Has aspirin for primary prevention of CVD reached its expiration date?

- Kenny Lin, MD, MPH

A daily low-dose (81 mg) aspirin was once considered an essential component of cardiovascular disease (CVD) prevention for middle-aged and older adults. In 2006, the National Commission on Prevention Priorities ranked "discussing aspirin use in high-risk adults" the highest priority preventive service based on clinically preventable burden and cost effectiveness, and two years ago, in an updated set of rankings, it still rated aspirin use as the fifth highest priority for improving utilization. However, in 2018 the results of three large randomized trials suggested that the harms of aspirin taken to prevent a first CVD event outweigh its benefits for most persons. In an editorial in the June 1 issue of AFP, Dr. Jennifer Middleton and I reviewed the latest evidence and concluded:

The new data do not exclude the possibility that aspirin may still benefit adults at very high CVD risk (e.g., 20% or more over 10 years) or those at lower risk who are unable to tolerate statins, but the data otherwise suggest that the risks of low-dose aspirin therapy for primary prevention outweigh any potential benefits. For most patients, we should be deprescribing aspirin for primary prevention of CVD. To prevent heart attacks and strokes, family physicians should focus instead on smoking cessation and lifestyle changes, controlling high blood pressure, and prescribing statins when indicated.

In a 2019 clinical practice guideline, the American College of Cardiology / American Heart Association largely concurred, recommending against prescribing aspirin for primary prevention of CVD in adults older than age 70 and downgrading its role in other adults at high risk to "may be considered" on a case-by-case basis.

Although aspirin is still strongly recommended to prevent recurrent CVD events, its rise and fall in primary prevention seems to have become another case of medicine reversing itself. Unlike other notable examples of medical reversal such as menopausal hormone therapy and tight glucose control in type 2 diabetes, the effectiveness of aspirin was supported by many well-conducted randomized, controlled trials. Aspirin worked ... until it didn't. In a recent commentary in the Journal of General Internal Medicine, Palmer Greene and colleagues suggested that it may be a good idea to consider established evidence-based practices as having an "expiration date":

An “evidentiary statute of limitations” would require the occasional reassessment of accepted therapies to consider which might no longer be of use—possibly because of changes in the population as a whole, a changing understanding of whom the treatment is appropriate for, or evolving therapies for the prevention or treatment of the disease in question. Not only should we consider if older data still applies, we should also strive to anticipate the factors to which the results of a newly published positive study might be sensitive. For instance, is there an event rate in the control group below which the harms of the therapy might outweigh the benefit? Is there a treatment success rate that, when achieved, would make screening inefficient?

Not starting aspirin is relatively straightforward, but patients who have taken aspirin for many years without adverse effects or CVD events may resist discontinuing it. What approaches have you taken to this complex discussion?