The ADAPTABLE Trial and Aspirin Dosing in Secondary Prevention for Patients with Coronary Artery Disease

  • Abigail Johnston
  • W. Schuyler Jones
  • Adrian F. Hernandez
New Therapies for Cardiovascular Disease (KW Mahaffey, Section Editor)
Part of the following topical collections:
  1. Topical Collection on New Therapies for Cardiovascular Disease


Coronary artery disease (CAD) is the underlying cause of death in one out of seven deaths in the USA. Aspirin therapy has been proven to decrease mortality and major adverse cardiovascular events in patients with CAD. Despite a plethora of studies showing the benefit of aspirin in secondary prevention of cardiovascular events, debate remains regarding the optimal dose due to relatively small studies that had disparate results when comparing patients taking different aspirin dosages. More recently, aspirin dosing has been thoroughly studied in the CAD population with concomitant therapy (such as P2Y12 inhibitors); however, patients in these studies were not randomized to aspirin dose. No randomized controlled trial has directly measured aspirin dosages in a population of patients with established coronary artery disease. In 2015, the Patient-Centered Outcomes Research Institute (PCORI) developed a network, called PCORnet, that includes patient-powered research networks (PPRN) and clinical data research networks (CDRN). The main objective of PCORnet is to conduct widely generalizable observational studies and clinical trials (including large, pragmatic clinical trials) at a low cost. The first clinical trial, called Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-term Effectiveness (ADAPTABLE), will randomly assign 20,000 subjects with established coronary heart disease to either low dose (81 mg) or high dose (325 mg) and should be able to finally answer which dosage of aspirin is best for patients with established cardiovascular disease.


Aspirin Coronary artery disease Secondary prevention Myocardial infarction 



American College of Cardiology Foundation


acute coronary syndrome


American Heart Association


anisoylated plasminogen streptokinase activator complex


Antiplatelet Trialists’ Collaboration


Antithrombotic Trialists’ Collaboration


coronary artery bypass graft


coronary artery disease


clinical data research networks




cardiovascular disease


dual-antiplatelet therapy


Global Use of Strategies to Open Occluded Arteries


major adverse cardiovascular event


myocardial infarction


non-ST-elevation myocardial infarction


Patient Centered Outcomes Research Institute


Practice Innovation and Clinical Excellence


patient-powered research networks


randomized controlled trial


stable ischemic heart disease


ST-elevation myocardial infarction


transient ischemic attack


Thrombolysis in Myocardial Infarction


tissue plasminogen activator


TReatment with ADP receptor iNhibitorS: Longitudinal, Assessment of Treatment Patterns and Events after Acute, Coronary Syndrome


unstable angina


Compliance with Ethics Standards

Conflict of Interest

Abigail Johnston declares that she has no conflict of interest.

W. Schuyler Jones reports research grants from Agency for Healthcare Research and Quality, AstraZeneca, American Heart Association, Boston Scientific Corporation, Bristol-Myers Squibb, and Patient-Centered Outcomes Research Institute; and honorarium/other from American College of Radiology and Daiichi Sankyo.

Adrian F. Hernandez reports research grants from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Glaxo SmithKline, Merck, and Portola Pharmaceuticals; and consulting from Amgen, AstraZeneca, Bayer, Eli Lilly, Gilead, Glaxo SmithKline, Janssen, Merck, Novartis, Ortho-McNeil, Pfizer, Pluristem Therapeutics, and MyoKardia.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


ADAPTABLE is being funded by the Patient-Centered Outcomes Research Institute. Dr. Hernandez serves as the PCORnet Coordinating Center Principal Investigator.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.•
    Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Circulation. 2015;131(4):e29–322. The most recent statistics issued by the American Heart Association indicate the high prevalence of coronary heart disease and the wide variation in aspirin treatment across the US. CrossRefPubMedGoogle Scholar
  2. 2.
    Baigent C, Blackwell L, Collins R, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373(9678):1849–60.CrossRefPubMedGoogle Scholar
  3. 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. Br Med J. 2002;324(7329):71–86.CrossRefGoogle Scholar
  4. 4.
    ISIS-2 Investigators. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Lancet. 1988;2(8607):349–60.Google Scholar
  5. 5.
    Soni A. Aspirin use among the adult U.S. noninstitutionalized population, with and without indicators of heart disease, 2005. Statistical Brief #179. Rockville: Agency for Healthcare Research and Quality; 2007.
  6. 6.
    Patrono C, Coller B, Fitzgerald GA, et al. Platelet-active drugs: the relationships among dose, effectiveness, and side effects: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(3 Suppl):234s–64s.CrossRefPubMedGoogle Scholar
  7. 7.
    Peters RJ, Mehta SR, Fox KA, et al. Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes: observations from the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) study. Circulation. 2003;108(14):1682–7.CrossRefPubMedGoogle Scholar
  8. 8.
    Aronow HD, Califf RM, Harrington RA, et al. Relation between aspirin dose, all-cause mortality, and bleeding in patients with recent cerebrovascular or coronary ischemic events (from the BRAVO Trial). Am J Cardiol. 2008;102(10):1285–90.CrossRefPubMedGoogle Scholar
  9. 9.
    Lee M, Cryer B, Feldman M. Dose effects of aspirin on gastric prostaglandins and stomach mucosal injury. Ann Intern Med. 1994;120(3):184–9.CrossRefPubMedGoogle Scholar
  10. 10.••
    Hall HM, de Lemos JA, Enriquez JR, et al. 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(5):701–7. This study shows the variation in aspirin dosing patterns across the United States in patients post- acute coronary syndrome.CrossRefPubMedGoogle Scholar
  11. 11.
    Campbell CL, Smyth S, Montalescot G, et al. Aspirin dose for the prevention of cardiovascular disease: a systematic review. JAMA. 2007;297(18):2018–24.CrossRefPubMedGoogle Scholar
  12. 12.
    Fuster V, Sweeny JM. Aspirin: a historical and contemporary therapeutic overview. Circulation. 2011;123(7):768–78.CrossRefPubMedGoogle Scholar
  13. 13.
    Antiplatelet Trialists’ Collaboration. Secondary prevention of vascular disease by prolonged antiplatelet treatment. Br Med J. 1988;296(6618):320–31.CrossRefGoogle Scholar
  14. 14.
    FitzGerald GA, Oates JA, Hawiger J, et al. Endogenous biosynthesis of prostacyclin and thromboxane and platelet function during chronic administration of aspirin in man. J Clin Invest. 1983;71(3):676–88.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Antiplatelet Trialists’ Collaboration. Collaborative overview of randomised trials of antiplatelet therapy prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Br Med J. 1994;308:81–106.CrossRefGoogle Scholar
  16. 16.
    Hoffman W, Förster W. Two year Cottbus reinfarction study with 30 mg aspirin per day. Prostaglandins Leukot Essent Fat Acids. 1991;44(3):159–69.CrossRefGoogle Scholar
  17. 17.
    Husted SE, Kraemmer Nielsen H, Krusell LR, et al. Acetylsalicylic acid 100 mg and 1000 mg daily in acute myocardial infarction suspects: a placebo-controlled trial. J Intern Med. 1989;226(5):303–10.CrossRefPubMedGoogle Scholar
  18. 18.
    Kong DF, Hasselblad V, Kandzari DE, et al. Seeking the optimal aspirin dose in acute coronary syndromes. Am J Cardiol. 2002;90(6):622–5.CrossRefPubMedGoogle Scholar
  19. 19.
    Berger JS, Brown DL, Becker RC. Low-dose aspirin in patients with stable cardiovascular disease: a meta-analysis. Am J Med. 2008;121(1):43–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Bhatt DL, Fox KAA, Hacke W, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. NEJM. 2006;354(16):1706–17.CrossRefPubMedGoogle Scholar
  21. 21.
    Steinhubl SR, Berger PB, Mann 3rd JT, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA. 2002;288(19):2411–20.CrossRefPubMedGoogle Scholar
  22. 22.
    O’Connor CM, Meese RB, McNulty S, et al. A randomized factorial trial of reperfusion strategies and aspirin dosing in acute myocardial infarction. Am J Cardiol. 1996;77(10):791–7.CrossRefPubMedGoogle Scholar
  23. 23.
    The CURRENT-OASIS 7 Investigators. Dose comparisons of clopidogrel and aspirin in acute coronary syndromes. NEJM. 2010;363(10):930–42.CrossRefGoogle Scholar
  24. 24.
    Mehta SR, Tanguay JF, Eikelboom JW, et al. Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial. Lancet. 2010;376(9748):1233–43.CrossRefPubMedGoogle Scholar
  25. 25.
    Xian Y, Wang TY, McCoy LA, et al. 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(3):174–81.Google Scholar
  26. 26.
    Kohli P, Udell JA, Murphy SA, et al. 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(3):225–32.CrossRefPubMedGoogle Scholar
  27. 27.
    Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. NEJM. 2009;361(11):1045–57.CrossRefPubMedGoogle Scholar
  28. 28.
    Ohman EM, Roe MT. Explaining the unexpected: insights from the PLATelet inhibition and clinical Outcomes (PLATO) trial comparing ticagrelor and clopidogrel. Editorial on Serebruany “Viewpoint: paradoxical excess mortality in the PLATO trial should be independently verified”. Thromb Haemost. 2011;105(5):763–5.CrossRefPubMedGoogle Scholar
  29. 29.
    Mahaffey KW, Wojdyla DM, Carroll K, et al. Ticagrelor compared with clopidogrel by geographic region in the Platelet Inhibition and Patient Outcomes (PLATO) trial. Circulation. 2011;124(5):544–54.CrossRefPubMedGoogle Scholar
  30. 30.
    The GUSTO investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med. 1993;329(10):673–82.CrossRefGoogle Scholar
  31. 31.
    Chesebro JH, Knatterud G, Roberts R, et al. Thrombolysis in Myocardial Infarction (TIMI) trial, phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge. Circulation. 1987;76(1):142–54.CrossRefPubMedGoogle Scholar
  32. 32.
    Mehran R, Rao SV, Bhatt DL, et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the bleeding academic research consortium. Circulation. 2011;123(23):2736–47.CrossRefPubMedGoogle Scholar
  33. 33.
    Fang J, George MG, Gindi RM, et al. Use of low-dose aspirin as secondary prevention of atherosclerotic cardiovascular disease in US adults (from the National Health Interview Survey, 2012). Am J Cardiol. 2015;115(7):895–900.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Perk J, De Backer G, Gohlke H, et al. European guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J. 2012;33(13):1635–701.CrossRefPubMedGoogle Scholar
  35. 35.
    Smith SC, Benjamin EJ, Bonow RO, et al. 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(22):2458–73.CrossRefPubMedGoogle Scholar
  36. 36.
    Serebruany VL. Viewpoint: paradoxical excess mortality in the PLATO trial should be independently verified. Thromb Haemost. 2011;105(5):752–9.CrossRefPubMedGoogle Scholar
  37. 37.••
    ADAPTABLE Home- Adaptable. Retrieved from This study is a large, multicenter randomized clinical trial addressing optimal aspirin dosing in secondary prevention in patients with cardiovascular disease.
  38. 38.
    Jneid H, Bhatt DL, Corti R, et al. Aspirin and clopidogrel in acute coronary syndromes: therapeutic insights from the CURE study. Arch Intern Med. 2003;163(10):1145–53.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Abigail Johnston
    • 1
    • 2
  • W. Schuyler Jones
    • 1
    • 2
  • Adrian F. Hernandez
    • 1
    • 2
  1. 1.Duke Clinical Research InstituteDuke University School of MedicineDurhamUSA
  2. 2.Department of MedicineDuke University School of MedicineDurhamUSA

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