Discontinuation of aspirin for secondary preventionBMJ 2011; 343 doi: https://doi.org/10.1136/bmj.d3942 (Published 19 July 2011) Cite this as: BMJ 2011;343:d3942
- 1Division of Cardiology, University of Modena and Reggio Emilia, 41124 Modena, Italy
- 2Department of Anaesthesia and Intensive Care, Università Vita-Salute San Raffaele, Milan, Italy
Is aspirin (acetylsalicylic acid) the wonder drug it is purported to be? It prevents atherothrombotic cardiovascular events, colorectal cancer, and venous thromboembolism and is cheap, effective, and safe.1 2 3 It has even been claimed that all elderly people should receive low dose aspirin plus other cardioprotective agents blended into a suitable polypill.4 The drawbacks are that the effects of aspirin vary greatly between individuals,5 and its role in the primary prevention of cardiovascular disease (in those without a clinical history of cardiovascular disease) has been challenged in several subsets of patients, including those with diabetes and peripheral artery disease.1
So what happens when aspirin is discontinued in patients with existing cardiovascular disease?6 In the linked case-control study (doi:10.1136/bmj.d4094), García Rodríguez and colleagues assess the effect of withdrawal of low dose (75-300 mg/day) aspirin in UK general practice when it has originally been prescribed for the secondary prevention of cardiovascular disease.7 Using a dataset of 39 513 patients followed for more than three years, the authors conducted a nested analysis of 1222 people who died as a result of coronary heart disease and 5000 random controls. They found that aspirin had been withdrawn in 12.2% of cases and 11.0% of controls. Compared with current use, recent discontinuation was associated with a clinically and statistically significant increase in the risk of non-fatal myocardial infarction (rate ratio 1.63, 95% confidence interval 1.23 to 2.14), and in the combined outcome of death from coronary heart disease and non-fatal myocardial infarction (1.43, 1.12 to 1.84). Conversely, the authors found no significant difference in the risk of death caused by coronary heart disease, but this might be because the statistical power was limited, as shown by the large confidence intervals. The most common reason for discontinuation was lack of adherence.
These findings are important and support previous studies showing an increase in adverse events after withdrawal of aspirin,6 8 9 although this is the first study to focus on general practice. Also, whereas most previous studies reported that thrombotic events occurred on average 11 days after discontinuation,6 García Rodríguez and colleagues defined recent aspirin discontinuation as at least 30 (or 15) days since discontinuation.7 Thus, any day off aspirin is a day at risk for patients with previous cardiovascular disease.
Does this evidence justify adding aspirin to tap water, as is the case with fluoride and has been suggested for statins?10 This could of course minimise the risk of aspirin discontinuation. However, García Rodríguez and colleagues’ results cannot be accepted uncritically. Firstly, the study was not a randomised trial of aspirin discontinuation (which would be justified in certain circumstances—for example, before major surgery). Secondly, we cannot tell if discontinuation of aspirin was appropriate on personal or clinical grounds, because statistical adjustment was possible only for known confounders. Thirdly, the thrombotic and ischaemic events that might be prevented by more rigorous compliance with aspirin therapy may be offset, at least in selected settings, by an increase in bleeding risk. The risk-benefit ratio of aspirin in individual patients should always be considered,11 and this is even more important in relation to primary prevention, because the ratio is much less favourable in the absence of a clinical history of cardiovascular disease.11
Time, as usual, will tell, with the help of trials such as the upcoming PeriOperative Ischemic Evaluation-2 (POISE-2) study, which is randomising 10 000 patients undergoing non-cardiac surgery to aspirin or clonidine (or both) versus placebo, and the Aspirin and Tranexamic Acid for Coronary Artery Surgery (ATACAS) study, which is randomising 4600 patients undergoing coronary artery bypass grafting to aspirin or tranexamic acid (or both) versus placebo. Further similar studies are eagerly awaited in relation to outpatient procedures and people with continuous but non-severe bleeding.
In the meantime, patients on chronic low dose aspirin for secondary prevention of cardiovascular disease should be advised that unless severe bleeding ensues or an informed colleague explicitly says so, aspirin should never be discontinued given its overwhelming benefits on atherothrombosis, as well as colorectal cancer and venous thromboembolism.1 2 3 Accordingly, doctors should maintain their patients on low dose aspirin as long as they can and carefully assess individual patients for the risk of both thrombosis and bleeding before discontinuing aspirin for invasive procedures.12 Patients who need to discontinue aspirin should do so for the minimum time necessary.
Cite this as: BMJ 2011;343:d3942
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Provenance and peer review: Commissioned; not externally peer reviewed.