Letter by Ren et al Regarding Article, "Aromatase Inhibitors and the Risk of Cardiovascular Outcomes in Women With Breast Cancer: A Population-Based Cohort Study".

Circulation. 2020;142:e156–e157. DOI: 10.1161/CIRCULATIONAHA.120. 047304 e156 Chuanli Ren, MD, PhD Peiheng Li, MD Hou-Zao Chen , MD, PhD To the Editor: We have read the article by Khosrow-Khavar et al1 with great interest, highlighting that aromatase inhibitors (AI) were associated with increased risks of heart failure and cardiovascular mortality compared with tamoxifen in the population-based study. However, inconsistent outcomes were obtained from different populationbased cohorts in different eras.2,3 Kaiser Permanente Southern California study showed that the risk of the most serious cardiovascular events (cardiac ischemia or stroke) was not elevated in AI-only users compared with tamoxifen users.2 The authors claim that their findings are convincing because of the largest observational study directly comparing the risk of cardiovascular disease (CVD) outcomes between AIs and tamoxifen among women with breast cancer,1 whereas the Kaiser Permanente Southern California study may be the longest follow-up study revealing no significant difference of CVD complications.2 We argue that the baseline age and CVD risk assessments are very essential factors influencing the results of different studies. Age is significantly related to CVD, so the risk factors of arteriosclerotic CVD in older patients should have been assessed at least every 5 to 10 years. In addition, AI use was not associated with an increased risk for cardiac ischemia or stroke by stratified analysis of CVD risk factors in the Kaiser Permanente Southern California study.2 The Early Breast Cancer Trialists’ Collaborative Group individual-level meta-analysis displayed that a similar number of women in AI and tamoxifen groups died of CVD, whereas these drugs were associated with favorable clinical outcomes.3 Moreover, the IBIS-II trial (International Breast Cancer Intervention Study II) showed that breast cancer with anastrozole (AIs) can significantly continue to reduce the risk of CVD in the posttreatment follow-up period.4 We argue that it is practical for AI use in breast cancer prevention application because the benefits outweigh its unsettling effects on CVD. The authors restricted their study population to patients at least 55 years of age to minimize the inclusion of premenopausal women.1 However, among the postmenopausal women in AI and tamoxifen trials, there were no significant difference of benefits in the rate ratio by age.3 Furthermore, the Kaiser Permanente Southern California study drew a completely different conclusion using the same age standard.2 We wonder whether their findings would have more clinical guiding significance if participants under 55 years were included in the trial to compare incidence of CVD between AIs and tamoxifen among younger women with breast cancer. We propose that a larger population and longer follow-up data are needed to find out the real benefits of AI among women of all ages with breast cancer. We argue that the inconsistent results may be attributed to different amounts of median follow-up time and different eras, in part resulting in insufficient information to evaluate the quality of different studies.5 We know that the increase of CVD © 2020 American Heart Association, Inc. LETTER TO THE EDITOR