THE EFFECT OF HORMONE REPLACEMENT THERAPY ALONE AND IN COMBINATION WITH SIMVASTATIN ON PLASMA-LIPIDS OF HYPERCHOLESTEROLEMIC POSTMENOPAUSALWOMEN WITH CORONARY-ARTERY DISEASE

Objectives. This study sought to compare hormone replacement therapy ( HRT), simvastatin and their combination in the management of hyperchol esterolemia in postmenopausal women with coronary artery disease (CAD) , Background. Lipid lowering therapy reduces mortality in hy percholes terolemic women with CAD. In postmenopausal women HRT seems to increas e survival, particularly those with ischemic heart disease, and this i s partly due to changes in lipid levels. Methods. We studied 16 postme nopausal women with CAD and fasting total cholesterol <200 mg/dl and l ow-density lipoprotein (LDL) cholesterol <130 mg/dl, We compared HRT ( 0.625 mg of conjugated estrogen and 2.5 mg of medroxyprogesterone acet ate daily) with simvastatin (20 mg daily) and their combination in a r andomized, crossover, placebo-controlled study. Each treatment period was 8 weeks long with a I-week washout interval between treatments. Re sults. Simvastatin, HRT and their combination significantly reduced to tal and LDL cholesterol by 35%, 13%, and 33% and 45%, 20%, and 46%, re spectively, compared to placebo (p < 0.001). However, simvastatin and the combination was superior to HRT (p < 0.001), and none of our patie nts had total cholesterol <180 mg/dl and LDL cholesterol <100 mg/dl on HRT alone. High-density lipoprotein cholesterol was not significantly affected by any of the active treatments, and triglycerides were lowe r during simvastatin therapy compared to placebo (p < 0.01), Apolipopr otein Ii was significantly reduced by simvastatin, alone and combined with HRT, by 39% and 35%, respectively, compared to placebo (p < 0.001 ). Alone and in combination with simvastatin, HRT significantly increa sed apolipoprotein A-I by 11% and 12%, respectively, compared to place bo (p < 0.05) and decreased lipoprotein (a) by 23% and 33%, respective ly, compared to placebo (p < 0.05), whereas simvastatin had no signifi cant effect on either of these parameters. Conclusions. In hypercholes terolemic postmenopausal women with CAD, HRT exerts beneficial effects on plasma lipids but the levels currently recommended for secondary p revention are not achieved. Hormone replacement therapy combined with simvastatin is well tolerated and extremely effective, as the two ther apies seem to be additive. (C) 1998 by the American College of Cardiol ogy.