Lisinopril or Carvedilol for Prevention of Trastuzumab Induced Cardiotoxicity - Lisinopril or Carvedilol for Cardiotoxicity

Jun 03, 2019
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Author/Summarized by Author:
Anthony A. Bavry, MD,MPH,FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
University of South Florida, National Cancer Institute
Date Presented:
03/11/2018
Date Published:
06/03/2019
Date Updated:
06/03/2019
Original Posted Date:
03/11/2018
References

Contribution To Literature:

The Lisinopril or Carvedilol for Cardiotoxicity trial failed to show that lisinopril or carvedilol was superior to placebo at preventing left ventricular systolic dysfunction.

Description:

The goal of the trial was to evaluate lisinopril versus carvedilol versus placebo for prevention of cardiomyopathy among patients undergoing trastuzumab chemotherapy for breast cancer.

Study Design

  • Randomized
  • Parallel
  • Stratified
  • Placebo
  • Blinded

Patients with breast cancer undergoing trastuzumab chemotherapy were randomized to lisinopril versus carvedilol versus placebo. Patients were stratified by treatment with an anthracycline. Baseline left ventricular ejection fraction (LVEF) was 63%.

  • Total number of enrollees: 468
  • Duration of follow-up: 24 months
  • Mean patient age: 51 years
  • Percentage female: 50%

Inclusion criteria:

  • Patients ≥18 years of age
  • HER2-positive breast cancer
  • Planned trastuzumab chemotherapy
  • Baseline LVEF: ≥50%
  • Normal renal and hepatic function
  • Systolic blood pressure: >90 mm Hg
  • Heart rate: ≥60 bpm

Exclusion criteria:

  • Current treatment with angiotensin-converting enzyme inhibitor, angiotensin-receptor blocker, beta-blocker, or digoxin
  • Metastatic disease
  • Prior cardiac disease
  • Prior asthma
  • History of angioedema
  • Pregnant or breastfeeding

Principal Findings:

The primary outcome, decrease in LVEF >10%, occurred in 30% of the lisinopril group vs. 29% of the carvedilol group vs. 32% of the placebo group (p = not significant). Among those on anthracyclines, decrease in LVEF >10%, occurred in 37% of the lisinopril group vs. 31% of the carvedilol group vs. 47% of the placebo group.

Among those not on an anthracycline, the average change of mean LVEF was -3.2 mm Hg in the carvedilol group and (p = 0.64 vs. placebo) -2.3 mm Hg in the lisinopril group (p = 0.68 vs. placebo).

Among those on an anthracycline, the average change of mean LVEF was -4.5 mm Hg in the carvedilol group (p = 0.008 vs. placebo) and -4.0 mm Hg in the lisinopril group (p = 0.002 vs. placebo).

Secondary outcomes: Trastuzumab interruption was the same between treatment groups.

Interpretation:

Among patients with breast cancer undergoing chemotherapy with trastuzumab, neither lisinopril nor carvedilol was effective at preventing cardiomyopathy compared with placebo. However, among those who were treated with an anthracycline, lisinopril and carvedilol appeared to be effective at preventing cardiomyopathy versus placebo. Study medication did not prevent trastuzumab discontinuation. Further study of this important problem is warranted.

References:

Guglin M, Krischer J, Tamura R, et al. Randomized Trial of Lisinopril Versus Carvedilol to Prevent Trastuzumab Cardiotoxicity in Patients With Breast Cancer. J Am Coll Cardiol 2019;73:2859-68.

Editorial Comment: Barac A, Blaes A, Lynce F. Lessons From Primary Cardiac Prevention Trials During Trastuzumab Therapy: End of One Size Fits All. J Am Coll Cardiol 2019;73:2869-71.

Presented by Dr. Maya E. Guglin at the American College of Cardiology Annual Scientific Session (ACC 2018), Orlando, FL, March 11, 2018.

Keywords: ACC18, ACC Annual Scientific Session, Anthracyclines, Blood Pressure, Breast Neoplasms, Cardiomyopathies, Cardiotoxicity, Chemotherapy, Adjuvant, Heart Failure, Heart Rate, Lisinopril, Primary Prevention, Stroke Volume, Women


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