BACKGROUND

The Raloxifene Use for The Heart (RUTH) trial showed that raloxifene, a selective estrogen receptor modulator, had no overall effect on the incidence of coronary events in women with established coronary heart disease or coronary heart disease risk factors. We provide detailed results of the effect of raloxifene on coronary outcomes over time and for 24 subgroups (17 predefined, 7 post hoc).

METHODS AND RESULTS

Postmenopausal women (n=10 101; mean age, 67 years) were randomized to raloxifene 60 mg/d or placebo for a median of 5.6 years. Coronary outcomes were assessed by treatment group in women with coronary heart disease risk factors and those with established coronary heart disease. Raloxifene had no effect on the incidence of coronary events in any subgroup except in the case of a post hoc age subgroup analysis using age categories defined in the Women's Health Initiative randomized trials. The effect of raloxifene on the incidence of coronary events differed significantly by age (interaction P=0.0118). The incidence of coronary events in women <60 years of age was significantly lower in those assigned raloxifene (50 events) compared with placebo (84 events; hazard ratio, 0.59; 95% confidence interval, 0.41 to 0.83; P=0.003; absolute risk reduction, 36 per 1000 women treated for 1 year). No difference was found between treatment groups in the incidence of coronary events in women > or =60 and <70 or > or =70 years of age.

CONCLUSIONS

In postmenopausal women at increased risk of coronary events, the overall lack of benefit of raloxifene was similar across the prespecified subgroups.

Among hepatitis C patients, lack of cirrhosis and sustained virologic response (SVR) reduce the risk of hepatocellular carcinoma (HCC). Japanese studies document multiple cases of HCC among these patients, but only one case has been reported outside of Asia. We identified five patients with hepatitis C in our university-based hepatology practice who developed HCC despite SVR and lack of cirrhosis on their pretreatment liver biopsy. At the time of HCC diagnosis, two remained noncirrhotic, one had clearly progressed to cirrhosis, and two lacked repeat histology. We present these patients in a case series format and discuss several important implications of their cases. Physicians often base screening and treatment decisions on an initial liver biopsy performed years earlier. As fibrosis may advance, and because SVR and lack of cirrhosis do not fully protect against HCC, future study should further evaluate the risk of HCC among hepatitis C patients after sustained virologic response.