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Cardiovascular and upper gastrointestinal bleeding consequences of low-dose acetylsalicylic acid discontinuationFinancial support: This work was supported by AstraZeneca R&D Mölndal, Sweden. The sponsors played no part in the design or conduct of the study.
22 April 2013
Accepted after major revision: 07 August 2013
30 November 2017 (online)
It was the aim of this study to investigate whether low-dose acetylsalicylic acid (ASA) therapy for secondary cardiovascular prevention should continue, despite the risk of gastrointestinal bleeding. We aimed to make a clinically meaningful benefit–risk assessment regarding the cardiovascular and gastrointestinal consequences of ASA discontinuation. This case–control study used The Health Improvement Network UK primary care database to identify patients aged 50–84 years during 2000–2007 with a first ASA prescription for secondary cardiovascular prevention (N = 39,513). New cases of non-fatal myocardial infarction (MI)/coronary death (n = 1,222), ischaemic stroke (IS)/transient ischaemic attack (TIA) (n = 673) and upper gastrointestinal bleeding (UGIB) (n = 169) were identified after a mean follow-up of 3.2, 3.4 and 4.0 years, respectively. ASA discontinuers before the index date were identified. Attributable risks associated with ASA discontinuation were calculated and National Institute for Health and Clinical Excellence annual economic data were used to estimate healthcare costs. The cumulative incidences of non-fatal MI/coronary death, IS/TIA and UGIB among ASA discontinuers within the first year of follow-up were 17, 11 and 1.6 per 1,000 persons, respectively. This corresponds to eight extra cardiovascular events, and a reduction of 0.4 UGIB events per year compared with current ASA users. Extrapolating to the UK population aged over 50 years, avoiding discontinuation of ASA could prevent 12,786 coronary and 7,672 cerebrovascular events/year, at the expense of 1023 extra UGIB events, saving approximately £100 million/year. In conclusion, preventing patients with cardiovascular disease from discontinuing ASA could result in substantial clinical and economic gains.
KeywordsAspirin - medication adherence - Primary Health Care - cardiovascular - gastrointestinal haemorrhage
- 1 Martín-Merino E, Johansson S, Bueno H. et al. Discontinuation of low-dose acetylsalicylic acid therapy in UK primary care: incidence and predictors in patients with cardiovascular disease. Prag Obs Res 2012; 3: 1-9.
- 2 Herlitz J, Toth PP, Naesdal J. Low-dose aspirin therapy for cardiovascular prevention: quantification and consequences of poor compliance or discontinuation. Am J Cardiovasc Drugs 2010; 10: 125-141.
- 3 García Rodriguez LA, Cea-Soriano L, Martin-Merino E. et al. Discontinuation of low dose aspirin and risk of myocardial infarction: case–control study in UK primary care. Br Med J 2011; 343: d4094.
- 4 García Rodríguez LA, Cea Soriano L, Hill C. et al. Increased risk of stroke after discontinuation of acetylsalicylic acid: a UK primary care study. Neurology 2011; 76: 740-746.
- 5 Biondi-Zoccai GG, Lotrionte M, Agostoni P. et al. A systematic review and meta-analysis on the hazards of discontinuing or not adhering to aspirin among 50,279 patients at risk for coronary artery disease. Eur Heart J 2006; 27: 2667-2674.
- 6 Maulaz AB, Bezerra DC, Michel P. et al. Effect of discontinuing aspirin therapy on the risk of brain ischemic stroke. Arch Neurol 2005; 62: 1217-1220.
- 7 Sibon I, Orgogozo JM. Antiplatelet drug discontinuation is a risk factor for ischemic stroke. Neurology 2004; 62: 1187-1189.
- 8 Lotrionte M, Biondi-Zoccai GG. The hazards of discontinuing acetylsalicylic acid therapy in those at risk of coronary artery disease. Curr Opin Cardiol 2008; 23: 487-493.
- 9 Cea Soriano L, García Rodríguez LA. Risk of upper gastrointestinal bleeding in a cohort of new users of low-dose ASA for secondary prevention of cardiovascular outcomes. Front Pharmacol 2010; 1: 126-135.
- 10 O’Neil M, Payne C, Read J. Read Codes Version 3: a user led terminology. Methods Inf Med 1995; 34: 187-192.
- 11 Lewis JD, Schinnar R, Bilker WB. et al. Validation studies of the health improvement network (THIN) database for pharmacoepidemiology research. Pharmacoepidemiol Drug Saf 2007; 16: 393-401.
- 12 Pearce N. What does the odds ratio estimate in a case–control study?. Int J Epidemiol 1993; 22: 1189-1192.
- 13 Office for National Statistics. 2010 Population Estimates for UK, England and Wales, Scotland and Northern Ireland, mid 2009. http://www.ons.gov.uk/ons/publications/re-reference-tables.html?edition=tcm%3A77-213645 (16/07/2012).
- 14 Greenhalgh JB, Boland A, Martin Saborido A. et al. Clopidogrel and modified-release dipyridamole for the prevention of occlusive vascular events (review of Technology Appraisal No. 90): a systematic review and economic analysis. Health Technol Assess 2011; 15: 1366-5278.
- 15 Antiplatelet Trialists’ Collaboration. Collaborative overview of randomised trials of antiplatelet therapy—I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Br Med J 1994; 308: 81-106.
- 16 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: 71-86.
- 17 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: 1849-1860.
- 18 Björklund L, Wallander MA, Johansson S. et al. Aspirin in cardiology – benefits and risks. Int J Clin Pract 2009; 63: 468-477.
- 19 Patrono C, García Rodríguez LA, Landolfi R. et al. Low-dose aspirin for the prevention of atherothrombosis. N Engl J Med 2005; 353: 2373-2383.
- 20 Pratt S, Thompson VJ, Elkin EP. et al. The impact of upper gastrointestinal symptoms on nonadherence to, and discontinuation of, low-dose acetylsalicylic acid in patients with cardiovascular risk. Am J Cardiovasc Drugs 2010; 10: 281-288.
- 21 Moberg C, Naesdal J, Svedberg L-E. et al. Impact of gastrointestinal problems on adherence to low-dose acetylsalicylic acid: a quantitative study in patients with cardiovascular risk. Patient 2011; 4: 103-113.
- 22 Abraham NS, Hlatky MA, Antman EM. et al. ACCF/ACG/AHA 2010 expert consensus document on the concomitant use of proton pump inhibitors and thienopyridines: a focused update of the ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use. Circulation 2010; 122: 2619-2633.
- 23 Bhatt DL, Scheiman J, Abraham NS. et al. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. Circulation 2008; 118: 1894-1909.
- 24 van Haalen HGM, De Groot NL, Focks JJ. et al. All low dose aspirin users benefit from gastroprotection: results of a cost-utility analysis of competing strategies. Gut 2011; 60 (Suppl. 03) A158.
- 25 Saini SD, Fendrick AM, Scheiman JM. Cost-effectiveness analysis: cardiovascular benefits of proton pump inhibitor co-therapy in patients using aspirin for secondary prevention. Aliment Pharmacol Ther 2011; 34: 243-251.
- 26 Moukarbel GV, Bhatt DL. Antiplatelet therapy and proton pump inhibition: clinician update. Circulation 2012; 125: 375-380.
- 27 Martín-Merino E, Johansson S, Nagy P. et al. Effect of Baseline Gastrointestinal Risk and Use of Proton Pump Inhibitors on Frequency of Discontinuation of Aspirin for Secondary Cardiovascular Prevention in United Kingdom Primary Care. Am J Cardiol. 2013 doi: 10.1016/j.amjcard.2013.05.051. [Epub ahead of print].
- 28 Sud A, Kline-Rogers EM, Eagle KA. et al. Adherence to medications by patients after acute coronary syndromes. Ann Pharmacother 2005; 39: 1792-1797.
- 29 Burger W, Chemnitius JM, Kneissl GD. et al. Low-dose aspirin for secondary cardiovascular prevention - cardiovascular risks after its perioperative withdrawal versus bleeding risks with its continuation - review and meta-analysis. J Intern Med 2005; 257: 399-414.
- 30 Bedson J, Whitehurst T, Lewis M. et al. Factors affecting over-the-counter use of aspirin in the secondary prophylaxis of cardiovascular disease. Br J Gen Pract 2001; 51: 1001-1003.
- 31 Campbell NC, Thain J, Deans HG. et al. Secondary prevention in coronary heart disease: baseline survey of provision in general practice. Br Med J 1998; 316: 1430-1434.
- 32 Hopper S, Pierce M. Aspirin after myocardial infarction: the importance of over-the-counter use. Fam Pract 1998; 15 (Suppl. 01) S10-13.
- 33 Hansson L, Zanchetti A, Carruthers SG. et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet 1998; 351: 1755-1762.
- 34 de Gaetano G. Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Collaborative Group of the Primary Prevention Project. Lancet 2001; 357: 89-95.
- 35 Ridker PM, Cook NR, Lee IM. et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med 2005; 352: 1293-1304.
- 36 Medical Research Council’s General Practice Research Framework. 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. Lancet 1998; 351: 233-241.
- 37 He J, Whelton PK, Vu B. et al. Aspirin and risk of hemorrhagic stroke: a meta-analysis of randomized controlled trials. J Am Med Assoc 1998; 280: 1930-1935.
- 38 Rist PM, Buring JE, Kase CS. et al. Effect of low-dose aspirin on functional outcome from cerebral vascular events in women. Stroke 2013; 44: 432-436.