Prophylaxis to Prevent Cardiotoxicity in Patients Receiving Anthracycline for Breast Cancer: A Combined Bayesian and Frequentist Network Meta-Analysis of Randomised Controlled Trials

Prajith Jeyaprakash; Sukhman Sangha; Gary Low; Christopher Yu; Faraz Pathan; Kazuaki Negishi

doi:10.1016/j.hlc.2023.11.004

Prophylaxis to Prevent Cardiotoxicity in Patients Receiving Anthracycline for Breast Cancer: A Combined Bayesian and Frequentist Network Meta-Analysis of Randomised Controlled Trials

Heart Lung Circ. 2024 May;33(5):710-720. doi: 10.1016/j.hlc.2023.11.004. Epub 2024 Jan 5.

Authors

Prajith Jeyaprakash¹, Sukhman Sangha¹, Gary Low², Christopher Yu¹, Faraz Pathan¹, Kazuaki Negishi³

Affiliations

¹ Department of Cardiology, Nepean Hospital, Sydney, NSW, Australia; Department of Academic Medicine, Sydney Medical School Nepean, Faculty of Medicine and Health, Charles Perkins Centre Nepean, The University of Sydney, Sydney, NSW, Australia.
² Department of Research Operations, Nepean Hospital, Sydney, NSW, Australia; Professorial Unit, The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.
³ Department of Cardiology, Nepean Hospital, Sydney, NSW, Australia; Department of Academic Medicine, Sydney Medical School Nepean, Faculty of Medicine and Health, Charles Perkins Centre Nepean, The University of Sydney, Sydney, NSW, Australia. Electronic address: Kazuaki.Negishi@sydney.edu.au.

PMID: 38184425
DOI: 10.1016/j.hlc.2023.11.004

Abstract

Background: The benefits in survivorship gained with anthracycline (ANT)-based chemotherapies for breast cancer are unfortunately mitigated for some patients by irreversible cardiotoxicity. Randomised controlled trials (RCTs) have explored multiple cardioprotection options, however, it remains unclear which drug is most effective in preserving left ventricular ejection fraction (LVEF). This study aimed to perform a systematic review and network meta-analysis, using Bayesian and frequentist approaches, of RCTs evaluating cardioprotective agents.

Methods: Two authors searched four databases (CENTRAL, Cochrane Reviews, MEDLINE, SCOPUS), to find RCTs evaluating cardioprotective agents. Trial populations were limited to patients with breast cancer without prior ANT exposure. The primary outcome was mean LVEF change pre and post ANT dosing. Our primary analysis utilised a Bayesian approach, while our sensitivity analysis used frequentist methodology (Prospero registration number CRD42020199580).

Results: From 4,007 search results, we identified 12 RCTs, with their various trial arms considered separately-nine beta-blocker (BB), two angiotensin-converting enzyme inhibitor /angiotensin receptor blockers [(AA)+BB=AABB], one AA, one spironolactone, one statin-evaluating 1,126 patients (age 50.5 years). Bayesian network meta-analysis showed no difference in LVEF preservation between AA (1.3%, 95% credible interval [-0.20, 2.9]), BB (0.77, [-0.21, 1.8]), AABB (0.84 [-1.1, 2.8]), spironolactone (0.72, [-2.3, 3.7]) or statin (0.60, [-2.4, 3.6]) when compared against placebo. However, the frequentist analysis showed benefits from using AA (mean difference, 1.32% [0.32, 2.33]) and BB (mean difference, 0.76% [0.12, 1.4]).

Conclusions: There is insufficient evidence to support prophylactic cardioprotection to prevent EF reduction. However, frequentist analysis suggested that AA or BBs provide cardioprotection. Thus, for those already on other anti-hypertensives, switching to AA or BBs could be considered.

Keywords: Breast cancer; CTRCD; Cardioprotection; Cardiotoxicity; Network meta-analysis.

Publication types

Meta-Analysis
Systematic Review

MeSH terms

Anthracyclines* / adverse effects
Anthracyclines* / therapeutic use
Bayes Theorem*
Breast Neoplasms* / drug therapy
Cardiotoxicity* / etiology
Cardiotoxicity* / prevention & control
Female
Humans
Network Meta-Analysis
Randomized Controlled Trials as Topic*
Ventricular Function, Left / drug effects
Ventricular Function, Left / physiology

Substances

Anthracyclines