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

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.

Graphical abstract

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses Diagram for Study Selection Stepwise process from initial study identification, screening, determination of eligibility, and final study inclusion. Fifteen unique publications evaluating 17 therapeutic comparisons were selected. ICTRP = International Clinical Trials Registry Platform.

Figure 2

Treatment Effects on Changes in LVEF Pooled effects of neurohormonal therapies versus placebo on changes in LVEF from baseline to follow-up. Data are presented here as pooled weighted mean differences. LVEF = left ventricular ejection fraction; MRI = magnetic resonance imaging.

Central Illustration

Are Neurohormonal Therapies Beneficial in Preventing Cardiotoxicity in Patients Receiving Chemotherapy? In this updated meta-analysis of 17 studies enrolling patients receiving chemotherapy, randomization to neurohormonal therapy compared with placebo resulted in higher LVEF on follow-up with a small but statistically significant treatment effect. Small sample sizes, publication bias, and significant heterogeneity all limit clinical interpretability of these findings. Future trials of cardioprotective strategies adequately powered to detect clinical outcomes are needed. CI = confidential interval; HF = heart failure; LVEF = left ventricular ejection fraction.