Efficacy of Neurohormonal Therapies in Preventing Cardiotoxicity in Patients with Cancer Undergoing Chemotherapy

Muthiah Vaduganathan; Sameer A Hirji; Arman Qamar; Navkaranbir Bajaj; Ankur Gupta; Vlad Zaha; Alvin Chandra; Mark Haykowsky; Bonnie Ky; Javid Moslehi; Anju Nohria; Javed Butler; Ambarish Pandey

doi:10.1016/j.jaccao.2019.08.006

Efficacy of Neurohormonal Therapies in Preventing Cardiotoxicity in Patients with Cancer Undergoing Chemotherapy

JACC CardioOncol. 2019 Sep;1(1):54-65. doi: 10.1016/j.jaccao.2019.08.006. Epub 2019 Sep 24.

Authors

Muthiah Vaduganathan¹, Sameer A Hirji², Arman Qamar³, Navkaranbir Bajaj⁴, Ankur Gupta⁵, Vlad Zaha⁵, Alvin Chandra^{1

5}, Mark Haykowsky⁶, Bonnie Ky⁷, Javid Moslehi⁸, Anju Nohria¹, Javed Butler⁹, Ambarish Pandey⁵

Affiliations

¹ Brigham and Women's Hospital Heart & Vascular Center & Harvard Medical School, Boston, MA.
² Division of Cardiac Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
³ TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
⁴ University of Alabama at Birmingham, Birmingham, AL.
⁵ Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX.
⁶ College of Nursing and Health Innovation, University of Texas at Arlington, Arlington, TX.
⁷ Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
⁸ Cardio-Oncology Program, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
⁹ Department of Medicine, University of Mississippi, Jackson, MS.

Abstract

Background: Various cardioprotective approaches have been evaluated to prevent chemotherapy-related cardiotoxicity; however, their overall utility remains uncertain.

Objectives: To assess the effects of neurohormonal therapies in preventing cardiotoxicity in patients receiving chemotherapy.

Methods: This meta-analysis included randomized clinical trials of adult patients that underwent chemotherapy and neurohormonal therapies (beta-blockers, mineralocorticoid receptor antagonists, or ACE inhibitors/ARBs) vs. placebo with follow-up ≥4 weeks. The primary outcome was change in left ventricular ejection fraction (LVEF) from baseline to the end of trial. Other outcomes of interest were measures of LV size, strain, and diastolic function. Pooled estimates for each outcome were reported as standardized mean difference (SMD) and weighted mean difference (WMD) between the neurohormonal therapy and placebo groups using random effects models.

Results: We included 17 trials, collectively enrolling 1,984 participants. In pooled analysis, neurohormonal therapy (vs. placebo) was associated with significantly higher LVEF on follow-up [SMD(95% CI): +1.04(0.57 to 1.50)] but with significant heterogeneity in the pooled estimate (I² = 96%). Compared with placebo-treated patients, those randomized to neurohormonal therapies experienced a 3.96% (95%CI: 2.9% to 5.0%) less decline in LVEF estimated by WMD, but with significant heterogeneity (I² = 98%). There was a trend towards lower adverse clinical events with neurohormonal therapy (vs. placebo) without statistical significance [risk ratio(95%CI): 0.80(0.53-1.20) I² = 71%].

Conclusions: Neurohormonal therapies are associated with higher LVEF in follow-up among cancer patients receiving chemotherapy, although absolute changes in LVEF are small and may be within inter-test variability. Furthermore, significant heterogeneity is observed in the treatment effects across studies highlighting the need for larger trials of cardioprotective strategies.

Keywords: cardio-oncology; cardiotoxicity; ejection fraction; heart failure; meta-analysis.

Abstract

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