Women's Health Study: Low-Dose Aspirin in Primary Prevention

1. Women's Health Study: Low-Dose Aspirin in Primary Prevention Trial Women's Health Study: Low-Dose Aspirin in Primary Prevention Presented at American College of Cardiology Scientific Sessions 2005 Presented by Dr. Dr. Paul M. Ridker

2. Women's Health Study: Low-Dose Aspirin in Primary Prevention Trial 39,876 initially healthy† women age ≥ 45 Randomized, blinded, factorial Placebo n=19,942 Low-dose Aspirin 100mg on alternate days n=19,934 • Endpoints (mean 10.1 years): • Combined endpoint of nonfatal MI, nonfatal stroke, and total cardiovascular death. • Incidence of total malignant neoplasms of epithelial cell origin. †: No history of coronary heart disease, cerebrovascular disease, cancer (except nonmelanoma skin cancer), or other major chronic illness; no history of side effects to any of the study medications; not taking aspirin or nonsteroidal antiinflammatory medications (NSAIDs) more than once a week (or were willing to forego their use during the trial); not taking anticoagulants or corticosteroids; and not taking individual supplements of vitamin A, E, or beta carotene more than once a week. Presented at ACC Scientific Sessions 2005

3. Women's Health Study: Low-Dose Aspirin in Primary Prevention Trial Composite Components: Primary Composite Endpoint: Major Cardiovascular Events Relative Risk [RR] 0.91 95% CI 0.80-1.03 p=0.13 Death from CV Causes p=0.68 Stroke p=0.04 MI p=0.83 Placebo Placebo Aspirin Aspirin Placebo Aspirin • Baseline characteristics were well matched between the two treatment groups. • Among the individual components of the composite endpoint, there was no difference in MI or death from cardiovascular causes, but total stroke was lower in the aspirin group. Presented at ACC Scientific Sessions 2005

4. Women's Health Study: Low-Dose Aspirin in Primary Prevention Trial Components of Stroke Transient Ischemic Attack p=0.01 Gastrointestinal Bleeding Requiring Transfusion p=0.02 Hemorrhagic Stroke p=0.31 Ischemic Stroke p=0.009 Placebo Placebo Placebo Placebo Aspirin Aspirin Aspirin Aspirin • Total stroke was lower in the aspirin group due to a reduction in ischemic stroke. • Transient ischemic attack was lower in the aspirin group, but there was a higher incidence of gastrointestinal bleeding requiring transfusion. Presented at ACC Scientific Sessions 2005

5. Women's Health Study: Low-Dose Aspirin in Primary Prevention Trial Primary Composite Endpoint (age ≥ 65) p=0.008 Gastrointestinal Bleeding (age ≥ 65) p=0.05 16 44 • In the subgroup analysis, the primary endpoint was lower in women age ≥65 years (n=4097) (RR 0.74, p=0.008), but did not differ in women <65 years (p<0.001 for interaction). • Additionally, the primary endpoint was lower in women who were former or never smokers (RR 0.80, p=0.003) but was higher in current smokers (RR 1.30, p=0.03; p<0.001 for interaction). Presented at ACC Scientific Sessions 2005

6. Women's Health Study: Low-Dose Aspirin in Primary Prevention Trial • Among initially healthy women, treatment with low-dose aspirin was not associated with a significant difference in the primary endpoint of major cardiovascular events compared with placebo at a mean 10 year follow-up. • Low-dose aspirin has been shown to be effective for secondary prevention following acute coronary syndromes, but data for primary prevention with aspirin in women were limited. The Physicians' Health Study, a randomized trial of aspirin for primary prevention conducted in male physicians showed a reduction in MI and a trend toward an increase in total stroke, unlike the present trial in women which showed no difference in MI and a reduction in total stroke. It is unclear why gender-related differences in aspirin therapy for primary prevention may exist. • Benefit with aspirin therapy was observed in the subgroup of women age ≥65 years and non-smokers. Presented at ACC Scientific Sessions 2005