Aspirin for primary cardiovascular disease prevention: time to re‐evaluate guidelines?

Abstract

The recommendations for aspirin use in the primary prevention of cardiovascular disease (CVD) in Australians at elevated risk have changed over time as the body of literature informing them grows. Current practice is largely against prescribing primary preventative aspirin; however, the recent review of the American Diabetes Association (ADA) cardiovascular standards of medical care in diabetes suggests it is time this was reviewed. The issue is complicated by multiple studies with inconsistent findings across risk groups. Of the 11 published randomised control trials of aspirin for CVD primary prevention in high-risk individuals, the current Australian cardiovascular risk modification guidelines published in 2012 by the National Vascular Disease Prevention Alliance considered results from 9. They state that ‘Aspirin or other antiplatelet therapy is not routinely recommended for primary prevention of CVD’ (a Grade B recommendation) including for high-risk patients, defined as a ‘>15% absolute risk of CVD events over 5 years’. The Hypertension Optimal Treatment (HOT) trial (1998) is the only one of the 11 referred to above that achieved its primary outcome of a reduction in three-point major adverse cardiovascular events. However, six of the trials showed a statistically significant reduction in non-fatal myocardial infarction (MI). A 2016 meta-analysis including all of these trials showed an overall relative risk (RR) of 0.78 (95% confidence interval (CI) 0.71–0.87, P = 0.005) for aspirin use versus placebo for non-fatal MI. Subgroup analysis by risk level found that aspirin use in patients at an 8.44% absolute risk of CVD events over 10 years (the highest risk group considered) prevented 1.43 events per 1000 patientyears, or a number needed to treat of 70 over 10 years. Analysis of the same data found that aspirin caused 1.39 major bleeding events (resulting in death, hospitalisation, transfusion or described as serious by investigators) per 1000 patient-years, or a number needed to harm of 72 over 10 years. On the strength of these data the ADA recommends ‘Aspirin therapy... may be considered as a primary preventative strategy in those with type 1 or type 2 diabetes who are at increased cardiovascular risk’ (a Grade C recommendation). The United States Preventative Services Taskforce goes further and recommends that clinicians should ‘initiate low-dose aspirin’ (a Grade B recommendation) in adults 50–59 years with a ≥10% 10-year CVD risk; this can be considered in the 60–69 age group (a Grade C recommendation). Aspirin increases both non-fatal and fatal bleeding and this must be considered in any patient before commencing. However, we may be missing an opportunity to prevent many non-fatal MI, an important cause of morbidity in a high-risk population, with a cheap and acceptable intervention. It is time our guidelines were reviewed. Since the submission of this letter for publication three modern trials of primary preventative aspirin have been published. Aspirin was associated with no cardiovascular benefit in the elderly, but low-risk (3.45–3.88% 5-year event-rate) ASPirin in Reducing Events in the Elderly (ASPREE) population (hazard ratio (HR) 0.95, 95% CI 0.83–1.08, P > 0.05) or the low-to-moderate-risk (4.29–4.48% 5-year event-rate) Aspirin to Reduce Risk of Initial Vascular Events (ARRIVE) trial (HR 0.96, 95% CI 0.81–1.13, P = 0.604). The high-risk (8.5–9.6% 7.4-year event-rate) A Study of Cardiovascular Events iN Diabetes (ASCEND) trial did show a benefit (RR 0.88, 95% CI 0.79–0.97, P = 0.01), but at the cost of increased major bleeding (RR 1.29, 95% CI 1.09–1.52, P = 0.003). This large modern dataset studied in the context of Letters to the Editor