Skip to content
  • Home
  • History
    • Introduction
    • The Aspirin Story
    • Timeline
    • Chemistry
  • Advisory Board
  • Awards
  • Conferences
  • Scientific Information
    • Guidelines
    • Disease Prevention
    • Aspirin Summaries
    • Aspirin Matters
  • News
  • Contact
Menu
  • Home
  • History
    • Introduction
    • The Aspirin Story
    • Timeline
    • Chemistry
  • Advisory Board
  • Awards
  • Conferences
  • Scientific Information
    • Guidelines
    • Disease Prevention
    • Aspirin Summaries
    • Aspirin Matters
  • News
  • Contact
Search
Close

Are US cardiologists ADAPTABLE to considering low-dose aspirin for secondary prevention?

  • July 14, 2021
Dp2

Giovanna Liuzzo and Carlo Patrono

Department of Cardiovascular and Pulmonary Sciences, Fondazione Policlinico Gemelli-IRCCS, Catholic University School of Medicine, Largo A. Gemelli 8, 00168, Rome, Italy; and Department of Pharmacology, Fondazione Policlinico Gemelli-IRCCS, Catholic University School of Medicine, Largo F. Vito 1, 00168, Rome, Italy

The results of ‘Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease’ have been published in the New England Journal of Medicine. doi:10.1056/NEJMoa2102137.

Key Points:

  • ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness), an open-label, pragmatic, random- ized, controlled trial, funded by the Patient-Centered Outcomes Research Institute, was designed to test the hypothesis that a higher aspirin dose (325 mg daily) would result in a lower risk of death from any cause, hospitalization for myocardial infarction (MI), or hospitalization for stroke (primary effectiveness endpoint) than a lower dose (81 mg daily) among patients with atherosclerotic cardiovascular disease
    (ASCVD).1 The primary safety outcome was hospitalization for major bleeding with an associated blood-product transfusion.
  • Patients with established ASCVD were identified with the use of electronic health record data at each institution; moreover, to streamline procedures and reduce costs, patients were instructed to access a Web portal to give informed consent and be notified of their aspirin reg- imen (which they were asked to purchase themselves); and all trial visits were done virtually or by telephone, with outcomes ascertained remotely and without adjudication. Over 3 years, 15 076 patients (median age, 68 years) were recruited and randomly assigned in a 1:1 ra- tio to take 325 or 81 mg of aspirin daily. About one-third had previous MI, and one-half had previous coronary revascularization proce- dures. The vast majority reported that they had been taking aspirin before enrolling in the trial; of these patients, 85% and 12% reported taking 81 and 325 mg, respectively.
  • During a median 26-month follow-up, there were no statistically significant differences between the two aspirin doses, either in the risk of the primary effectiveness endpoint [estimated percentage, 7.28% in the 81-mg group and 7.51% in the 325-mg group; hazard ratio (HR), 1.02; 95% confidence interval (CI), 0.91–1.14] or in the risk of hospitalization for major bleeding (estimated percentage, 0.63% in the 81-mg group and 0.60% in the 325-mg group; HR, 1.18; 95% CI, 0.79–1.77). Interestingly, all-cause death occurred in 315 patients (estimate at me- dian follow-up, 3.8%) in the 81-mg group and 357 patients (estimate at median follow-up, 4.4%) in the 325-mg group (HR, 0.87; 95% CI, 0.75–1.01), with time-to-event curves progressively diverging after 6 months. No heterogeneity in treatment effect was apparent among 8 prespecified sub-groups. However, aspirin discontinuation was reported by 7% of the patients assigned to the 81-mg group and 11% of those assigned to the 325-mg group, and dose switching was reported by 7% in the 81-mg group and 42% in the 325-mg group.

Comment:

While a streamlined design with greatly reduced costs is a welcome in- novation for a large, independent randomized clinical trial in the USA, lack of a pilot feasibility study and/or a pre-randomization run-in period to test tolerability of the study medications is a major weakness of the ADAPTABLE trial,1 as pointed out by Colin Baigent in the accompany- ing Editorial.2 Although asymmetrical dose switching may have biased the results toward the null, lack of a pharmacologically plausible hypothesis to justify the expected superiority of 325 vs. 81 mg of as- pirin makes the apparent equipoise between the two largely unsur- prising. In fact, previous indirect3 as well as direct4 dose comparisons failed to show superiority of a higher dose vs. a lower dose of aspirin, consistently with saturability of platelet thrombox- ane inhibition at low doses.5 The ADAPTABLE results are in line with previous knowledge about dose requirements for a full antith- rombotic effect of aspirin,6 and coherent with lack of evidence for a non-platelet mediated mechanism of action (e.g., anti-inflammatory) contributing to clinical efficacy.

Interestingly, in a post hoc subgroup analysis of ADAPTABLE based on body weight <70 or >70 kg, heavier patients had almost identical rates of events (7.1%) of the primary outcome in both dose groups.1 Previously, low doses of aspirin (75–100 mg daily) were reported as being effective in preventing vascular events only in patients weighing <70 kg, with no apparent benefit in the 80% of men and nearly 50% of all women weighing 70 kg or more.

The fact that the vast majority of the enrolled patients previously taking aspirin were taking 81 mg daily before randomization and that both aspirin discontinuation and dose switching were reported more frequently in the 325-mg group than in the 81-mg group during follow- up may well have reflected several time-related changes in patients’ and doctors’ attitudes and perceptions but is also consistent with supe- rior tolerability (particularly, gastrointestinal [GI]) of the lower dose vs. the higher dose.4 The apparent lack of a difference in the primary safety outcome of hospitalization for major bleeding should be viewed within the context of the wide statistical uncertainty surrounding the point estimate of the hazard ratio, reflecting <100 such events having been reported during the 26-month follow-up.1 In the CURRENT- OASIS 7 trial of 25 086 patients with acute coronary syndromes, there was a statistically significant increase in the incidence of major GI bleeding among patients who received higher-dose aspirin (0.4%), as compared with those who received lower-dose aspirin (0.2%;P ¼ 0.04).

We conclude that any remaining uncertainty regarding the optimal dose of aspirin for the prevention and treatment of ASCVD, that prompted the CURRENT-OASIS 74 and ADAPTABLE1 investigators to randomize over 40,000 patients with acute and chronic coronary syndromes to a lower or higher dose, should now yield to a large body of evidence1,3,4 demonstrating saturability of the antithrombotic effect of aspirin at low doses, consistent with saturability of its molecular mechanism of action and clinical pharmacology of platelet thrombox- ane inhibition.5

Conflict of interest: G.L. received grant support (to the Institution) for investigator-initiated research from American Heart Association, Italian National Health Service and Italian Minister of Education, University and Research. She is currently involved in the Research Programs of the Italian Cardiovascular Network. C.P. received consul- tant and speaker fees from Acticor Biotech, Amgen, Bayer, Eli Lilly, GlaxoSmithKline, Tremeau, and Zambon and grant support (to the Institution) for investigator-initiated research from AIFA (Italian Drug Agency), Bayer, Cancer Research UK, and European Commission; he chairs the Scientific Advisory Board of the International Aspirin Foundation.

References:

  1. Jones WS, Mulder H, Wruck LM, Pencina MJ, Kripalani S, Mu~noz D, Crenshaw DL, Effron MB, Re RN, Gupta K, Anderson RD, Pepine CJ, Handberg EM, Manning BR, Jain SK, Girotra S, Riley D, DeWalt DA, Whittle J, Goldberg YH, Roger VL, Hess R, Benziger CP, Farrehi P, Zhou L, Ford DE, Haynes K, VanWormer JJ, Knowlton KU, Kraschnewski JL, Polonsky TS, Fintel DJ, Ahmad FS, McClay JC, Campbell JR, Bell DS, Fonarow GC, Bradley SM, Paranjape A, Roe MT, Robertson HR, Curtis LH, Sharlow AG, Berdan LG, Hammill BG, Harris DF, Qualls LG, Marquis-Gravel G, Modrow MF, Marcus GM, Carton TW, Nauman E, Waitman LR, Kho AM, Shenkman EA, McTigue KM, Kaushal R, Masoudi FA, Antman EM, Davidson DR, Edgley K, Merritt JG, Brown LS, Zemon DN, McCormick TE, 3rd, Alikhaani JD, Gregoire KC, Rothman RL, Harrington RA, Hernandez AF; ADAPTABLE Team. Comparative effectiveness of aspirin dosing in cardiovascular disease. N Engl J Med 2021;384:1981–1990.
  2. Baigent C. Pragmatic trials—need for ADAPTABLE design. N Engl J Med 2021;384:2065–2066.
  3. Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324:71–86.
  4. Mehta SR, Bassand JP, Chrolavicius S, Diaz R, Eikelboom JW, Fox KA, Granger CB, Jolly S, Joyner CD, Rupprecht HJ, Widimsky P, Afzal R, Pogue J, Yusuf S; CURRENT-OASIS 7 Investigators. Dose comparisons of clopidogrel and aspirin in acute coronary syndromes. N Engl J Med 2010;363:930–942.
  5. Patrignani P, Filabozzi P, Patrono C. Selective cumulative inhibition of platelet thromboxane production by low-dose aspirin in healthy subjects. J Clin Invest 1982;69:1366–1372.
  6. Patrono C, Garc´ıa Rodr´ıguez LA, Landolfi R, Baigent C. Low-dose aspirin for the prevention of atherothrombosis. N Engl J Med 2005;353:2373–2383.
  7. Patrono C, Morais J, Baigent C, Collet JP, Fitzgerald D, Halvorsen S, Rocca B, Siegbahn A, Storey RF, Vilahur G. Antiplatelet agents for the treatment and prevention of coronary atherothrombosis. J Am Coll Cardiol 2017;70:1760–1776.
  8. Rothwell PM, Cook NR, Gaziano JM, Price JF, Belch JFF, Roncaglioni MC, Morimoto T, Mehta Z. Effects of aspirin on risks of vascular events and cancer according to bodyweight and dose: analysis of individual patient data from randomised trials. Lancet 2018;392:387–399.

SHARE THIS ARTICLE

Twitter
LinkedIn
LATEST NEWS
Drelisallurba

Aspirin Tributes : Dr Elisa Llurba

March 3, 2023
Cp Ac

Dr Andrew Chan appointed as Chair of the Scientific Advisory Board of the International Aspirin Foundation

October 19, 2022

Connect with us

Sign up to be part of the aspirin community and be the first to receive latest information.

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Have something to say about aspirin?

Contact Us Here
Footer Logo
  • Terms & Conditions
  • Branding Guidelines
  • Privacy
  • Cookie Policy
  • Disclaimer
  • Terms & Conditions
  • Branding Guidelines
  • Privacy
  • Cookie Policy
  • Disclaimer
TwitterLinkedin

Copyright © 2020 Aspirin Foundation

Website by mtc.

Have something to say about aspirin?

Please fill in the form below and we will contact you with further information.

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Djp

Daniel José Piñeiro

ASSOCIATE
Name
Daniel José Piñeiro
Academic Affiliations:
Full Professor of Medicine, Universidad de Buenos Aires, Argentina Trustee, Board of Trustees, American College of Cardiology
Professional Setting:
My academic experience includes more than 40 years as a practicing medical doctor, teacher, and researcher. I have fulfilled these appointments in settings of vital social engagement and impact, most notably at the Hospital de Clínicas “José de San Martín” of the Universidad de Buenos Aires, a public hospital with high academic recognition. Additionally, I currently hold the position of Full Professor of Medicine at that same University.
Academic Activities:
  • International Meetings Participations: 180
  • Books-Editor: 1
  • Books Chapters: 39
  • Refereed Full Articles: 118 (listed in Pubmed: 29)
  • Refereed Abstracts: 221
  • Editorial Boards: 10
Profesional Associations:
  • 2005 President, Sociedad Argentina de Cardiología.
  • 2011-2013 President, Inter-American Society of Cardiology.
  • 2011-2013 Member (ex-officio), Board of Directors, World Heart Federation
  • 2017-2018 Member (at large), Board of Directors, World Heart Federation
  • 2018-2021 Trustee, Board of Trustees, American College of Cardiology
Return to Scientific Advisory Board
Chia

John Chia

Name
John Chia MBBS (Spore), MRCP (UK), FAMS (Spore)
Academic Affiliations:

Adjunct Associate Professor DUKE-NUS Graduate Medical School,
Consultant Oncologist Curie Oncology Singapore,
Visiting Consultant National Cancer Centre Singapore.

Discipline:

Medical Oncology

Scientific Interests:
  • Aspirin as adjuvant therapy in established cancers
  • Adoptive T cell therapy and Dendritic cell vaccines in the treatment of solid tumors
  • Clinical Trial Design and Management
Declaration of Conflicts of Interest:

In the past 3 years, I have received consultant fees from Tessa Therapeutics, Aslan Pharmaceuticals, Novartis, and AstraZeneca.

I received grant support for investigator-initiated research from:

  • National Medical Research Council Singapore
  • Bayer AG

I hold shares in:  Roche, BMS, AstraZeneca, Incyte, Teva Pharmaceuticals, Trillium Therapeutics, Compugen, Arrowhead pharmaceuticals, Emergex, QuantumDx and Halozyme Therapeutics

Return to Scientific Advisory Board
Badimon

Lina Badimon

Name
Lina Badimon BSc, PharmD, PhD, FESC, FAHA
Academic Affiliations:
Director of the Cardiovascular Science Program (ICCC) at the Hospital Santa Creu and San Pau, IIB-Sant Pau; CIBER CV. Director of the Cardiovascular Research Chair of the Autonomous University of Barcelona and Director of the UNESCO Chair in Biomedical Sciences Training and Research.
Discipline:
Pharmacology, Cardiovascular Disease
Scientific Interests:
Cardio-metabolic diseases, thrombosis, atherosclerosis and ischemic heart disease
Declaration of Conflicts of Interest:

I received consultant and speakers fees from Amgen, AstraZeneca, Bayer, Lilly and Sanofi.

    Return to Scientific Advisory Board
    Ge

    Junbo Ge

    Name

    Junbo Ge

    Ge Junbo, male, was born in Wulian, Shandong province on Nov. 8, 1962. He is the member of Chinese Academy of Sciences, professor and doctoral supervisor. He received his doctor’s degree of Medicine from German Mayence University in 1993 and now works as the director for Shanghai Institute of Cardiovascular Disease and the Center for Stem Cells and Tissue Engineering, Fudan University. He is also the designate chairman of the Cardiovascular Disease Branch of Chinese Medical Association, council member of the Cardiovascular Angiography and Interventions Association, international consultant of the American Heart Association. In Dec. 2013, he was appointed as the vice president of Tongji University.

    Prof. Ge has been engaged in clinical and scientific research work of cardiovascular disease since 1987, and his research area covers the pathogenesis of coronary heart disease, early diagnosis and treatment plan optimization.

    Return to Scientific Advisory Board
    Langley

    Ruth Langley

    Name
    Ruth Langley PhD, FRCP
    Academic Affiliations:
    Professor of Oncology and Clinical Trials, MRC Programme Leader and Chair of the Cancer Group, MRC Clinical Trials Unit at UCL, honorary consultant in medical oncology at the Brighton and Sussex University Hospital.
    Discipline:
    Medical oncologist; trialist
    Scientific Interests:
    • Aspirin
    • Gastro-oesophageal malignancy
    • Transdermal oestrogen in the treatment of prostate cancer
    • Trials methodology
    Declaration of Conflicts of Interest:
    Has received honorarium from Bayer
    Return to Scientific Advisory Board
    Chan

    Andrew T Chan

    Name
    Andrew T. Chan MD, MPH
    Academic Affiliations:
    Chief, Clinical and Translational Epidemiology Unit, Vice Chair, Division of Gastroenterology, Massachusetts General Hospital, Boston, Co-leader, Cancer Epidemiology Program, Dana-Farber/Harvard Cancer Center, Boston.
    Discipline:
    Gastroenterology
    Scientific Interests:
    • The role of aspirin in the prevention of colorectal cancer and other cancers
    • The role of the gut microbiome in colorectal cancer and other chronic gastrointestinal diseases, including inflammatory bowel disease and diverticulitis
    • The role of diet and lifestyle in colorectal cancer and other chronic gastrointestinal cancers
    Declaration of Conflicts of Interest:

    AACR Honors Dr. Andrew T. Chan With 2019 AACR-Waun Ki Hong Award

    Click here to find the press release.

    I received consultant Bayer and Pfizer, Inc.

    I received grant support for investigator-initiated research from:

    • National Institutes of Health
    • National Cancer Institute
    • Crohn’s and Colitis Foundation
    • Bayer AG
    Return to Scientific Advisory Board
    Gaziano

    Mike Gaziano

    Name
    J Michael Gaziano MD, MPH
    Academic Affiliations:

    Professor of Medicine, Harvard Medical School; Chief Division of Aging, Brigham and Women’s Hospital; Director of Preventive Cardiology and Director of Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System.
    Discipline: Cardiology and Epidemiology

    Scientific Interests:
    I am a chronic disease epidemiologist with a particular interest in the roles that individual lifestyle choices (diet, exercise, smoking), metabolic factors (obesity, high cholesterol, and hypertension), and biochemical and genetic markers play on the risk of cardiovascular disease and other chronic illnesses. Also, of interest is the impact that vascular disease has on other organ systems, including cognitive dysfunction and renal disease. I have an interest in the design of large-scale trials and observational studies nested in large health care systems using big data analytic techniques.
    Declaration of Conflicts of Interest:

    I received consultant and speaker fees Bayer.

    I received grant support as a principal investigator or co-investigator for research from the VA, DOD, NIH, Merck and Kowa.

    Return to Scientific Advisory Board
    Pierre A Web Photo

    Pierre Amarenco

    Name

    Pierre Amarenco, MD, FAHA, FAAN

    Academic Affiliations:
    • Professor of Neurology at Paris-Diderot Sorbonne University 
    • Chairman of the Department of Neurology and Stroke Center; Bichat University Hospital
    • Co-Director INSERM Unit-698 “Clinical Research in Atherothrombosis”
    Discipline:

    Neurology and Vascular Neurology

    Scientific Interests:
    • Understanding and preventing stroke and vascular diseases
    • Clinical trials in prevention of vascular diseases
    • Carotid intima-media thickness studies
    • Lipid trials: prevention and therapeutic –protective- evaluation
    Declaration of Conflicts of Interest:

    N/A

    Return to Scientific Advisory Board
    CarloPatrono

    Carlo Patrono

    CHAIR
    Name
    Carlo Patrono MD, FESC, FRCP
    Academic Affiliations:
    Adjunct Professor of Pharmacology at the Catholic University School of Medicine in Rome (Italy) and at the Perelman School of Medicine of the University of Pennsylvania in Philadelphia (USA).
    Discipline:
    Clinical Pharmacology
    Scientific Interests:
    • Studying platelet activation and inhibition in diabetes mellitus
    • Studying platelet activation and inhibition in myeloproliferative neoplasms
    • Investigating the mechanism of action of low-dose aspirin in preventing colorectal cancer
    Declaration of Conflicts of Interest:

    I received consultant and speakers fees from Acticor Biotech,  Amgen,  Bayer, GlaxoSmithKline,  Tremeau,  Zambon.

    I received grant support for investigator-initiated research from:

    • AIFA (Italian Drug Agency)
    • Bayer AG
    • Cancer Research UK
    • European Commission, FP6 and FP7 Programmes

      Return to Scientific Advisory Board

      Have something to say about aspirin?

      We would like to hear from you and have a chat, and maybe feature you on our podcast. Please fill in the form below and we will contact you with further information.

      This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.