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Contemporary Reflections on the Safety of Long-Term Aspirin Treatment for the Secondary Prevention of Cardiovascular Disease

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Abstract

Aspirin has been the cornerstone of therapy for the secondary prevention treatment of patients with cardiovascular disease since landmark trials were completed in the late 1970s and early 1980s that demonstrated the efficacy of aspirin for reducing the risk of ischemic events. Notwithstanding the consistent benefits demonstrated with aspirin for both acute and chronic cardiovascular disease, there are a number of toxicities associated with aspirin that have been showcased by recent long-term clinical trials that have included an aspirin monotherapy arm. As an inhibitor of cyclooxygenase (COX), aspirin impairs gastric mucosal protective mechanisms. Previous trials have shown that up to 15–20 % of patients developed gastrointestinal symptoms with aspirin monotherapy, and approximately 1 % of patients per year had a clinically significant bleeding event, including 1 in 1000 patients who suffered an intracranial or fatal bleed. These risks have been shown to be compounded for patients with acute coronary syndromes (ACS) and those undergoing percutaneous coronary intervention (PCI) who are also treated with other antithrombotic agents during the acute care/procedural period, as well as for an extended time period afterwards. Given observations of substantial increases in bleeding rates from many prior long-term clinical trials that have evaluated aspirin together with other oral platelet inhibitors or oral anticoagulants, the focus of contemporary research has pivoted towards tailored antithrombotic regimens that attempt to either shorten the duration of exposure to aspirin or replace aspirin with an alternative antithrombotic agent. While these shifts are occurring, the safety profile of aspirin when used for the secondary prevention treatment of patients with established cardiovascular disease deserves further consideration.

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References

  1. Blackwell DL, Lucas J, Clarke TC. Summary health statistics for U.S. adults: National Health Interview Survey, 2012. Vital Health Stat. 2014;10(260):1–161.

    Google Scholar 

  2. Heidenreich PA, Trogdon JG, Khavjou OA, Butler J, Dracup K, Ezekowitz MD, et al. Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association. Circulation. 2011;123(8):933–44.

    Article  PubMed  Google Scholar 

  3. Fuster V, Sweeny JM. Aspirin: a historical and contemporary therapeutic overview. Circulation. 2011;123(7):768–78.

    Article  PubMed  Google Scholar 

  4. Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto 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.

    Article  PubMed  Google Scholar 

  5. 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(7329):71–86.

    Article  Google Scholar 

  6. Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, Budaj A, et al. 2013 ESC guidelines on the management of stable coronary artery disease. Eur Heart J. 2013;34(38):2949–3003.

    Article  PubMed  Google Scholar 

  7. Fihn SD, Gardin JM, Abrams J, Berra K, Blankenship JC, Douglas PS, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2012;60(24):e44–164.

    Article  PubMed  Google Scholar 

  8. Perk J, De Backer G, Gohlke H, Graham I, Reiner Ž, Verschuren M, et al. European guidelines on cardiovascular disease prevention in clinical practice (version 2012). Eur Heart J. 2012;33(13):1635–701.

    Article  CAS  PubMed  Google Scholar 

  9. Wolff T, Miller T, Ko S. Aspirin for the primary prevention of cardiovascular events: an update of the evidence for the US Preventive Services Task Force. Ann Intern Med. 2009;150(6):405–10.

    Article  PubMed  Google Scholar 

  10. U.S. Preventive Service Task Force. Draft recommendation statement: aspirin to prevent cardiovascular disease and cancer. September 2015. Available at: http://www.uspreventiveservicestaskforce.org/Page/Document/draft-recommendation-statement/aspirin-to-prevent-cardiovascular-disease-and-cancer. Accessed 3 Sept 2016.

  11. Amsterdam E, Wenger N. 2014 ACC/AHA guideline for the management of patients with non–ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines: executive summary. J Am Coll Cardiol. 2014;64:2645–87.

    Article  Google Scholar 

  12. O’Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;61(4):e78–140.

    Article  PubMed  Google Scholar 

  13. Roffi M, Patrono C, Collet J-P, Mueller C, Valgimigli M, Andreotti F, et al. 2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016;37(3):267–315.

    Article  PubMed  Google Scholar 

  14. Bonaca MP, Bhatt DL, Cohen M, Steg PG, Storey RF, Jensen EC, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015;372(19):1791–800.

    Article  PubMed  Google Scholar 

  15. Mauri L, Kereiakes DJ, Yeh RW, Driscoll-Shempp P, Cutlip DE, Steg PG, et al. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med. 2014;371(23):2155–66.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Bayer. Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease (COMPASS). [Clinicaltrials.gov identifier NCT01776424]. US National Institutes of Health, ClinicalTrials.gov. Available at: https://clinicaltrials.gov/show/NCT01776424. Accessed 10 Mar 2016.

  17. Vranckx P, Valgimigli M, Windecker S, Steg P, Hamm C, Jüni P, et al. Long-term ticagrelor monotherapy versus standard dual antiplatelet therapy followed by aspirin monotherapy in patients undergoing biolimus-eluting stent implantation: rationale and design of the GLOBAL LEADERS trial. EuroIntervention. 2015;11(7).

  18. Janssen Research & Development LLC. A study to compare the safety of rivaroxaban versus acetylsalicylic acid in addition to either clopidogrel or ticagrelor therapy in participants with acute coronary syndrome (GEMINI ACS 1). [ClinicalTrials.gov identifier NCT02293395]. US National Institutes of Health, Clinicaltrials.gov. Available at: https://clinicaltrials.gov/show/NCT02293395. Accessed 10 Mar 2016.

  19. Gibson CM, Mehran R, Bode C, Halperin J, Verheugt F, Wildgoose P, et al. An open-label, randomized, controlled, multicenter study exploring two treatment strategies of rivaroxaban and a dose-adjusted oral vitamin k antagonist treatment strategy in subjects with atrial fibrillation who undergo percutaneous coronary intervention (PIONEER AF-PCI). Amn Heart J. 2015;169(4):472–8.e5.

  20. Boehringer Ingelheim. Evaluation of dual therapy with dabigatran vs. triple therapy with warfarin in patients with AF that undergo a PCI with stenting (REDUAL-PCI). [ClinicalTrials.gov identifier NCT02164864]. US National Institutes of Health, ClinicalTrials.gov. Available at: https://clinicaltrials.gov/show/NCT02164864. Accessed 10 Mar 2016.

  21. Bristol-Myers Squibb. Study apixaban to vitamin K antagonist for the prevention of stroke or systemic embolism and bleeding in patients with non-valvular atrial fibrillation and acute coronary syndrome/percutaneous coronary intervention [ClinicalTrials.gov identifier NCT02415400. US National Institutes of Health, Clinicaltrials.gov. Available at: https://clinicaltrials.gov/show/NCT02415400. Accessed 10 Mar 2016.

  22. Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971;231(25):232–5.

    Article  CAS  PubMed  Google Scholar 

  23. Vane J, Botting R. The mechanism of action of aspirin. Thromb Res. 2003;110(5):255–8.

    Article  CAS  PubMed  Google Scholar 

  24. Topper JN, Cai J, Falb D, Gimbrone MA. Identification of vascular endothelial genes differentially responsive to fluid mechanical stimuli: cyclooxygenase-2, manganese superoxide dismutase, and endothelial cell nitric oxide synthase are selectively up-regulated by steady laminar shear stress. Proc Natl Acad Sci. 1996;93(19):10417–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Pierucci A, Simonetti BM, Pecci G, Mavrikakis G, Feriozzi S, Cinotti GA, et al. Improvement of renal function with selective thromboxane antagonism in lupus nephritis. N Engl J Med. 1989;320(7):421–5.

    Article  CAS  PubMed  Google Scholar 

  26. Patrono C, Baigent C, Hirsh J, Roth G. Antiplatelet drugs: American College of Chest Physicians evidence-based clinical practice guidelines. Chest J. 2008;133(6 Suppl):199S–233S.

    Article  CAS  Google Scholar 

  27. Roth G, Majerus PW. The mechanism of the effect of aspirin on human platelets. I: acetylation of a particulate fraction protein. J Clin Invest. 1975;56(3):624.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Patrono C, Ciabattoni G, Patrignani P, Pugliese F, Filabozzi P, Catella F, et al. Clinical pharmacology of platelet cyclooxygenase inhibition. Circulation. 1985;72(6):1177–84.

    Article  CAS  PubMed  Google Scholar 

  29. Cipollone F, Patrignani P, Greco A, Panara MR, Padovano R, Cuccurullo F, et al. Differential suppression of thromboxane biosynthesis by indobufen and aspirin in patients with unstable angina. Circulation. 1997;96(4):1109–16.

    Article  CAS  PubMed  Google Scholar 

  30. Bala M, Chin CN, Logan AT, Amin T, Marnett LJ, Boutaud O, et al. Acetylation of prostaglandin H2 synthases by aspirin is inhibited by redox cycling of the peroxidase. Biochem Pharmacol. 2008;75(7):1472–81.

    Article  CAS  PubMed  Google Scholar 

  31. Patrono C, García Rodríguez LA, Landolfi R, Baigent C. Low-dose aspirin for the prevention of atherothrombosis. N Engl J Med. 2005;353(22):2373–83.

    Article  CAS  PubMed  Google Scholar 

  32. Ungprasert P, Cheungpasitporn W, Crowson CS, Matteson EL. Individual non-steroidal anti-inflammatory drugs and risk of acute kidney injury: a systematic review and meta-analysis of observational studies. Eur J Intern Med. 2015;26(4):285–91.

    Article  CAS  PubMed  Google Scholar 

  33. Trelle S, Reichenbach S, Wandel S, Hildebrand P, Tschannen B, Villiger PM, et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ. 2011;342:c7086.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Voora D, Ortel TL, Lucas JE, Chi J-T, Becker RC, Ginsburg GS. Time-dependent changes in non-COX-1-dependent platelet function with daily aspirin therapy. J Thromb Thrombolysis. 2012;33(3):246–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Gislason GH, Jacobsen S, Rasmussen JN, Rasmussen S, Buch P, Friberg J, et al. Risk of death or reinfarction associated with the use of selective cyclooxygenase-2 inhibitors and nonselective nonsteroidal antiinflammatory drugs after acute myocardial infarction. Circulation. 2006;113(25):2906–13.

    Article  CAS  PubMed  Google Scholar 

  36. FitzGerald GA. Coxibs and cardiovascular disease. N Engl J Med. 2004;351(17):1709–11.

    Article  CAS  PubMed  Google Scholar 

  37. Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med. 1999;340(24):1888–99.

    Article  CAS  PubMed  Google Scholar 

  38. Lanza FL, Royer GL Jr, Nelson RS. Endoscopic evaluation of the effects of aspirin, buffered aspirin, and enteric-coated aspirin on gastric and duodenal mucosa. N Engl J Med. 1980;303(3):136–8.

    Article  CAS  PubMed  Google Scholar 

  39. Hansen ML, Sorensen R, Clausen MT, Fog-Petersen ML, Raunso J, Gadsboll N, et al. Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Intern Med. 2010;170(16):1433–41.

    Article  CAS  PubMed  Google Scholar 

  40. De Berardis G, Lucisano G, D’Ettorre A, Pellegrini F, Lepore V, Tognoni G, et al. Association of aspirin use with major bleeding in patients with and without diabetes. JAMA. 2012;307(21):2286–94.

    Article  PubMed  Google Scholar 

  41. De Abajo FJ. Association between aspirin and upper gastrointestinal complications: systematic review of epidemiologic studies. Br J Clin Pharmacol. 2001;52(5):563–71.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Rajan JP, Wineinger NE, Stevenson DD, White AA. Prevalence of aspirin-exacerbated respiratory disease among asthmatic patients: a meta-analysis of the literature. J Allergy Clin Immunol. 2015;135(3):676–81.e1.

  43. LaPointe NMA, Kramer JM, DeLong ER, Ostbye T, Hammill BG, Muhlbaier LH, et al. Patient-reported frequency of taking aspirin in a population with coronary artery disease. Am J Cardiol. 2002;89(9):1042–6.

    Article  Google Scholar 

  44. Niżankowska-Mogilnicka E, Bochenek G, Mastalerz L, Świerczyńska M, Picado C, Scadding G, et al. EAACI/GA2LEN guideline: aspirin provocation tests for diagnosis of aspirin hypersensitivity. Allergy. 2007;62(10):1111–8.

    Article  PubMed  Google Scholar 

  45. Córdoba-Soriano JG, Corbí-Pascual M, López-Neyra I, Navarro-Cuartero J, Hidalgo-Olivares V, Barrionuevo-Sánchez MI, et al. Early aspirin desensitization in unstable patients with acute coronary syndrome: short and long-term efficacy and safety. Eur Heart J Acute Cardiovasc Care 2015 (Epub 20 Nov 2015:2048872615618509).

  46. Elwood PC, Cochrane AL, Burr ML, Sweetnam P, Williams G, Welsby E, et al. A randomized controlled trial of acetyl salicyclic acid in the secondary prevention of mortality from myocardial infarction. Br Med J. 1974;1(5905):436.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Elwood PC, Sweetnam P. Aspirin and secondary mortality after myocardial infarction. Lancet. 1979;314(8156):1313–5.

    Article  Google Scholar 

  48. Aspirin in coronary heart disease. The Coronary Drug Project Research Group. J Chronic Dis. 1976;29(10):625–42.

  49. Schoenberger M. A randomized, controlled trialof aspirin in persons recovered from myocardial infarction. JAMA. 1980;243:661–9.

    Article  Google Scholar 

  50. Krol W. Persantine and aspirin in coronary heart disease. Circulation. 1980;62(3):449–61.

    Article  Google Scholar 

  51. Breddin K, Loew D, Lechner K, Oberla K, Walter E. The German-Austrian aspirin trial: a comparison of acetylsalicylic acid, placebo and phenprocoumon in secondary prevention of myocardial infarction. On behalf of the German-Austrian Study Group. Circulation. 1980;62(6 Pt 2):V63–72.

  52. McQuaid KR, Laine L. Systematic review and meta-analysis of adverse events of low-dose aspirin and clopidogrel in randomized controlled trials. Am J Med. 2006;119(8):624–38.

    Article  CAS  PubMed  Google Scholar 

  53. Juul-Moller S, Edvardsson N, Sorensen S, Jahnmatz B, Rosén A, Omblus R. Double-blind trial of aspirin in primary prevention of myocardial infarction in patients with stable chronic angina pectoris. Lancet. 1992;340(8833):1421–5.

    Article  CAS  PubMed  Google Scholar 

  54. Randomised double-blind trial of fixed low-dose warfarin with aspirin after myocardial infarction. Coumadin Aspirin Reinfarction Study (CARS) Investigators. Lancet. 1997;350(9075):389–96.

  55. Fiore LD, Ezekowitz MD, Brophy MT, Lu D, Sacco J, Peduzzi P. Department of Veterans Affairs Cooperative Studies Program clinical trial comparing combined warfarin and aspirin with aspirin alone in survivors of acute myocardial infarction: primary results of the CHAMP study. Circulation. 2002;105(5):557–63.

    Article  CAS  PubMed  Google Scholar 

  56. Hurlen M, Abdelnoor M, Smith P, Erikssen J, Arnesen H. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med. 2002;347(13):969–74.

    Article  CAS  PubMed  Google Scholar 

  57. van Es RF, Jonker JJ, Verheugt FW, Deckers JW, Grobbee DE. Aspirin and coumadin after acute coronary syndromes (the ASPECT-2 study): a randomised controlled trial. Lancet. 2002;360(9327):109–13.

    Article  PubMed  Google Scholar 

  58. O’Neill WW, Serruys P, Knudtson M, van Es G-A, Timmis GC, van der Zwaan C, et al. Long-term treatment with a platelet glycoprotein-receptor antagonist after percutaneous coronary revascularization. N Engl J Med. 2000;342(18):1316–24.

    Article  PubMed  Google Scholar 

  59. Comparison of sibrafiban with aspirin for prevention of cardiovascular events after acute coronary syndromes: a randomised trial. The SYMPHONY Investigators. Sibrafiban versus Aspirin to Yield Maximum Protection from Ischemic Heart Events Post-acute Coronary Syndromes. Lancet. 2000;355(9201):337–45.

  60. Yusuf S, Fox K, Tognoni G, Mehta S, Chrolavicius S, Keltai M, et al. Effects of clopidogrel in addition to aspirin in patients with acutecoronary syndromes without ST-segment elevation. N Engl J Med. 2001;345(7):494–502.

    Article  CAS  PubMed  Google Scholar 

  61. Cannon CP, McCabe CH, Wilcox RG, Langer A, Caspi A, Berink P, et al. Oral glycoprotein IIb/IIIa inhibition with orbofiban in patients with unstable coronary syndromes (OPUS-TIMI 16) trial. Circulation. 2000;102(2):149–56.

    Article  CAS  PubMed  Google Scholar 

  62. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet. 1996;348(9038):1329–39.

    Article  Google Scholar 

  63. Steinhubl SR, Berger PB, Mann JT III, Fry ET, DeLago A, Wilmer C, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA. 2002;288(19):2411–20.

    Article  CAS  PubMed  Google Scholar 

  64. Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006;354(16):1706–17.

    Article  CAS  PubMed  Google Scholar 

  65. Pfisterer M, Brunner-La Rocca HP, Buser PT, Rickenbacher P, Hunziker P, Mueller C, et al. Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents: an observational study of drug-eluting versus bare-metal stents. J Am Coll Cardiol. 2006;48(12):2584–91.

    Article  CAS  PubMed  Google Scholar 

  66. Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol. 2011;58(24):e44–122.

    Article  PubMed  Google Scholar 

  67. Windecker S, Kolh P, Alfonso F, Collet J-P, Cremer J, Falk V, et al. 2014 ESC/EACTS guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2014;35(37):2541–619.

    Article  PubMed  Google Scholar 

  68. Hennekens C. Final report on the aspirin component of the ongoing Physicians Health Study. N Engl J Med. 1989;321(3):129–35.

    Article  Google Scholar 

  69. Savage MP, Goldberg S, Bove AA, Deutsch E, Vetrovec G, Macdonald RG, et al. Effect of thromboxane A2 blockade on clinical outcome and restenosis after successful coronary angioplasty: multi-hospital eastern atlantic restenosis trial (M-HEART II). Circulation. 1995;92(11):3194–200.

    Article  CAS  PubMed  Google Scholar 

  70. Serruys PW, Rutsch W, Heyndrickx GR, Danchin N, Mast E, Wijns W, et al. Prevention of restenosis after percutaneous transluminal coronary angioplasty with thromboxane A2-receptor blockade. A randomized, double-blind, placebo-controlled trial. Coronary Artery Restenosis Prevention on Repeated Thromboxane-Antagonism Study (CARPORT). Circulation. 1991;84(4):1568–80.

    Article  CAS  PubMed  Google Scholar 

  71. Hess CN, Peterson ED, Peng SA, de Lemos JA, Fosbol EL, Thomas L, et al. Use and outcomes of triple therapy among older patients with acute myocardial infarction and atrial fibrillation. J Am Coll Cardiol. 2015;66(6):616–27.

    Article  PubMed  Google Scholar 

  72. Dewilde WJ, Oirbans T, Verheugt FW, Kelder JC, De Smet BJ, Herrman J-P, et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet. 2013;381(9872):1107–15.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Matthew T. Roe.

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Alexander Fanaroff has no conflicts of interest that are directly related to the content of this manuscript. Matthew Roe reports receiving research funding from Eli Lilly, Sanofi–Aventis, Daiichi Sanko, Janssen Pharmaceuticals, Ferring Pharmaceuticals, American College of Cardiology, American Heart Association, and the Familial Hypercholesterolemia Foundation; and reports receiving consulting fees or honoraria from PriMed, Astra Zeneca, Boehringer–Ingelheim, Merck, Amgen, Myokardia, Eli Lilly, and Elsevier Publishers.

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Fanaroff, A.C., Roe, M.T. Contemporary Reflections on the Safety of Long-Term Aspirin Treatment for the Secondary Prevention of Cardiovascular Disease. Drug Saf 39, 715–727 (2016). https://doi.org/10.1007/s40264-016-0421-1

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