Abstract 2181: Risk of Stroke in the Raloxifene Use for The Heart (RUTH) Trial
Introduction: In the RUTH trial, raloxifene, a selective estrogen receptor modulator, had no effect on risk for coronary heart disease (CHD) and decreased the risk of invasive breast cancer. The purpose of this analysis was to determine raloxifene’s effect on stroke risk and in various subgroups.
Methods: 10,101 postmenopausal women with or at increased risk of CHD were randomized to raloxifene 60 mg daily or placebo and followed a median of 5.6 years. Stroke, a pre-specified secondary endpoint, was defined as the rapid onset of a persistent neurological defect lasting >24 hours, adjudicated by an expert committee, was categorized as ischemic, hemorrhagic, or undetermined. Analyses were based on intention to treat and time to event methods. Eighteen pre-specified subgroup analyses were performed based on patient characteristics, co-morbidities, and medication use.
Results: Risk for all strokes was not different in the raloxifene group (N=249) compared to the placebo group (N=224). Raloxifene was associated with an increased risk of fatal stroke compared to placebo (59 vs 39, p=0.05; absolute risk increase 0.7 per 1000 women treated for 1 year). The increased risk emerged after 3 years and remained constant thereafter (Figure⇓). There were no significant (p>0.1) differences in treatment effect by subgroup except for smoking and all strokes (p=0.09).
Conclusion: In RUTH, raloxifene had no impact on overall stroke risk but increased the risk of fatal stroke. The risk-benefit ratio of raloxifene in postmenopausal women with a history of stroke or other significant risk factors for stroke should be considered when making treatment decisions about raloxifene.