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



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.



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.



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.
Department of Medicine, University of Toronto, Suite RFE 3-805, 200 Elizabeth Street, M5G 2C4, Toronto, Ontario, Canada; Institute for Clinical Evaluative Sciences, G1 06, 2075 Bayview Ave, M4N 3M5, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street, Suite 425, M5T 3M6, Toronto, Ontario, Canada; Women's College Hospital, 76 Grenville Street, M5S1B2, Toronto, Ontario, Canada.
Husam
H
Abdel-Qadir
Department of Medicine, University of Toronto, Suite RFE 3-805, 200 Elizabeth Street, M5G 2C4, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street, Suite 425, M5T 3M6, Toronto, Ontario, Canada; Princess Margaret Cancer Centre, 610 University Ave, M5G 2M9, Toronto, Ontario, Canada.
Eitan
E
Amir
Institute for Clinical Evaluative Sciences, G1 06, 2075 Bayview Ave, M4N 3M5, Toronto, Ontario, Canada.
Hadas D
HD
Fischer
Institute for Clinical Evaluative Sciences, G1 06, 2075 Bayview Ave, M4N 3M5, Toronto, Ontario, Canada.
Longdi
L
Fu
Institute for Clinical Evaluative Sciences, G1 06, 2075 Bayview Ave, M4N 3M5, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street, Suite 425, M5T 3M6, Toronto, Ontario, Canada.
Peter C
PC
Austin
Department of Medicine, University of Toronto, Suite RFE 3-805, 200 Elizabeth Street, M5G 2C4, Toronto, Ontario, Canada; Women's College Hospital, 76 Grenville Street, M5S1B2, Toronto, Ontario, Canada; Women's College Research Institute, 7th Floor, 790 Bay Street, M5G 1N8, Toronto, Ontario, Canada; Peter Munk Cardiac Centre and Joint Department of Medical Imaging, University Health Network, 585 University Ave, M5G 2N2, Toronto, Ontario, Canada.
Paula J
PJ
Harvey
Department of Medicine, University of Toronto, Suite RFE 3-805, 200 Elizabeth Street, M5G 2C4, Toronto, Ontario, Canada; Institute for Clinical Evaluative Sciences, G1 06, 2075 Bayview Ave, M4N 3M5, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street, Suite 425, M5T 3M6, Toronto, Ontario, Canada; Women's College Hospital, 76 Grenville Street, M5S1B2, Toronto, Ontario, Canada; Women's College Research Institute, 7th Floor, 790 Bay Street, M5G 1N8, Toronto, Ontario, Canada.
Paula A
PA
Rochon
Department of Medicine, University of Toronto, Suite RFE 3-805, 200 Elizabeth Street, M5G 2C4, Toronto, Ontario, Canada; Institute for Clinical Evaluative Sciences, G1 06, 2075 Bayview Ave, M4N 3M5, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street, Suite 425, M5T 3M6, Toronto, Ontario, Canada; Peter Munk Cardiac Centre and Joint Department of Medical Imaging, University Health Network, 585 University Ave, M5G 2N2, Toronto, Ontario, Canada.
Douglas S
DS
Lee
Institute for Clinical Evaluative Sciences, G1 06, 2075 Bayview Ave, M4N 3M5, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street, Suite 425, M5T 3M6, Toronto, Ontario, Canada; Women's College Research Institute, 7th Floor, 790 Bay Street, M5G 1N8, Toronto, Ontario, Canada. Electronic address: geoff.anderson@utoronto.ca.
Geoffrey M
GM
Anderson
D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D005260:Female; D006801:Humans; D016247:Information Storage and Retrieval; D016015:Logistic Models; D009203:Myocardial Infarction / Q000453:epidemiology*; D009367:Neoplasm Staging; D009864:Ontario / Q000453:epidemiology; D017698:Postmenopause; D057216:Propensity Score; D016016:Proportional Hazards Models; D012042:Registries; D012307:Risk Factors; D013629:Tamoxifen / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D013629:Tamoxifen
Anastrozole; Cardio-oncology; Coronary artery disease; Endocrine therapy; Exemestane; Hormonal therapy; Letrozole; Survivorship