Postmenopausal hormone replacement therapy and the primary prevention of cardiovascular disease

Purpose: To evaluate the value of hormone replacement therapy (HRT) in the primary prevention of cardiovascular disease (CVD) and coronary artery disease (CAD). Data Sources: MEDLINE and Cochrane databases were searched for all primary prevention studies reporting CVD or CAD incidence, mortality, or both in association with HRT; reference lists, letters, editorials, and reviews were also reviewed. Data Extraction: All studies were reviewed, abstracted, and rated for quality. Study Selection: Only studies of good or fair quality, according to U.S. Preventive Services Task Force (USPSTF) criteria, were included in the detailed review and meta-analysis. Data Synthesis: The summary relative risk with any HRT use was 0.75 (95% credible interval [Crl], 0.42 to 1.23) for CVD mortality and 0.74 (Crl, 0.36 to 1.45) for CAD mortality. The summary relative risk with any use was 1.28 (Crl, 0.86 to 2.00) for CVD incidence and 0.87 (Crl, 0.62 to 1.21) for CAD incidence. Further analysis of studies adjusting for socioeconomic status, as well as other major CAD risk factors, showed a summary relative risk of 1.07 (Crl, 0.79 to 1.48) for CAD incidence associated with any HRT use. Similar results were found when the analysis was stratified by studies adjusting for alcohol consumption, exercise, or both, in addition to other major risk factors, suggesting confounding by these factors. Conclusions: This meta-analysis differs from previous meta-analyses by evaluating potential explanatory variables of the relationship between HRT, CVD, and CAD. The adjusted meta-analysis is consistent with recent randomized trials that have shown no benefit in the secondary or primary prevention of CVD events. A valid answer to the role of HRT in the primary prevention of CVD will best come from randomized, controlled trials.