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

Muthiah Vaduganathan, MD, MPH; Sameer A. Hirji, MD, MPH; Arman Qamar, MD; Navkaranbir Bajaj, MD, MPH; Ankur Gupta, MD, PhD; Vlad G. Zaha, MD; Alvin Chandra, MD; Mark Haykowsky, PhD; Bonnie Ky, MD, MSCE; Javid Moslehi, MD; Anju Nohria, MD; Javed Butler, MD, MPH, MBA; Ambarish Pandey, MD, MSCS

JACC. CardioOncology (Sep 2019)

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

Muthiah Vaduganathan, MD, MPH,
Sameer A. Hirji, MD, MPH,
Arman Qamar, MD,
Navkaranbir Bajaj, MD, MPH,
Ankur Gupta, MD, PhD,
Vlad G. Zaha, MD,
Alvin Chandra, MD,
Mark Haykowsky, PhD,
Bonnie Ky, MD, MSCE,
Javid Moslehi, MD,
Anju Nohria, MD,
Javed Butler, MD, MPH, MBA,
Ambarish Pandey, MD, MSCS

Affiliations

Muthiah Vaduganathan, MD, MPH: Brigham and Women’s Hospital Heart, Vascular Center, and Harvard Medical School, Boston, Massachusetts
Sameer A. Hirji, MD, MPH: Division of Cardiac Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
Arman Qamar, MD: TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
Navkaranbir Bajaj, MD, MPH: University of Alabama at Birmingham, Birmingham, Alabama
Ankur Gupta, MD, PhD: Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas
Vlad G. Zaha, MD: Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas
Alvin Chandra, MD: Brigham and Women’s Hospital Heart, Vascular Center, and Harvard Medical School, Boston, Massachusetts; Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas
Mark Haykowsky, PhD: College of Nursing and Health Innovation, University of Texas at Arlington, Arlington, Texas
Bonnie Ky, MD, MSCE: Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
Javid Moslehi, MD: Cardio-Oncology Program, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
Anju Nohria, MD: Brigham and Women’s Hospital Heart, Vascular Center, and Harvard Medical School, Boston, Massachusetts
Javed Butler, MD, MPH, MBA: Department of Medicine, University of Mississippi, Jackson, Mississippi
Ambarish Pandey, MD, MSCS: Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas; Address for correspondence: Dr. Ambarish Pandey, Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390.

Journal volume & issue: Vol. 1, no. 1
pp. 54 – 65

Abstract

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Objectives: This study sought to assess the effects of neurohormonal therapies in preventing cardiotoxicity in patients receiving chemotherapy. Background: Various cardioprotective approaches have been evaluated to prevent chemotherapy-related cardiotoxicity; however, their overall utility remains uncertain. Methods: This meta-analysis included randomized clinical trials of adult patients that underwent chemotherapy and neurohormonal therapies (β-blockers, mineralocorticoid receptor antagonists, or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers) versus placebo with follow-up ≥4 weeks. The primary outcome was change in left ventricular ejection fraction (LVEF) from baseline to the end of the 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 and weighted mean difference 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 (standardized mean difference: +1.04 [95% confidence interval (CI): 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: 2.90 to 5.02) less decline in LVEF estimated by weighted mean difference, but with significant heterogeneity (I2 = 98%). There was a trend toward lower adverse clinical events with neurohormonal therapy (vs. placebo) that did not meet statistical significance (risk ratio: 0.80 [95% CI: 0.53 to 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.

Published in JACC. CardioOncology

ISSN: 2666-0873 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the circulatory (Cardiovascular) system; Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/jacc-cardiooncology

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