A Guide to Deprescribing Aspirin
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A GUIDE TO deprescribing ASPIRIN KEY POINTS CONTEXT This guide considers the use of aspirin for prevention of vascular events. U Aspirin treatment is effective in preventing recurrence RECOMMENDED of cardiovascular events in DEPRESCRIBING STRATEGY those patients with previous cardiovascular events. The U Patients with a high risk of gastrointestinal bleeding (e.g. elderly, absolute risk reduction for taking other GI bleed inducing agents such as NSAIDs, SSRIs and secondary prevention is 2-4% corticosteroids, alcohol users, smokers) should be considered for per year (NNT 25-50). This risk cessation of antiplatelet agents. reduction may be lower in people U Patients with a low cardiovascular risk should be considered for whose event was greater than 5 cessation of antiplatelet agents. years previously. U Patients receiving dual antiplatelet agents should generally have one of these ceased within 12 months of the acute event. For patients where U For primary prevention, the bleeding risk is higher, earlier cessation may be appropriate. absolute risk reduction for aspirin U Patients with troublesome adverse effects associated with antiplatelet is significantly lower and is highly agents should be reassessed for the ongoing risk vs benefit of the dependent on the underlying antiplatelet agent. absolute risk. In patients with U Patients with a limited prognosis should be considered for cessation of one or two risk factors for antiplatelet agents. cardiovascular disease, the U Antiplatelet agents can usually be stopped without the need for absolute risk reduction is of the tapering. order of 0.2-0.4% (NNT 250-500 per year). In healthier patients, BENEFIT VERSUS HARM the number needed to treat for aspirin primary prevention approaches 2000 for one year. Favours Favours U Continuing Deprescribing Older patients have a Medication Medication significantly higher risk of major bleeding, with people over Decreased Benefits 85yo having up to a 7% annual [ Low cardiovascular risk (no established CVD) bleeding risk. Main Benefits Increased Benefit [ Limited life expectancy [ [ due to comorbidities U The risk of gastrointestinal Reduced High cardiovascular vascular events risk (usually secondary (dementia, heart failure, and other extracranial bleeding prevention) airways disease, malignancy) is also increased by other patient factors (e.g. previous GI bleeding/ Increased Harms ulceration history, severe [ Concurrent use of other renal dysfunction, concurrent gastrointestinal irritantsPAGE 1 (e.g. NSAIDs, SSRIs, medications, smoking and corticosteroids) alcohol use). Main Harms Reduced Harms [ Co-prescription of a [ Gastrointestinal [ Concurrent use of PPIs second antiplatelet or U Recurrent minor bleeding can and other or other gastric acid anticoagulant [ bleeding suppression Advanced age have a significant impact on [ Prior gastrointestinal patients’ quality of life. pathology (e.g. prior gastric ulcer, erosions) FOR BETTER HEALTH OUTCOMES PAGE 1 ASPIRIN EFFICACY SECONDARY PREVENTION PRIMARY PREVENTION Low-dose aspirin has been shown to be effective in preventing about one-fifth For primary prevention, the balance of atherothrombotic vascular complications (non-fatal myocardial infarction, between vascular events avoided non-fatal stroke, or vascular death) in patients with previous myocardial and major bleeds caused by aspirin is 1,2,3,4 infarction, stroke, or transient cerebral ischaemia. substantially uncertain because the risks This corresponds to an absolute reduction of about 10–20 per 1000 patients without aspirin, and hence the absolute in the yearly incidence of non-fatal events, and to a smaller, but still definite, benefits of antiplatelet prophylaxis, are at reduction in vascular death. approximately an order of magnitude lower In 1994, the Antiplatelet Trialists’ Collaboration,5 concluded that owing to the than in secondary prevention (less than 4 vs higher baseline risk, the absolute benefit is greater in older than in younger 38 per 1000 patients benefit). patients. In patients below 65 years of age, 11% of patients taking aspirin had There are ten available trials examining vascular events compared to the baseline risk of 14.3% for patients taking the use of aspirin for primary prevention. placebo (ARR 3.3%, NNT= 30). For patients over 65 years of age, the baseline The key significant results are summarised event rate was 23.2% and this was compared to the aspirin event rate of 18.7% below: (ARR 4.5%, NNT= 22). U Physicians Health Study6: 34% reduction In 2002, the Antithrombotic Trialists’ Collaboration analysed 16 trials of long-term in MI (ARR 0.185% pa, NNT=540) aspirin use with doses ranging from 50–150 mg/day for secondary prevention of 7 CVD events, including over 17,000 subjects and 3,306 serious vascular events.4 U Thrombosis Prevention Trial : 20% In these trials, aspirin use resulted in significant reductions in serious vascular reduction in MI (ARR 0.23% pa, NNT= 435) events including stroke and coronary events in both men and women and low U Hypertension Optimal Treatment8: 15% dose regimens (75–100 mg/day) were found to be as effective as higher doses. reduction in any cardiovascular event (ARR 0.16% pa, NNT= 625); 36% reduction Aspirin use as a secondary prevention measure for serious CVD events is in MI (ARR 0.13% pa, NNT=769) well accepted and recommended by several major organizations. U Primary Prevention Project9: 23% reduction in any cardiovascular event 60 NNT (Annualised ARR 0.475%, NNT 211) and 44% reduction in cardiovascular mortality (Annualised ARR 0.15%, NNT= 667) 50 Unstable angina 20 U Womens Health Study10: 17% reduction in stroke (ARR 0.255%, NNT=392) 11 40 U British Doctors Trial ,Prevention Of Progression of Arterial Disease And Diabetes12, Aspirin for Asymptomatic 30 Atherosclerosis13, Japanese Primary prevention with Aspirin for Diabetes14, ASPirin for the Reduction of Events in 20 Survivors of MI 55 the Elderly15,16,17 No significant benefit aspirin per 1000 treated for 1 year for per 1000 treated aspirin 100 Trial results were mixed to some degree, but Stable angina 10 the preponderance of evidence suggested Subjects in whom a vascular event is prevented by by is prevented event Subjects in whom a vascular that aspirin decreases relative CVD risk, 1667 Healthy subjects 0 including MI and stroke by 6-30% (absolute 0 5 10 15 20 benefit varies from zero to 0.47% per year, Annual risk of a vascular event with placebo (%) NNT=220 or more). Figure 1: Absolute benefit of aspirin for patients with different cardiovascular risk20 A number of meta-analyses of these trials have been undertaken. 4,18,19 Overall, aspirin DUAL ANTIPLATELET THERAPY allocation yielded a 12% proportional (ASPIRIN WITH CLOPIDOGREL, TICAGRELOR OR PRASUGREL) reduction in major vascular events, due Dual antiplatelet therapy is now recommended by the American Heart mainly to a reduction by about one-fifth Association (AHA) guidelines for use after acute cardiac syndromes (unstable in non-fatal myocardial infarction. This angina, myocardial infarction, coronary artery procedures) for 12 months, proportional benefit would translate into unless there are significant contraindications, in which case aspirin alone is a number-needed-to-treat (NNT) of ~2000 recommended.21 In cerebrovascular disease, dual antiplatelet therapy may low-risk individuals to prevent one non-fatal also be useful for up to 3 months after acute stroke or TIA.22 The reduction myocardial infarction. in cerebrovascular events occurred primarily in the first 30 days of dual Absolute benefit of aspirin therapy can antiplatelet treatment, while the bleeding complications occurred in the therefore be related directly to absolute second and third months. risk of a cardiovascular complication. The Patients age 75 and older have been underrepresented in clinical trials of acute number needed to treat to prevent a coronary syndrome and specific guidance for duration of dual antiplatelet vascular event increases from 20 in patients therapy is unclear. Indeed, the AHA guidelines state ”Management decisions with stable angina to 1667 in healthy for older patients with NSTE-ACS should be patient centered, and consider subjects (see Figure 1).20 patient preferences/goals, comorbidities, functional and cognitive status, and life expectancy.” 21 deprescribing FOR BETTER HEALTH OUTCOMES PAGE 2 ASPIRIN ADVERSE EFFECTS The balance between preventing vascular NNH=17 occlusion and causing excess bleeding with aspirin 120 No history, control No history, aspirin depends critically on the absolute thrombotic 105 Gastrointestinal pain, control Gastrointestinal pain, aspirin (see Figure 2) vs. haemorrhagic risk of the patient (Figure 3). In elderly patients with a history of a Uncomplicated ulcer, control Uncomplicated ulcer, aspirin 90 gastrointestinal ulcer, taking aspirin, the NNH is Complicated ulcer, control Complicated ulcer, aspirin estimated as 17, while in younger patients with no 75 prior GI history, the NNH is 1667. While patients at relatively low cardiovascular risk may not have 60 a net clinical benefit, in patients at high risk of cardiovascular or cerebrovascular complications 45 (e.g. patients with unstable angina or prior 30 myocardial infarction), the absolute benefit of aspirin prophylaxis will likely outweigh the 15 published rate of harm of a 1-2/1000 rate of GI NNH=1667 23,24 bleeding per year. complications/1000 person–year of upper gastrointestinal Rate 0 The published rate is, however, based on clinical <50 50–59 60–69 70–79 ≥80 trial participants, and