The use of aspirin as a primary prevention for atherosclerotic cardiovascular disease (ASCVD) in high-risk patients has been controversial. Aspirin is known to lower the risk of heart attack and stroke, but it also may increase the risk of major bleeding episodes. In a new study, researchers have found no evidence that the use of aspirin for higher-risk primary prevention is beneficial. The study was published in The American Journal of Medicine.

The study authors used a database to examine all prospective randomized clinical trials (RCTs) that tested aspirin as a primary prevention method for ASCVD and evaluated at least 1 of the following primary endpoints: fatal and nonfatal myocardial infraction, fatal and nonfatal ischemic stroke, and major bleeding, which was self-defined by each RCT individually.

Researchers also conducted an exploratory analysis to observe how the year of study publication impacted aspirin’s treatment effect for primary ASCVD prevention. In a subgroup analysis, studies were separated based on whether they were published prior to 2010, or during or after 2010. Researchers created additional subgroups for patients who were treated with higher doses of aspirin (>100 mg/d) and lower doses of aspirin (≤ 100 mg/day) to analyze bleeding risk.

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A total of 12 RCTs that compared aspirin with nonaspirin (either placebo or control) for primary ASCVD prevention were identified (n=145,435); these RCTs included a total of 963,829 patient-years of follow-up. The included studies were published from 1988 to 2018, and the dose of aspirin ranged from 75 mg to 500 mg per day. The mean age of participants was 62.7 years, and the mean duration of follow-up was 6.8 years.

Patients treated with aspirin had a statistically significant reduction in ASCVD events compared with no aspirin (4.7 vs 5.3 events per 1000 patient-years). Despite the beneficial effects, the authors found a statistically significant increase in major bleeding events for patients treated with aspirin compared with control patients (2.5 vs 1.8 events per 1000 patient-years). “These results trended toward an increased benefit for aspirin in higher-risk patients, but this finding did not meet statistical significance,” the researchers reported.

In studies published prior to 2010 (n=7) and during or after 2018 (n=5), aspirin use resulted in a statistically significant reduction of ASCVD events. Researchers found that aspirin had a greater treatment effect in older trials compared with newer trials. The study authors found no heterogeneity of treatment effect between higher vs lower doses of aspirin and major bleeding events.

“While there was a statistically significant reduction in ASCVD events among individuals randomized to aspirin, this is unlikely to be clinically significant when bleeding risk is taken into consideration,” the researchers said. “Furthermore, this reduction in ASCVD events is less than other treatment modalities aimed at primary prevention… despite the thought that aspirin for primary prevention may still be useful for those at high risk for ASCVD, insufficient randomized data currently exist to recommend aspirin in this group,” concluded the authors.


Nudy M, Cooper J, Ghahramani M, Ruzieh M, Mandrola J, Foy A. Aspirin for primary atherosclerotic cardiovascular disease prevention as baseline risk increases: a meta-regression analysis. Am J Med. Published online May 20, 2020. DOI: 10.1016/j.amjmed.2020.04.028