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Prevention of Trastuzumab and Anthracycline-induced Cardiotoxicity Using Angiotensin-converting Enzyme Inhibitors or β-blockers in Older Adults With Breast Cancer

Wittayanukorn, Saranrat, PhD*; Qian, Jingjing, PhD*; Westrick, Salisa C., PhD*; Billor, Nedret, PhD; Johnson, Brandon, MD‡,§; Hansen, Richard A., PhD*

American Journal of Clinical Oncology: September 2018 - Volume 41 - Issue 9 - p 909–918
doi: 10.1097/COC.0000000000000389
Original Articles: Breast

Purpose: Although clinical trials have provided some data on the benefit of angiotensin-converting enzyme inhibitors (ACEIs) or β-blockers (BBs) in patients with chemotherapy-induced cardiotoxicity, evidence of ACEIs/BBs on prevention of trastuzumab and/or anthracycline-induced cardiotoxicity outside trials is limited.

Materials and Methods: A cohort study of 142,990 women (66 y and above) newly diagnosed with breast cancer from 2001 to 2009 was conducted using the Surveillance, Epidemiology, and End Results-Medicare–linked database. The ACEI/BB exposure was defined as filled prescription(s) before or after the initiation of trastuzumab/anthracyclines. The nonexposed group was defined as those who had never been prescribed ACEIs/BBs. Cumulative rates of cardiotoxicity and all-cause mortality were estimated and marginal structural Cox models were used to determine factors associated with cardiotoxicity and all-cause mortality adjusting for baseline covariates and use of chemotherapy. All statistical tests were 2 sided.

Results: The final sample included 6542 women. Adjusted hazard ratio for cardiotoxicity and all-cause mortality for the ACEI/BB exposed group were 0.77 (95% confidence interval, 0.62-0.95) and 0.79 (95% confidence interval, 0.70-0.90) compared with the nonexposed group, respectively. Starting ACEIs/BBs≤6 months after the initiation of trastuzumab/anthracyclines and having exposed duration≥6 months were also associated with decreased risk of cardiotoxicity and all-cause mortality. Baseline characteristics, including age, non-Hispanic black, advanced cancer, region, comorbidity, preexisting cardiovascular conditions, lower socioeconomic status, and concomitant treatment were significantly associated with an elevated risk of all-cause mortality and/or cardiotoxicity (all P<0.05).

Conclusions: ACEIs/BBs show favorable effects on preventing cardiotoxicity and improving survival in female breast cancer patients undergoing trastuzumab/anthracycline treatment.

*Harrison School of Pharmacy

College of Sciences and Mathematics, Auburn University

East Alabama Medical Center

§Department of Internal Medicine, Edward via College of Osteopathic Medicine, Auburn, AL

S.W. is supported by an Auburn University Research Initiative in Cancer (AURIC) fellowship.

In the past 3 years R.A.H. has received consulting fees from Novartis and Daiichi Sankyo. The other authors declare no conflicts of interest.

Reprints: Saranrat Wittayanukorn, PhD, Department of Health Outcomes Research and Policy, Auburn University Harrison School of Pharmacy, 020 James E Foy Hall, Auburn, AL 36849-5506. E-mail:

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