In the Scandinavian Simvastatin Survival Study (4S), 3617 men and 827 women with angina or previous MI and mean LDL cholesterol level of 4.86 mmol/L (188 mg/dL) (total cholesterol level ranging from 5.48 to 7.99 mmol/L [212 to 309 mg/dL]) were randomized to receive simvastatin, 20 mg/d (titrated to 40 mg/d if necessary to lower total cholesterol level to <5.17 mmol/L [<200 mg/dL]) vs placebo.69 At median follow-up of 5.4 years, simvastatin lowered LDL cholesterol levels by 37.4% in women and significantly reduced the risk of the combined end point (all-cause mortality, CHD death, nonfatal MI, or resuscitated cardiac arrest) by 34% in both women and men. The need for CABG or PTCA was reduced by 49% in women (95% CI, 0.30-0.86). Both CHD and total mortality were significantly reduced in men; however, there was no significant reduction in CHD mortality and no benefit on total mortality in women (RR, 1.16; 95% CI, 0.68-1.99), a finding related to the lower total and CHD mortality of 6% and 4%, respectively, in women in the placebo group compared with 13% and 8%, respectively, in men. One potential reason for the lack of mortality differences is that women were more likely than men to be enrolled for only angina (37% vs 17%). Since chest pain in women is less likely to be associated with marked epicardial stenoses than in men, a majority of women with only angina in the Scandinavian Simvastatin Survival Study may not have had coronary artery disease as a cause of their chest pain. These sex differences must be considered when results of clinical trials that enrolled patients on the basis of a history of angina rather than MI or diagnostically confirmed CHD are interpreted.