Cardiovascular Disease After Aromatase Inhibitor Use.

Importance: Cardiovascular disease (CVD) is an important cause of death in older patients with breast cancer. However, limited information exists on the long-term effect of aromatase inhibitor (AI) use on CVD risk in breast cancer survivors. To this point, no other population-based studies have been able to adjust for CVD risk factors or cardiovascular medications.

Objective: To determine the long-term influence of adjuvant endocrine therapies on CVD in a cohort of postmenopausal breast cancer survivors in analyses that accounted for major CVD risk factors, medication use, chemotherapy, and radiotherapy.

Design, Setting, and Participants: A retrospective cohort of postmenopausal women with breast cancer diagnosed from January 1, 1991, to December 31, 2010, and followed up through December 31, 2011 (maximum, 21 years [72 886 person-years]), was evaluated using records from a managed care organization with nearly 20 community hospitals in California. A total of 13 273 postmenopausal women with hormone receptor-positive breast cancer without prior CVD were included. Cardiovascular disease incidence was compared across endocrine therapy categories. Information on demographics, comorbidity, medication, use, and CVD risk was captured from electronic health records. Multivariate Cox proportional hazards models using time-dependent endocrine drug use variables and propensity scores were conducted. Data analysis was conducted from September 15, 2014, to February 1, 2016.

Exposures: Women were grouped by endocrine therapy status (tamoxifen citrate only, AI only, both, or neither).

Main Outcomes and Measures: Person-year rates of CVD for each therapy group.

Results: During 72 886 person-years in 13 273 women (mean [SD] age, 66.8 [8.1] years) with follow-up through 2011, we observed 3711 CVD events. In multivariable analyses (reported as hazard ratio [95% CI]), AI-only users had a similar risk of cardiac ischemia (myocardial infarction and angina) (adjusted, 0.97 [0.78-1.22]) and stroke (adjusted, 0.97 [0.70-1.33]) as tamoxifen-only users (reference). However, we found an increased risk of other CVD (dysrhythmia, valvular dysfunction, and pericarditis) (adjusted, 1.29 [1.11-1.50]) in women who used AIs only or sequentially after tamoxifen (1.26 [1.09-1.45]) vs tamoxifen (reference) as well nonhormone users (1.18 [1.02-1.35]).

Conclusions and Relevance: The risk of the most serious cardiovascular events (cardiac ischemia or stroke) was not elevated in AI-only users compared with tamoxifen users. The finding that other CVD events combined were greater in AI users requires further study.