HOT OFF THE PRESS!

Debra L. Beck and Eugene Braunwald, MD

Date Published: August 16, 2019

Three new trials published in the past year have pushed the debate on the efficacy and safety of aspirin for primary prevention of cardiovascular disease (CVD) back to the forefront. Abdelaziz et al conducted an updated meta-analysis of recent large trials, including >45,000 individuals from the three new trials, to provide comprehensive and updated information on the efficacy and safety of aspirin for primary prevention of CVD.

A total of 15 controlled trials (with at least one year of follow-up) including 165,502 participants (mean age, 61.5 years) were included. All compared aspirin (any dose) to controls (placebo or no aspirin).

Aspirin was associated with similar all-cause death (relative risk [RR], 0.97; p=0.64), cardiovascular (CV) death (RR: 0.93; p=0.88), and non-CV death (RR: 0.98; p=0.53), compared to control. Aspirin did, however, lower the risk of total myocardial infarction (MI) (RR, 0.85; p=0.001), nonfatal MI (RR: 0.82; p=0.004), and ischemic stroke (RR, 0.87; p=0.002), albeit accompanied by a trend towards an increase in hemorrhagic stroke (RR, 1.21; p=0.059). Fatal MI was not significantly decreased with aspirin compared to control (RR, 0.93; p=0.31).

A composite of nonfatal MI, nonfatal stroke, transient ischemic attack or CV death utilizing data from 6 controlled trials showed a benefit for aspirin (RR, 0.903; p=0.001).

Major bleeding was more common with aspirin (RR, 1.5; p<0.001), as was intracranial bleeding including hemorrhagic stroke (RR: 1.32; p=0.001), and major GI bleeding (RR: 1.52; p<0.001). Fatal bleeding did not differ significantly with aspirin compared to controls (RR: 1.09; p=0.6). A dose-related increased in bleeding was noted.

At a mean follow-up of 6.46 years, total cancer incidence (RR, 0.99; p=0.85) and cancer-related death (RR, 0.90; p=0.92) were similar in those treated with aspirin compared to controls.

Summary

The investigators concluded that aspirin for primary prevention reduces nonfatal ischemic events (but not death, CV death, or fatal MI) and significantly increases nonfatal bleeding events. The authors noted that most of the studies included had composite endpoint, which they separated into individual endpoints to overcome the issue of heterogeneity in the definition of composite outcomes. This, along with the lack of individual patient data, limit their findings.

Comment

Despite the large number of high-quality trials included in this meta-analysis, the data on aspirin for primary prevention remains lacking, said editorialist Dr. M Pignone. Specifically, more information is needed on the impact of aspirin on all-cause mortality and cancer incidence, along with better information on women, people with diabetes, and those using other cardiovascular risk-reducing medications, particularly statin drugs. Until then, modeling studies that consider not just the number of events prevented and bleeds caused, but also the health effects of events, indicate that aspirin for primary prevention should be reserved for those with the greatest potential net benefit—adults with increased CV risk but not at increased risk of bleeding.

References

• 1. HK Abdelaziz, M Saad, NVK Pothineni, et al: Aspirin for Primary Prevention of Cardiovascular Events. J Am Coll Cardiol. 73(23): 2915-2929. 2019 Jun 18. 31196447
• 2. M Pignone: What Is So Hard About Aspirin for Primary Prevention? J Am Coll Cardiol. 73(23): 2930-2931. 2019 Jun 18. 31196448

Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine features a unique update program by Dr. Braunwald, creating a “living textbook” by featuring weekly Hot off the Press, periodic Late-Breaking Clinical Trials (including links to authors’ presentation slides), and monthly Focused Reviews.

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