The risk of myocardial infarction with aromatase inhibitors relative to tamoxifen in post-menopausal women with early stage breast cancer

Abstract

Background: Aromatase inhibitors (AIs) may increase cardiovascular risk relative to tamoxifen in post-menopausal women with breast cancer. This risk has not been well-quantified outside of clinical trials.

Methods: Observational population-based cohort study of women aged >55 years diagnosed with stage I-III breast cancer between 2005 and 2010. Women treated with AIs or tamoxifen were followed to March 2012. The primary outcome was hospitalisation for myocardial infarction (MI). Cause-specific hazards were compared using tamoxifen as the reference group. Inverse probability of treatment weighting using the propensity score was used to reduce confounding due to measured baseline covariates. Results were confirmed using two cause-specific hazards models. Subgroup analyses included women aged ≥66 years, those with prior ischaemic heart disease, and a 'lower-risk group' aged <74 years with stage I-II cancer and no prior ischaemic heart disease.

Results: In 7409 aromatase inhibitor-treated and 1941 tamoxifen-treated women, the median age was 71 versus 74 years, respectively (p < 0.001). Baseline prevalence of ischaemic heart disease was similar (17.0% versus 16.9%, p = 0.96). Over a mean of 1184 d of follow-up, there were 123 hospitalisations for MI; the cause-specific hazard was higher with AIs (hazard ratio 2.02; 95% confidence interval 1.16-3.53 in the weighted sample). We observed comparable patterns within pre-defined subgroups and when adjusted using cause-specific hazards models.

Conclusion: Aromatase inhibitors are associated with a higher risk of MI compared with tamoxifen. This risk should be accounted for when managing aromatase inhibitor-treated women.

Keywords: Anastrozole; Cardio-oncology; Coronary artery disease; Endocrine therapy; Exemestane; Hormonal therapy; Letrozole; Survivorship.