Is aspirin effective primary prevention for CVD?

- Jennifer Middleton, MD, MPH

Two recent studies challenge the premise that adults at increased risk of cardiovascular disease (CVD) should take a daily aspirin. More specifically, the United States Preventive Services Task Force (USPSTF) currently recommends that adults aged 50-59 with a 10-year risk of CVD of at least 10% take a daily low-dose aspirin. One of the studies published earlier this week, however, found no benefit to daily aspirin use regarding primary prevention of CVD but did find an increased risk of gastrointestinal (GI) bleeding; the other study found that aspirin did decrease the risk of initial CVD events in its participants with diabetes but it also, again, increased the risk of GI bleeding.

The first study, the ARRIVE study, enrolled over 12,000 participants across several countries (most participants came from the United Kingdom, Germany, and Poland) deemed to be at "moderate" risk of CVD based on a lengthy list of criteria that resulted in a mean ASCVD risk score for participants of approximately 17%. Participants were randomized into either the aspirin (100 mg of enteric-coated aspirin a day) group or the placebo group and were followed for an average of 5 years. The researchers' primary outcome was a composite of first occurrence of cardiovascular death, myocardial infarction, unstable angina, stroke, or transient ischemic attack. There was no difference in the rate of these events between the aspirin and the placebo groups (hazard ratio 0.96; 95% confidence interval [0.81-1.13]), but the aspirin group had a higher rate of GI bleeding events (hazard ratio 2.11; 95% confidence interval [1.36-3.28]).

Interestingly, though the mean ASCVD risk score for enrolled participants was 17.3-17.4%, the rate of CVD events that actually occurred among participants was much lower; only 4.29-4.48% of participants had a CVD event during this study. The researchers attribute this difference to good management of non-acute CVD symptoms and note this trial was intentionally "pragmatic" in this regard, though they do also concede that "risk calculators developed with older data might overestimate risk in current practice." Concerns about the ASCVD risk score's propensity to inflate CVD risk are not new and have even been acknowledged within the cardiology community. Unfortunately, as the USPSTF notes in their statement, "although concerns have been raised about the equations’ potential to overpredict risk and their moderate discrimination, they are the only U.S.-based, externally validated equations that report risk as a combination of cerebrovascular and CHD events."

The second study, the ASCEND study, enrolled over 15,000 participants across the United Kingdom with diabetes but without known CVD and randomized them into daily aspirin (100 mg of aspirin a day) or placebo groups. Participants were followed for an average of 7.4 years. Unlike the ARRIVE study, the ASCEND researchers found that CVD events were decreased in the aspirin group (relative risk 0.88; 95% confidence interval [0.79-0.97]), but, similar to ARRIVE, GI events were increased in the aspirin group (relative risk 1.29; 95% confidence interval [1.09-1.52]). The researchers concluded that "[t]he absolute benefits were largely counterbalanced by the bleeding hazard." Additionally, "91 patients would need to be treated to avoid a serious vascular event over a period of 7.4 years, and 112 to cause a major bleeding event."

Both of these studies looked at relatively high risk populations for CVD and had a large number of participants. The ARRIVE study's participants did not have diabetes, while the ASCEND study's participants did. Both groups of researchers, however, came to the same conclusion: the risks of taking daily aspirin for primary prevention of CVD outweigh any possible benefit.

Dr. Lin and I have both previously written about aspirin as primary prevention on the blog, and you can count on AFP to continue bringing you the latest evidence to inform your practice. Will these new studies change your recommendations about aspirin for primary prevention of CVD?