Article Title

Cardiovascular Toxicity Following Aromatase Inhibitor Use in 13,273 Women Cared for in an HMO

Publication Date



breast cancer, cardiovascular disease


Background/Aims: Aromatase inhibitors (AIs) reduce breast cancer incidence in primary prevention trials (MAP3, IBIS2). However, controversy regarding AI’s influence on cardiovascular disease (MI, angina and cardiac failure) (Amir et al., J Natl Cancer Inst., 2011) could limit use in prevention settings.

Methods: We assembled a cohort of 13,273 postmenopausal breast cancer patients initially cardiovascular disease (CVD)-free at diagnosis in a large managed care organization. Women were diagnosed 1991–2010, and followed through 2012. The outcome, CVD risk, was compared across endocrine treatments (AI, tamoxifen [TAM], both, or neither). Information on demographics, comorbidity (diabetes, hypertension, etc.) and covariate medications (antihyperlipidemics, antihypertensives and other CVD drugs) were available from electronic medical records. We conducted Cox models using time-dependent endocrine drug use variables adjusted for age, demographics, comorbidity, CVD drug use, cancer treatment, tumor characteristics and tumor laterality.

Results: Among the 13,273-patient cohort, postmenopausal women who used AIs exclusively had a similar risk of ischemic disease (hazard ratio [HR]: 0.97, 95% confidence interval [CI]: 0.78–1.22) and stroke (HR: 0.97, 95% CI: 0.70–1.33) versus those who used TAM only (HR: 1.00, reference). However, women who used AIs only had a higher risk of other CVD disease combined (congestive heart failure, cardiomyopathy, dysrhythmia, valvular dysfunction, pericarditis) (HR: 1.26, 95% CI: 1.11–1.43) than those exposed to TAM only. The risk of other CVD disease was greater among women exposed to sequential TAM and AI treatment. The results are based on 3,711 CVD events occurring in 72,886 woman-years of follow-up. Based on a subset of 7,982 patients who underwent breast irradiation, the risk of CVD overall was greater among women who used AIs only and received left-sided irradiation (HR: 1.21, 95% CI: 1.02–1.44).

Discussion: Results indicate that variation exists in the type of CVD events that occur in breast cancer patients receiving AIs compared to tamoxifen users. For example, the risk of ischemic disease or stroke was not elevated in those who used AIs only versus TAM users. However, overall CVD events were greater in women who used AIs only (or sequentially after TAM), especially if they received left-sided breast irradiation. While these observational study results require cautious interpretation, they provide a basis for comparing the benefits and risks of endocrine treatments.