Does an Aspirin a Day Keep the Doctor Away?

Digging into the research on this changing topic



Increasingly, it seems, the short answer to this question is "no."

Decades-old research, such as the Physicians' Health Study and the Women's Health Study, had demonstrated that, for middle-age adults, aspirin modestly reduces cardiovascular events, but also increases bleeding risk. Older studies have also suggested modest benefits of aspirin with respect to preventing colorectal cancer.

Based on this prior research, the current U.S. Preventive Services Task Force (USPTF) guideline provides the somewhat nebulous recommendation that, for adults ages 50-59 years, aspirin should be initiated for primary prevention of cardiovascular disease and prevention of colorectal cancer risk among those with a 10-year cardiovascular disease risk of ≥10% who are not at increased bleeding risk and have a ≥10 year life expectancy as well as willing to take aspirin daily for 10 years. For adults ages 60-69 years, the USPSTF recommends that initiation of low-dose aspirin should be individualized (as if that is a distinction from the recommendation for patients ages 50-59 years!).

Recently, however, new research has emerged that offers new insights on the pros and cons of daily aspirin use. Last October, the New England Journal of Medicine reported four trials evaluating aspirin for primary prevention of cardiovascular disease. Three of the new trials failed to demonstrate a benefit of ASA for primary cardiovascular prevention or disability-free survival among older adults, and suggest some harms, including increased bleeding risk and a possible increase in all-cause mortality. The fourth trial showed that among patients with diabetes, aspirin use modestly lowered cardiovascular risk but caused higher rates of bleeding, which "largely counterbalanced" the benefits.

This January, a new meta-analysis published in JAMA summarized findings from all 13 randomized trials (including the 2018 NEJM studies) with at least 1,000 participants and a follow-up of at least 12 months examining the impact of daily aspirin for primary cardiovascular prevention. The new analysis concluded that aspirin in this population "was associated with a lower risk of cardiovascular events [number needed to treat, 265] and an increased risk of major bleeding [number needed to harm, 210]."

An accompanying editorial explains that "the similarity of the number needed to treat (265) and the number needed to harm (210) has been the rationale for some guidelines that recommend not using aspirin for primary prevention." However, the USPTF guidelines call for a shared decision-making process with patients involving a careful discussion of "patient preferences regarding vascular and bleeding events," and colorectal cancer risk.

In another excellent editorial in NEJM on the new findings, Paul Ridker -- the lead author of the Women's Health Study from two decades ago -- argues that in the modern era in which statin use for patients with cardiovascular risk factors is widespread and smoking rates are on the decline, "the benefit-risk ratio for prophylactic aspirin in current practice is exceptionally small." In Ridker's view, rather than focusing our attention on aspirin use for primary cardiovascular prevention, our efforts would be better spent identifying which of our patients might benefit from statins -- which may have a more favorable overall benefit-to-risk profile.

Overall, we agree with Ridker. Our Slow Medicine approach to aspirin has been a cautious one, only recommending it for middle-age patients with multiple cardiovascular risk factors, low bleeding risk, and who are keen on using it. Our list of patients in this category is quite small.

With respect to Ridker's final point about considering statins for primary cardiovascular prevention, we agree that the evidence for statins is more robust than for aspirin. Still, we remain cautious about statins because these medications also have harms (e.g., myopathy, diabetes, and potentially even herpes zoster) that adversely impact quality of life. Again, we advocate for statin use for primary prevention only for our patients at elevated cardiovascular risk who are open to using a preventative medication and who do not suffer substantial side effects after initiating treatment.

We hope, someday, there will be better treatments with fewer side effects for the primary prevention of cardiovascular disease. Until that day comes, we will continue to emphasize blood pressure control and lifestyle changes -- especially smoking cessation, exercise, and a healthy diet -- as the safest, most effective strategy to lower cardiovascular risk, with medications like aspirin and statins reserved for high-risk individuals who opt to take them after carefully considering the pros and cons.

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