"It's Not You, It's Me" - Is it Time to Break Up With Aspirin?

Michael D. Miedema, MD; Thomas Knickelbine, MD, FACC


July 25, 2019

The recently released 2019 American College of Cardiology/American Heart Association Guideline on the Primary prevention of Cardiovascular Disease includes recommendations on the use of aspirin for primary prevention of CVD.[6] Based largely on the results of the three recent trials, the committee gave a class III: Harm recommendation for use of aspirin for primary prevention in patients ≥70 years old as well as in individuals at increased risk of bleeding such as those on oral anticoagulants or a history of a prior bleeding episode. For adults age 40-70 years old, the guidelines give a class IIb recommendation that aspirin may be considered for primary prevention in those who are at higher CVD risk and not at increased bleeding risk.

Reconciling the declining benefit of aspirin for primary prevention can likely be largely explained by three key factors. First, decreases in population rates of CVD, especially myocardial infarction,[7] have contributed to limiting the benefit of aspirin in recent trials. With improved control of blood pressure and cholesterol and lower rates of smoking in modern populations, it is difficult to identify high-risk primary prevention patients. In ARRIVE, despite the sample having multiple risk factors and an estimated 10-year risk of ~17%, the event rates were more consistent with a low risk population, leaving little room for aspirin to achieve a significant benefit.[5] Second, a change in reported outcomes has likely contributed the decline in benefit. The main reported outcome for the aspirin component of the Physician's Health Study was myocardial infarction, which was reduced by 44%.[8] The recent trials have primary outcomes that are composites of total CVD, including CVD death. There are multiple different mechanisms that could lead to CVD death that are not atherothrombotic in etiology (heart failure, dissection, arrhythmia, etc.) and therefore unlikely to be affected by aspirin. Finally, with studies that require long duration of follow-up, an intention to treat analysis does come with a risk of bias towards a null result. In ARRIVE, in the intention to treat analysis there was no significant reduction in myocardial infarction (HR 0.85 [95% CI 0.64-1.11]). However, approximately 30% of ARRIVE participants terminated the study prematurely. In the per-protocol analysis, including only those who remained on their assigned treatment for the duration of the study, there was a 47% reduction in myocardial infarction (p-value 0.0014) with use of aspirin.[5]

In summary, the three recent trials have confirmed the notion that the benefit of aspirin in modern primary prevention populations is small and for most individuals is probably not worth the risk in bleeding. However, for individuals who are at elevated CVD risk and low risk of bleeding, consideration for use of aspirin is reasonable and should be discussed in the context of shared decision making between the patient and their provider. Should we break up with aspirin for primary prevention? For many of us, the answer is yes, but we should understand that it isn't aspirin that's changed, we have.