Aspirin in the primary prevention of cardiovascular disease and cancer
- Frederick A Spencer, MD
Frederick A Spencer, MD
- Professor of Medicine
- McMaster University
- Gordon Guyatt, MD
Gordon Guyatt, MD
- Professor of Clinical Epidemiology and Biostatistics and Medicine
- McMaster University
- Charles H Hennekens, MD, DrPH
Charles H Hennekens, MD, DrPH
- First Sir Richard Doll Professor & Senior Academic Advisor to the Dean, Charles E. Schmidt College of Medicine, Florida Atlantic University
- Clinical Professor, Nova Southeastern University
- Voluntary Professor, University of Miami Miller School of Medicine, Meharry Medical College, and Baylor Colle
- Section Editors
- Joann G Elmore, MD, MPH
Joann G Elmore, MD, MPH
- Editor-in-Chief — Primary Care (Adult)
- Section Editor — General Medicine
- Professor of Medicine, Adjunct Professor of Epidemiology
- University of Washington School of Medicine
- Christopher P Cannon, MD
Christopher P Cannon, MD
- Section Editor — Coronary Heart Disease
- Professor of Medicine
- Harvard Medical School
- Deputy Editors
- Howard Libman, MD
Howard Libman, MD
- Deputy Editor — Primary Care (Adult)
- Professor of Medicine, Emeritus
- Harvard Medical School
- Gordon M Saperia, MD, FACC
Gordon M Saperia, MD, FACC
- Senior Deputy Editor — UpToDate
- Deputy Editor — Cardiovascular Medicine
- Assistant Professor of Medicine
- Tufts University School of Medicine
Cardiovascular disease (CVD) and cancer are the leading causes of morbidity and mortality worldwide, representing 24 and 13 percent of all deaths, respectively [1,2]. Aspirin produces statistically significant and important reductions in CVD morbidity and mortality among survivors of a wide range of occlusive CVD events, including subsequent coronary heart disease, especially myocardial infarction, stroke, and CVD death. In secondary prevention, the absolute benefits on occlusive events are far greater than the absolute risks of major bleeding. In primary prevention, however, among apparently healthy people, the benefit-to-risk ratio is less clear due, at least in part, to the paucity of randomized evidence among the moderate- to high-risk subjects most likely to achieve a net benefit.
While the benefits of aspirin on CVD have been known for decades, more recent randomized evidence has suggested a benefit on colorectal cancer and possibly total cancer deaths as well as on the development of other cancers. These findings may impact the threshold for the prescription of aspirin by health care professionals and the wishes of primary prevention subjects.
This topic summarizes the evidence regarding the benefits and risks of aspirin for primary prevention of CVD and cancer. We believe the utilization of aspirin, as for any over-the-counter drug used long term, should be an individual clinical and shared decision between the health care professional and each of his or her patients that carefully weighs all the absolute benefits against all the absolute risks [3-5].
Discussion of the role of aspirin in secondary prevention of CVD is presented separately. The role of nonsteroidal anti-inflammatory drugs and aspirin in the prevention of colorectal cancer (exclusive of CVD) is discussed separately as well. (See "NSAIDs (including aspirin): Role in prevention of colorectal cancer" and "Aspirin for the secondary prevention of atherosclerotic cardiovascular disease".)
MECHANISMS OF ACTION
Cardiovascular disease — Aspirin at all clinically relevant doses produces a clinically relevant antiplatelet effect by irreversibly acetylating the active site of cyclooxygenase-1 (COX-1), which is required for the production of thromboxane A2, a powerful promoter of aggregation. These findings are achieved by daily doses of 75 mg (and higher) or perhaps doses as low as 30 mg. Higher doses of aspirin also inhibit COX-2, which blocks prostaglandin production leading to analgesic and antipyretic effects. Although other mechanisms have been proposed (eg, an antiinflammatory effect), the antiplatelet effect seems sufficient to explain the observed statistically significant and clinically important benefits of aspirin on CVD. (See "Aspirin: Mechanism of action, major toxicities, and use in rheumatic diseases" and "Platelet biology" and "The role of the vulnerable plaque in acute coronary syndromes".)
- The top 10 causes of death. World Health Organization; 2011. http://www.who.int/mediacentre/factsheets/fs310/en/index.html (Accessed on October 27, 2011).
- World Health Organization. Cancer Fact Sheet. Updated Febuary 2012. Available at: http://www.who.int/mediacentre/factsheets/fs297/en (Accessed on October 24, 2012).
- Kaiser J. Will an aspirin a day keep cancer away? Science 2012; 337:1471.
- Chan AT, Cook NR. Are we ready to recommend aspirin for cancer prevention? Lancet 2012; 379:1569.
- Baigent C. Aspirin for Disease Prevention: Public Policy or Personal Choice? Ann Intern Med 2016; 164:846.
- Liao X, Lochhead P, Nishihara R, et al. Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival. N Engl J Med 2012; 367:1596.
- Dannenberg AJ, Lippman SM, Mann JR, et al. Cyclooxygenase-2 and epidermal growth factor receptor: pharmacologic targets for chemoprevention. J Clin Oncol 2005; 23:254.
- Guirguis-Blake JM, Evans CV, Senger CA, et al. Aspirin for the Primary Prevention of Cardiovascular Events: A Systematic Evidence Review for the U.S. Preventive Services Task Force. Ann Intern Med 2016; 164:804.
- Seshasai SR, Wijesuriya S, Sivakumaran R, et al. Effect of aspirin on vascular and nonvascular outcomes: meta-analysis of randomized controlled trials. Arch Intern Med 2012; 172:209.
- Antithrombotic Trialists' (ATT) Collaboration, Baigent C, Blackwell L, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009; 373:1849.
- Raju N, Sobieraj-Teague M, Hirsh J, et al. Effect of aspirin on mortality in the primary prevention of cardiovascular disease. Am J Med 2011; 124:621.
- Bartolucci AA, Tendera M, Howard G. Meta-analysis of multiple primary prevention trials of cardiovascular events using aspirin. Am J Cardiol 2011; 107:1796.
- Steering Committee of the Physicians' Health Study Research Group. Final report on the aspirin component of the ongoing Physicians' Health Study. N Engl J Med 1989; 321:129.
- Cook NR, Lee IM, Gaziano JM, et al. Low-dose aspirin in the primary prevention of cancer: the Women's Health Study: a randomized controlled trial. JAMA 2005; 294:47.
- Flossmann E, Rothwell PM, British Doctors Aspirin Trial and the UK-TIA Aspirin Trial. Effect of aspirin on long-term risk of colorectal cancer: consistent evidence from randomised and observational studies. Lancet 2007; 369:1603.
- Peto R, Gray R, Collins R, et al. Randomised trial of prophylactic daily aspirin in British male doctors. Br Med J (Clin Res Ed) 1988; 296:313.
- Chubak J, Kamineni A, Buist DSM et al. Aspirin use for the prevention of colorectal cancer: an updated systematic evidence review for tthe U.S. Preventive Services Task Force. Report No.: 15-05228-EF-1, U.S. Preventive Services Task Force.
- Cook NR, Lee IM, Zhang SM, et al. Alternate-day, low-dose aspirin and cancer risk: long-term observational follow-up of a randomized trial. Ann Intern Med 2013; 159:77.
- Rothwell PM, Wilson M, Elwin CE, et al. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet 2010; 376:1741.
- Thrombosis prevention trial: randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk. The Medical Research Council's General Practice Research Framework. Lancet 1998; 351:233.
- Swedish Aspirin Low-Dose Trial (SALT) of 75 mg aspirin as secondary prophylaxis after cerebrovascular ischaemic events. The SALT Collaborative Group. Lancet 1991; 338:1345.
- Farrell B, Godwin J, Richards S, Warlow C. The United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: final results. J Neurol Neurosurg Psychiatry 1991; 54:1044.
- Rothwell PM, Fowkes FG, Belch JF, et al. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet 2011; 377:31.
- Algra AM, Rothwell PM. Effects of regular aspirin on long-term cancer incidence and metastasis: a systematic comparison of evidence from observational studies versus randomised trials. Lancet Oncol 2012; 13:518.
- Rothwell PM, Price JF, Fowkes FG, et al. Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials. Lancet 2012; 379:1602.
- Whitlock EP, Williams SB, Burda BU, et al. Aspirin Use in Adults: Cancer, All-Cause Mortality, and Harms: A Systematic Evidence Review for the U.S. Preventive Services Task Force [Internet]. Report No.: 13-05193-EF-1, U.S. Preventive Services Task Force Evidence Syntheses, formerly Systematic Evidence Reviews; Agency for Healthcare Research and Quality (US), Rockville, MD 2015.
- Rothwell PM, Wilson M, Price JF, et al. Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. Lancet 2012; 379:1591.
- Sutcliffe P, Connock M, Gurung T, et al. Aspirin for prophylactic use in the primary prevention of cardiovascular disease and cancer: a systematic review and overview of reviews. Health Technol Assess 2013; 17:1.
- Vandvik PO, Lincoff AM, Gore JM, et al. Primary and secondary prevention of cardiovascular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e637S.
- Whitlock EP, Burda BU, Williams SB, et al. Bleeding Risks With Aspirin Use for Primary Prevention in Adults: A Systematic Review for the U.S. Preventive Services Task Force. Ann Intern Med 2016; 164:826.
- Stevenson DD. Aspirin and NSAID sensitivity. Immunol Allergy Clin North Am 2004; 24:491.
- Jenkins C, Costello J, Hodge L. Systematic review of prevalence of aspirin induced asthma and its implications for clinical practice. BMJ 2004; 328:434.
- Grattan CE. Aspirin sensitivity and urticaria. Clin Exp Dermatol 2003; 28:123.
- 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.
- Chan AT, Giovannucci EL, Schernhammer ES, et al. A prospective study of aspirin use and the risk for colorectal adenoma. Ann Intern Med 2004; 140:157.
- Chan AT, Giovannucci EL, Meyerhardt JA, et al. Aspirin dose and duration of use and risk of colorectal cancer in men. Gastroenterology 2008; 134:21.
- Serebruany VL, Steinhubl SR, Berger PB, et al. Analysis of risk of bleeding complications after different doses of aspirin in 192,036 patients enrolled in 31 randomized controlled trials. Am J Cardiol 2005; 95:1218.
- Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014; 63:2935.
- Cuzick J, Thorat MA, Bosetti C, et al. Estimates of benefits and harms of prophylactic use of aspirin in the general population. Ann Oncol 2015; 26:47.
- US Preventive Services Task Force. Aspirin for the prevention of cardiovascular disease: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2009; 150:396.
- Wolff T, Miller T, Ko S. Aspirin for the primary prevention of cardiovascular events: an update of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2009; 150:405.
- You JJ, Singer DE, Howard PA, et al. Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e531S.
- 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; 33:1635.
- MECHANISMS OF ACTION
- Cardiovascular disease
- POTENTIAL BENEFITS
- Prevention of CVD events
- Prevention of cancer
- - Colorectal cancer
- Colorectal cancer mortality
- - Other cancers (incidence and mortality)
- Reducing all-cause mortality
- Summary of benefits
- ADVERSE EFFECTS
- Aspirin sensitivity
- Prevention of CVD events
- Prevention of cancer events
- ASSESSING BENEFITS AND RISKS
- Individualizing decisions
- OUR APPROACH
- RECOMMENDATIONS OF OTHERS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS