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Aspirin for the Primary Prevention of Cardiovascular Disease: Weighing Up the Evidence

Author/s: 
Murphy, Sean, McCarthy, Cian P., McEvoy, John W.

Aspirin is one of the most universally recognized and commonly prescribed medications worldwide. It is estimated that 48.7 million U.S. adults are taking aspirin for cardiovascular disease prevention; the majority (~73%) for primary prevention. The benefit of aspirin for secondary prevention of cardiovascular disease is well-established, with meta-analysis results favoring low dose (75–150 mg/day) over high dose (>150 mg/day) aspirin given similar efficacy but lower bleeding risk. In contrast, the role of aspirin in primary cardiovascular disease prevention is more controversial; historical trials found benefit but trials since 2008 have shown either null effects on all-cause and cardiovascular disease mortality or a signal for increased mortality in the context of excess bleeding.

Keywords 
aspirin cardiovascular events

Association of Aspirin Use for Primary Prevention With Cardiovascular Events and Bleeding Events: A Systematic Review and Meta-analysis

Author/s: 
Zheng, Sean L., Roddick, Alistair J.

IMPORTANCE:

The role for aspirin in cardiovascular primary prevention remains controversial, with potential benefits limited by an increased bleeding risk.

OBJECTIVE:

To assess the association of aspirin use for primary prevention with cardiovascular events and bleeding.

DATA SOURCES:

PubMed and Embase were searched on Cochrane Library Central Register of Controlled Trials from the earliest available date through November 1, 2018.

STUDY SELECTION:

Randomized clinical trials enrolling at least 1000 participants with no known cardiovascular disease and a follow-up of at least 12 months were included. Included studies compared aspirin use with no aspirin (placebo or no treatment).

DATA EXTRACTION AND SYNTHESIS:

Data were screened and extracted independently by both investigators. Bayesian and frequentist meta-analyses were performed.

MAIN OUTCOMES AND MEASURES:

The primary cardiovascular outcome was a composite of cardiovascular mortality, nonfatal myocardial infarction, and nonfatal stroke. The primary bleeding outcome was any major bleeding (defined by the individual studies).

RESULTS:

A total of 13 trials randomizing 164 225 participants with 1 050 511 participant-years of follow-up were included. The median age of trial participants was 62 years (range, 53-74), 77 501 (47%) were men, 30 361 (19%) had diabetes, and the median baseline risk of the primary cardiovascular outcome was 9.2% (range, 2.6%-15.9%). Aspirin use was associated with significant reductions in the composite cardiovascular outcome compared with no aspirin (57.1 per 10 000 participant-years with aspirin and 61.4 per 10 000 participant-years with no aspirin) (hazard ratio [HR], 0.89 [95% credible interval, 0.84-0.95]; absolute risk reduction, 0.38% [95% CI, 0.20%-0.55%]; number needed to treat, 265). Aspirin use was associated with an increased risk of major bleeding events compared with no aspirin (23.1 per 10 000 participant-years with aspirin and 16.4 per 10 000 participant-years with no aspirin) (HR, 1.43 [95% credible interval, 1.30-1.56]; absolute risk increase, 0.47% [95% CI, 0.34%-0.62%]; number needed to harm, 210).

CONCLUSIONS AND RELEVANCE:

The use of aspirin in individuals without cardiovascular disease was associated with a lower risk of cardiovascular events and an increased risk of major bleeding. This information may inform discussions with patients about aspirin for primary prevention of cardiovascular events and bleeding.

Keywords 
aspirin bleeding events cardiovascular events
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