Is aspirin good primary prevention for heart disease?

By Naveed Saleh, MD, MS, for MDLinx
Published November 9, 2018

Key Takeaways

Scientists had synthesized aspirin by the beginning of the 20th century, but only now are researchers beginning to understand its role in the primary prevention of heart disease—a role that may turn out to be very small, studies suggest.

“For secondary prevention, in which risk is determined largely by the extent of atherosclerotic disease, the benefits of aspirin outweigh the risks of bleeding,” according to a New England Journal of Medicine editorial written by Paul M. Ridker, MD, director, Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, Boston, MA. “In contrast, for primary prevention, in which risk is determined largely by age and the presence or absence of diabetes, the benefit–risk ratio for prophylactic aspirin in current practice is exceptionally small.”

A recent trifecta of results from aspirin primary-prevention trials have given physicians new data to ponder when prescribing aspirin: 1) the ASCEND (A Study of Cardiovascular Events in Diabetes) trial examined participants with diabetes; 2) the ARRIVE (Aspirin to Reduce Risk of Initial Vascular Events) trial examined aspirin use in moderate-risk participants without diabetes; and 3) the ASPREE (Aspirin in Reducing Events in the Elderly) trial involved older participants who were relatively healthy. All of these studies aimed to determine the use of aspirin for primary prevention of cardiovascular events.

• ASCEND. The ASCEND trial involved 15,480 participants with diabetes who were randomized to receive either 100 mg of aspirin daily vs. placebo. During an average follow-up of 7.4 years, the rate of serious vascular events was 8.5% vs. 9.6% with placebo. Furthermore, aspirin use was linked to a 12% drop in the rate of serious vascular events, but a 29% increase in the rate of major bleeding events. All-cause mortality was no different among groups.

• ARRIVE. Investigators in the ARRIVE trial examined the primary preventive effects of aspirin at 100 mg daily vs. placebo in 12,546 patients without diabetes but with moderate risk of cardiovascular disease. On the basis of the intention-to-treat analysis, the team found that the incidence of the composite primary outcome of myocardial infarction, stroke, unstable angina, transient ischemic attack, or death from cardiovascular causes was 4.3% with aspirin vs 4.5% with placebo. Furthermore, the incidence of gastrointestinal bleeding events with aspirin was double that of placebo. Finally, there was no difference between all-cause mortality and fatal bleeding events between both groups.

• ASPREE. Researchers in the ASPREE trial examined the preventive effects of 100 mg of aspirin daily vs. placebo in 19,114 Australian and US patients aged 70 years and older without initial cardiovascular disease, dementia, or disability. As with the ARRIVE trial results, the team found no evidence of cardiovascular benefit from aspirin, but patients taking aspirin had higher major bleeding risk.

The ASPREE investigators found that the rate of death from any cause was possibly heightened in those taking aspirin, which conflicts with results of the ARRIVE, ASCEND, and similar trials. Intriguingly, this increased mortality was observed only in the Australian cohort and was fueled by a surprisingly higher risk for cancer-related death with aspirin (hazard ratio 1.31; 95% CI 1.10 to 1.56).

Results indicating increased cancer risk in the ASPREE study should be taken with a grain of salt, noted ASPREE researchers.

“The biologic basis for either an early or a delayed effect of aspirin on cancer is unclear,” wrote researchers led by John J. McNeil, MBBS, PhD, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia. “Other primary prevention trials of aspirin have not identified similar results, which suggests that the mortality results reported here should be interpreted with caution.”

Finally, Dr. Ridker suggested that based on previous research, statins may be a better primary preventive strategy than aspirin. In primary prevention trials, statin use was correlated with a 25% lower risk for major vascular events for every 1 mmol per liter reduction in low-density lipoprotein levels.

“Beyond diet maintenance, exercise, and smoking cessation, the best strategy for the use of aspirin in the primary prevention of cardiovascular disease may simply be to prescribe a statin instead,” Dr. Ridker concluded.

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