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Cardioprotective effect of renin–angiotensin inhibitors and β-blockers in trastuzumab-related cardiotoxicity

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Abstract

Background

Trastuzumab-related cardiotoxicity (TRC) has been considered as reversible. However, recent studies have raised concern against reversibility of left ventricular (LV) systolic dysfunction in breast cancer patients treated with trastuzumab. In addition, the efficacy of medical treatment for heart failure (HF) including renin–angiotensin inhibitors and β-blockers has not been defined in TRC.

Methods and results

We retrospectively studied 160 patients with breast cancer receiving trastuzumab in the adjuvant (n = 129) as well as metastatic (n = 31) settings in our institution from 2006 to 2015. During the median follow-up of 3.5 years, 20 patients (15.5%) receiving adjuvant trastuzumab and 7 patients (22.6%) with metastatic breast cancer developed TRC with a mean decrease in LV ejection fraction (EF) of 19.8%. By the multivariate analysis, lower LVEF before trastuzumab (OR 1.30; 95% CI 1.16–1.48; P = 0.0001) independently predicted subsequent development of TRC. LV systolic dysfunction was reversible in 20 patients (74.1%) with a median time to recovery of 7 months, which was independently associated with lower dose of anthracyclines (OR 1.03; 95% CI 1.01–1.07, P = 0.020) and an introduction of renin–angiotensin inhibitors and β-blockers (OR 19.0; 95% CI 1.00–592.2, P = 0.034).

Conclusions

Irreversible decline in LVEF occurred in patients who underwent trastuzumab in combination with anthracyclines with a relatively high frequency. The lower cumulative dose of anthracyclines and HF treatment including renin–angiotensin inhibitors and β-blockers were both independent predictors to enhance LV functional reversibility in patients with TRC.

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Acknowledgements

We thank Chie Tada, Youko Matsuura, Gorou Kawahara, Shiori Horikawa, Tokiko Hirakawa, Sayaka Ohtake, Tasuku Satoh, Aki Katsuki, Maki Tsutsumi, Asami Hanada, Nami Kuwano for the assistance in echocardiographic data collection.

Funding

This study was supported by Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (K.O., T.I.).

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Kisho Ohtani, Tomomi Ide, Ken-ichi Hiasa, Ichiro Sakamoto & Hiroyuki Tsutsui

  2. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Nami Yamashita

  3. Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Makoto Kubo

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  1. Kisho Ohtani
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Correspondence to Kisho Ohtani.

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Dr. Tsutsui has received the research grant from Actelion, Daichii-Sankyo, and Astellas, and lecture fees from Astellas, Otsuka, Takeda, Daichii-Sankyo, Mitsubishi Tanabe, Boehringer Ingelheim, Novartis, Bayer, and Bristol-Myers Squibb.

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Ohtani, K., Ide, T., Hiasa, Ki. et al. Cardioprotective effect of renin–angiotensin inhibitors and β-blockers in trastuzumab-related cardiotoxicity. Clin Res Cardiol 108, 1128–1139 (2019). https://doi.org/10.1007/s00392-019-01448-4

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