Women who were taking a statin agent had a 21 percent lower risk of myocardial infarction and death related to heart disease and a 33 percent lower risk of dying from any cause during four years of treatment compared with women who did not take statins. Statin therapy was also associated with a 55 percent lower risk of venous thromboembolism.

"These data add substantial additional support for use of statins in women with heart disease," says David Herrington, M.D., M.H.S., lead author of the report. "Our results help clarify residual concerns about the true magnitude of statins' benefit in women, because three previous clinical trials had produced somewhat divergent results."

Herrington's team reviewed data from the Heart and Estrogen/progestin Replacement Study (also called HERS). The primary purpose of the study was to evaluate the effect of hormone replacement therapy on myocardial infarction and death rates in 2,763 women with coronary heart disease. The principal finding of the study showed no overall effect of hormone replacement therapy on coronary risk.

In their reanalysis of study data, researchers looked specifically at the outcomes of 1,004 women who were taking a statin drug when they entered the study, as well as 708 women who began statin therapy during the trial. They found that women taking a statin drug at baseline or at any time during the trial had significantly fewer first-time coronary heart disease events than those who did not take a statin drug.

Women in the study who took a statin for at least three years had a 26 percent lower rate of myocardial infarction and coronary death. Statin use for less than three years was associated with a more modest 11 percent risk reduction when compared with risk for non-statin users. Death from any cause was 30 percent lower in women who used a statin at any time during the trial.

Statin drugs have a well-established ability to reduce heart disease risk in men, but until recently the effects in women were less clear, says Herrington. Earlier studies of statin therapy included relatively few women, and the benefits found in women varied widely. The study on which their analysis was based was unique because of the large number of women available for evaluation. (Subsequent to this study, a preliminary summary from the large Heart Protection Study reported significant risk reductions for coronary heart disease in women taking 40 mg/day of simvastatin.)

Herrington wanted to reexamine the data to clarify the effects of statins on cardiovascular events in women and to examine the combined effects of statins and hormone replacement therapy on deaths due to myocardial infarction in postmenopausal women.

Mirroring the primary findings of the trial as a whole, the statin analysis showed that hormone replacement users who were not taking a statin had an especially high risk for coronary events during the first year of the trial -- 75 percent higher than the risk for the placebo group. In contrast, women who were on hormone replacement therapy and a statin during the first year had the same risk of adverse events as women taking placebo.

"The data suggest that statins might help diminish the adverse effects of hormone replacement therapy, but the finding needs to be confirmed in other studies," says Herrington.

To evaluate the impact of a high rate of statin use in the placebo group, the researchers reanalyzed data after excluding both women who started statin therapy during the trial and women who took statin agents before and during the trial. After statistically adjusting for an imbalance in statin use between the treatment and placebo groups, they still did not find a benefit for hormone replacement therapy.

"This study shows that increased statin use in the placebo group did not explain the null finding [of the HERS trial]," says Herrington.