Aspirin for Primary Prevention of Vascular Events in Women: Individualized Prediction of Treatment Effects
Do individual patient characteristics identify women who would benefit from aspirin 100 mg every other day for primary prevention of vascular events?
Data from the Women’s Health Study (WHS), a randomized controlled trial of aspirin for primary prevention of vascular events, were used in the present analysis. The WHS evaluated the effect of 100 mg of aspirin on alternate days when compared with placebo on the occurrence of major cardiovascular events (i.e., nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) among 39,876 initially healthy women 45 years of age or older. After a mean follow-up of 10.1 years, the hazard ratio for occurrence of the primary endpoint was 0.91 (95% confidence interval [CI], 0.80-1.03). Aspirin treatment was associated with increased risk for gastrointestinal bleeding (relative risk [RR], 1.22; 95% CI, 1.10-1.34), peptic ulcer (RR, 1.32; 95% CI, 1.16-1.50), haematuria (RR, 1.06; 95% CI, 1.01-1.12), easy bruising (RR, 1.40; 95% CI, 1.37-1.45), and epistaxis (RR, 1.16; 95% CI, 1.11-1.22). Women eligible for the current analysis were those who provided an adequate baseline plasma sample. Predictions were based on existing risk scores, such as Framingham (FRS), and Reynolds (RRS) risk scores, and on a newly developed prediction model. The net benefit of different aspirin treatment strategies was compared: (i) treat no one, (ii) treat everyone, (iii) treatment according to the current guidelines (i.e., selective treatment of women 65 years of age or having 0.10% FRS), and (iv) prediction-based treatment (i.e., selective treatment of patients whose predicted treatment effect exceeds a given decision threshold).
A total of 27,939 women were included in this analysis. On average, women were at low baseline risk for cardiovascular disease, with a mean 10-year risk for cardiovascular events of 2.9%. The predicted reduction in 10-year absolute risk for major cardiovascular events was 1% in the majority of women (97% of the cohort) based on the adjusted FRS. A similar result was observed when the RRS was used. The 10-year absolute risk for major cardiovascular disease events was 1% in 90% of women when the newly developed model was used. Of the treatment strategies considered, only prediction-based treatment using the newly developed model and selective treatment of women >65 years of age yielded more net benefit than treating no one, provided that the 10-year number-willing-to-treat to prevent one cardiovascular event was above 50.
The investigators concluded that aspirin was ineffective or harmful in the majority of women. Age was positively related to treatment effect, whereas current smoking and baseline risk for cardiovascular events were not.
This current analysis allows clinicians to provide a more detailed discussion of the risks and benefits of aspirin in women for primary prevention, and supports current prevention guidelines, which recommend aspirin (75-325 mg per day) for women at high risk for cardiovascular events, including those with a prior history of coronary heart disease, unless contraindicated. Aspirin is also reasonable for women with diabetes mellitus (unless contraindicated). Current guidelines also suggest that aspirin may be beneficial for women 65 years or older (either 80 mg/day or 100 mg every other day) if risk of ischemic stroke or myocardial infarction is greater than risk of hemorrhagic stroke or gastrointestinal bleeding, unless contraindications including uncontrolled hypertension are present.
Keywords: Myocardial Infarction, Stroke, Follow-Up Studies, Platelet Aggregation Inhibitors, Women's Health, Coronary Disease, Gastrointestinal Hemorrhage, Epistaxis, Smoking, Primary Prevention, Cardiovascular Diseases, Peptic Ulcer, Confidence Intervals, Risk Assessment, Hypertension, Diabetes Mellitus
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