · cites this paper as [156]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Heart Disease and Stroke Statistics—2020 Update: A Report From the American Heart Association
Virani, S. S., Alonso, A., Benjamin, E. J., Bittencourt, M. S., Callaway, C. W., Carson, A. P., Chamberlain, A. M., Chang, A. R., Cheng, S., Delling, F. N., et al. (2020) · Circulation · doi:10.1161/cir.0000000000000757 · Cited by 9,175 · see citing works
The PRECIS-2 tool: designing trials that are fit for purpose
Loudon, K., Treweek, S., Sullivan, F., Donnan, P., Thorpe, K. E., & Zwarenstein, M. (2015) · BMJ · doi:10.1136/bmj.h2147 · Cited by 1,846 · see citing works
Ford, I., & Norrie, J. (2016) · New England Journal of Medicine · doi:10.1056/nejmra1510059 · Cited by 1,405 · see citing works
Effects of aspirin for primary prevention in persons with diabetes mellitus
The ASCEND Study Collaborative Group (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1804988 · Cited by 1,189 · see citing works
Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly
McNeil, J. J., Wolfe, R., Woods, R. L., Tonkin, A. M., Donnan, G. A., Nelson, M. R., Reid, C. M., Lockery, J. E., Kirpach, B., Storey, E., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1805819 · Cited by 1,139 · see citing works
Gaziano, J. M., Brotons, C., Coppolecchia, R., Cricelli, C., Darius, H., Gorelick, P. B., Howard, G., Pearson, T. A., Rothwell, P. M., Ruilope, L. M., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(18)31924-x · Cited by 883 · see citing works
Dose Comparisons of Clopidogrel and Aspirin in Acute Coronary Syndromes
The CURRENT–OASIS 7 Investigators (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0909475 · Cited by 767 · see citing works
The ADAPTABLE Trial and PCORnet: Shining Light on a New Research Paradigm
Hernandez, A. F., Fleurence, R., & Rothman, R. L. (2015) · Annals of Internal Medicine · doi:10.7326/m15-1460 · Cited by 108 · see citing works
Self-citationMarquis‐Gravel, G., Roe, M. T., Robertson, H. R., Harrington, R. A., Pencina, M. J., Berdan, L. G., Hammill, B. G., Modrow, M. F., Muñoz, D., Fonarow, G. C., et al. (2020) · JAMA Cardiology · doi:10.1001/jamacardio.2020.0116 · Cited by 84 · see citing works
Self-citationRevisiting the Role of Aspirin for the Primary Prevention of Cardiovascular Disease
Marquis‐Gravel, G., Roe, M. T., Harrington, R. A., Muñoz, D., Hernandez, A. F., & Jones, W. S. (2019) · Circulation · doi:10.1161/circulationaha.119.040205 · Cited by 47 · see citing works
Self-citationMahaffey, K. W., Huang, Z., Wallentin, L. C., Storey, R. F., Jennings, L. K., Tricoci, P., White, H. D., Armstrong, P. W., Aylward, P. E., Moliterno, D. J., et al. (2013) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2013.11.052 · Cited by 19 · see citing works
Self-citationFishman, E., Barron, J., Dinh, J., Jones, W. S., Marshall, A., Merkh, R., Robertson, H., & Haynes, K. (2018) · Contemporary Clinical Trials Communications · doi:10.1016/j.conctc.2018.11.001 · Cited by 19 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 8
- [6]Xian Y, Wang TY, McCoy LA, Association of discharge aspirin dose with outcomes after acute myocardial infarction: insights from the Treatment with ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) Study. Circulation 2015; 132: 174– 81. 25995313
- [8]Kohli P, Udell JA, Murphy SA, Discharge aspirin dose and clinical outcomes in patients with acute coronary syndromes treated with prasugrel versus clopidogrel: an analysis from the TRITON-TIMI 38 study (trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-thrombolysis in myocardial infarction 38). J Am Coll Cardiol 2014; 63: 225– 32. 24140678
- [10]Amsterdam EA, Wenger NK, Brindis RG, 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014; 130: 2354– 94. 25249586
- [11]Smith SC Jr, Benjamin EJ, Bonow RO, AHA/ACCF secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation. Circulation 2011; 124: 2458– 73. 22052934
- [12]Montalescot G, Sechtem U, Achenbach S, 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the Management of Stable Coronary Artery Disease of the European Society of Cardiology. Eur Heart J 2013; 34: 2949– 3003. 23996286
- [13]Hall HM, de Lemos JA, Enriquez JR, Contemporary patterns of discharge aspirin dosing after acute myocardial infarction in the United States: results from the National Cardiovascular Data Registry (NCDR). Circ Cardiovasc Qual Outcomes 2014; 7: 701– 7. 25116897
- [18]Ahmad FS, Ricket IM, Hammill BG, Computable phenotype implementation for a national, multicenter pragmatic clinical trial: lessons learned from ADAPTABLE. Circ Cardiovasc Qual Outcomes 2020; 13(6): e006292. 32466729 PMC7321832
- [20]Levine GN, Bates ER, Bittl JA, 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2016; 68: 1082– 115. 27036918
Cited by
Sorted by citations
Isselbacher, E. M., Preventza, O., Hamilton Black, J., Augoustides, J. G., Beck, A. W., Bolen, M. A., Braverman, A. C., Bray, B. E., Brown-Zimmerman, M. M., Chen, E. P., et al. (2022) · Circulation · doi:10.1161/cir.0000000000001106 · Cited by 2,082 · see citing works
2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes.
Marx, N., Federici, M., Schütt, K., Müller-Wieland, D., Ajjan, R. A., Antunes, M. J., Christodorescu, R. M., Crawford, C., Di Angelantonio, E., Eliasson, B., et al. (2023) · European Heart Journal · doi:10.1093/eurheartj/ehad192 · Cited by 1,642 · see citing works
Virani, S. S., Newby, L. K., Arnold, S. V., Bittner, V., Brewer, L. C., Demeter, S. H., Dixon, D. L., Fearon, W. F., Hess, B., Johnson, H. M., et al. (2023) · Circulation · doi:10.1161/cir.0000000000001168 · Cited by 1,598 · see citing works
Rao, S. V., O’Donoghue, M. L., Ruel, M., Rab, T., Tamis-Holland, J. E., Alexander, J. H., Baber, U., Baker, H., Cohen, M. G., Cruz-Ruiz, M., et al. (2025) · Circulation · doi:10.1161/cir.0000000000001309 · Cited by 625 · see citing works
Virani, S. S., Newby, L. K., Arnold, S. V., Bittner, V., Brewer, L. C., Demeter, S. H., Dixon, D. L., Fearon, W. F., Hess, B., Johnson, H. M., et al. (2023) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2023.04.003 · Cited by 596 · see citing works
10. Cardiovascular Disease and Risk Management: <i>Standards of Care in Diabetes—2023</i>
ElSayed, N. A., Aleppo, G., Aroda, V. R., Bannuru, R. R., Brown, F. M., Bruemmer, D., Collins, B. S., Das, S. R., Hilliard, M. E., Isaacs, D., et al. (2023) · Diabetes Care · doi:10.2337/dc23-s010 · Cited by 465 · see citing works
10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025
American Diabetes Association Professional Practice Committee, ElSayed, N. A., McCoy, R. G., Aleppo, G., Balapattabi, K., Beverly, E. A., Briggs Early, K., Bruemmer, D., Das, S. R., Echouffo-Tcheugui, J. B., et al. (2025) · Diabetes Care · doi:10.2337/dc25-s010 · Cited by 339 · see citing works
Noseworthy, P. A., Attia, Z. I., Behnken, E. M., Giblon, R. E., Bews, K. A., Liu, S., Gosse, T. A., Linn, Z. D., Deng, Y., Yin, J., et al. (2022) · The Lancet · doi:10.1016/s0140-6736(22)01637-3 · Cited by 257 · see citing works
Spertus, J. A., Birmingham, M. C., Nassif, M., Damaraju, C. V., Abbate, A., Butler, J., Lanfear, D. E., Lingvay, I., Kosiborod, M. N., & Januzzi, J. L. (2022) · Nature Medicine · doi:10.1038/s41591-022-01703-8 · Cited by 245 · see citing works
10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026
American Diabetes Association Professional Practice Committee for Diabetes*, Bajaj, M., McCoy, R. G., Balapattabi, K., Bannuru, R. R., Bellini, N. J., Bennett, A. K., Beverly, E. A., Briggs Early, K., ChallaSivaKanaka, S., et al. (2026) · Diabetes Care · doi:10.2337/dc26-s010 · Cited by 107 · see citing works
- Authors
- Jones, W. S., Mulder, H., Wruck, L. M., Pencina, M. J., Kripalani, S., Muñoz, D., Crenshaw, D. L., Effron, M. B., Re, R. N., Gupta, K., Anderson, R. D., Pepine, C. J., Handberg, E. M., Manning, B. R., Jain, S. K., Girotra, S., Riley, D., DeWalt, D. A., Whittle, J., Goldberg, Y. H., Roger, V. L., Hess, R., Benziger, C. P., Farrehi, P., Zhou, L., Ford, D. E., Haynes, K., VanWormer, J. J., Knowlton, K. U., Kraschnewski, J. L., Polonsky, T. S., Fintel, D. J., Ahmad, F. S., McClay, J. C., Campbell, J. R., Bell, D. S., Fonarow, G. C., Bradley, S. M., Paranjape, A., Roe, M. T., Robertson, H. R., Curtis, L. H., Sharlow, A. G., Berdan, L. G., Hammill, B. G., Harris, D. F., Qualls, L. G., Marquis-Gravel, G., Modrow, M. F., Marcus, G. M., Carton, T. W., Nauman, E., Waitman, L. R., Kho, A. N., Shenkman, E. A., McTigue, K. M., Kaushal, R., Masoudi, F. A., Antman, E. M., Davidson, D. R., Edgley, K., Merritt, J. G., Brown, L. S., Zemon, D. N., McCormick, T. E., Alikhaani, J. D., Gregoire, K. C., Rothman, R. L., Harrington, R. A., & Hernandez, A. F.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- From 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; Albe...
- Northwestern University (US)
- ORCID
- Jones, W. Schuyler
- Mulder, Hillary
- Wruck, Lisa M.
- Pencina, Michael J.
- Kripalani, Sunil
- Effron, Mark B.
- Gupta, Kamal
- Anderson, R. David
- Pepine, Carl J.
- Handberg, Eileen M.
- Jain, Sandeep K.
- Girotra, Saket
- Riley, Danielle
- DeWalt, Darren A.
- Whittle, Jeff
- Goldberg, Ythan H.
- Roger, Veronique L.
- Hess, Rachel
- Benziger, Catherine P.
- Farrehi, Peter
- Zhou, Li
- Ford, Daniel E.
- Haynes, Kevin
- VanWormer, Jeffrey J.
- Knowlton, Kirk U.
- Kraschnewski, Jennifer L.
- Polonsky, Tamar S.
- Ahmad, Faraz S.
- McClay, James C.
- Campbell, James R.
- Bell, Douglas S.
- Fonarow, Gregg C.
- Bradley, Steven M.
- Paranjape, Anuradha
- Roe, Matthew T.
- Curtis, Lesley H.
- Sharlow, Amber G.
- Berdan, Lisa G.
- Hammill, Bradley G.
- Qualls, Laura G.
- Modrow, Madelaine F.
- Marcus, Gregory M.
- Carton, Thomas W.
- Nauman, Elizabeth
- Waitman, Lemuel R.
- Kho, Abel N.
- Shenkman, Elizabeth A.
- McTigue, Kathleen M.
- Kaushal, Rainu
- Masoudi, Frederick A.
- Antman, Elliott M.
- Merritt, James G.
- Rothman, Russell L.
- Harrington, Robert A.
- Hernandez, Adrian F.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2021-05-27
- Volume
- 384
- Issue
- 21
- Pages
- 1981-1990
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC9908069
- OpenAlex
- W3162833931
- Cited by
- 307
- References
- 13
- Citations by year
- 2026: 37 · 2025: 63 · 2024: 63 · 2023: 56 · 2022: 51 · 2021: 36
- FWCI
- 34.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- ScholarSphere (Penn State Libraries) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Patient-Centered Outcomes Research Institute (Award (ASP-1502-27029))
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Keywords
- aspirin dosing, low-dose aspirin, high-dose aspirin, atherosclerotic cardiovascular disease, major bleeding, myocardial infarction, stroke, cardiovascular mortality, secondary prevention, antiplatelet therapy, bleeding risk, hospitalization
- MeSH terms
- Assessment of Medication Adherence, Aged, Aspirin, Cardiovascular Diseases, Female, Hemorrhage, Hospitalization, Humans, Male, Middle Aged, Myocardial Infarction, Platelet Aggregation Inhibitors, Drug Monitoring, Stroke, Atherosclerosis, Medication Adherence, Secondary Prevention
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
