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

Kisho Ohtani, Tomomi Ide, Ken ichi Hiasa, Ichiro Sakamoto, Nami Yamashita, Makoto Kubo, Hiroyuki Tsutsui

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)1128-1139
Number of pages12
JournalClinical Research in Cardiology
Volume108
Issue number10
DOIs
Publication statusPublished - Oct 1 2019

Fingerprint

Anthracyclines
Left Ventricular Dysfunction
Breast Neoplasms
Heart Failure
Cardiotoxicity
Trastuzumab
Treatment Failure
Stroke Volume
Multivariate Analysis
Therapeutics

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Cardioprotective effect of renin–angiotensin inhibitors and β-blockers in trastuzumab-related cardiotoxicity. / Ohtani, Kisho; Ide, Tomomi; Hiasa, Ken ichi; Sakamoto, Ichiro; Yamashita, Nami; Kubo, Makoto; Tsutsui, Hiroyuki.

In: Clinical Research in Cardiology, Vol. 108, No. 10, 01.10.2019, p. 1128-1139.

Research output: Contribution to journalArticle

@article{97fe1a5d6c1b4c56b146b77761cbf333,
title = "Cardioprotective effect of renin–angiotensin inhibitors and β-blockers in trastuzumab-related cardiotoxicity",
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.",
author = "Kisho Ohtani and Tomomi Ide and Hiasa, {Ken ichi} and Ichiro Sakamoto and Nami Yamashita and Makoto Kubo and Hiroyuki Tsutsui",
year = "2019",
month = "10",
day = "1",
doi = "10.1007/s00392-019-01448-4",
language = "English",
volume = "108",
pages = "1128--1139",
journal = "Clinical Research in Cardiology",
issn = "1861-0684",
publisher = "D. Steinkopff-Verlag",
number = "10",

}

TY - JOUR

T1 - Cardioprotective effect of renin–angiotensin inhibitors and β-blockers in trastuzumab-related cardiotoxicity

AU - Ohtani, Kisho

AU - Ide, Tomomi

AU - Hiasa, Ken ichi

AU - Sakamoto, Ichiro

AU - Yamashita, Nami

AU - Kubo, Makoto

AU - Tsutsui, Hiroyuki

PY - 2019/10/1

Y1 - 2019/10/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85071299206&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85071299206&partnerID=8YFLogxK

U2 - 10.1007/s00392-019-01448-4

DO - 10.1007/s00392-019-01448-4

M3 - Article

AN - SCOPUS:85071299206

VL - 108

SP - 1128

EP - 1139

JO - Clinical Research in Cardiology

JF - Clinical Research in Cardiology

SN - 1861-0684

IS - 10

ER -