Coronary Heart Disease and Stroke with Aromatase Inhibitor, Tamoxifen, and Menopausal Hormone Therapy Use

Results from the Women's Health Initiative randomized clinical trials of hormone therapy provide the clinical context for interpreting tamoxifen and aromatase inhibitor (AI) findings regarding coronary heart disease (CHD) and stroke. Of note is the potential link between increased stroke risk and increased dementia risk seen with the use of estrogen alone and the combination of estrogen/progestin. Like hormone therapy, tamoxifen has been found to generally lower low-density lipoprotein and total cholesterol but increase triglyceride levels. The preponderance of clinical evidence suggests that tamoxifen increases stroke risk and has no effect or modestly reduces CHD risk. Aromatase inhibitors generally do not influence low-density lipoprotein cholesterol and could modestly increase high-density lipoprotein cholesterol and reduce triglyceride levels. Current but limited evidence suggests that AIs have a modest increase or no effect on CHD as a class or as individual agents compared with tamoxifen. The influence of AIs on stroke is unsettled, and within-class differences might exist. In the adjuvant breast cancer setting, based on available evidence, the influence of AIs on CHD or stroke will uncommonly influence overall patient outcome. If remaining issues are to be addressed, more rigorous CHD and stroke assessment procedures are needed in future trials evaluating AIs.