BBs, ACEI/ARBs to Prevent LV Dysfunction Due to Breast Cancer Drugs

Quick Takes

  • This is a meta-analysis of nine randomized controlled trials (n = 1,362). Three studies examined the preventive effect of heart failure treatments with trastuzumab and six with anthracycline treatments. The outcome was mean difference in LVEF at follow-up time.
  • In the primary analysis, ACEI/ARB therapy was not associated with improved LVEF irrespective of concomitant anthracycline or trastuzumab therapy. Beta-blocker therapy preserved LVEF significantly better compared with placebo.
  • Findings are supportive; however, the effect size was small and the studies had high risk of bias and moderate to high heterogeneity. Adequately powered clinical trials are needed prior to recommending systematic use of these therapies for prevention of cardiotoxicity.

Study Questions:

Are beta-blockers (BBs) and renin-angiotensin system blockers effective at preventing the decline in ejection fraction (EF) of women with breast cancer receiving trastuzumab, anthracyclines, or both?

Methods:

This study is a meta-analysis assessing the effect of BBs and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARBs) on left ventricular ejection fraction (LVEF) in patients treated with either trastuzumab, anthracyclines, or both. Meta-analyses estimated the pooled mean difference (MD) of LVEF at the follow-up time and associated 95% confidence intervals (CIs) between the group randomized to either BB or ACEI/ARB treatment versus a control group receiving placebo.

Results:

A total of nine randomized controlled trials (n = 1,362) were included in the analysis; three studies examined the preventive effect of heart failure treatments with trastuzumab and six with anthracycline treatments. Sample size varied from 45 to 469 patients. Two thirds of studies had high risk of bias and moderate to high heterogeneity. All patients were women. Mean age varied from 40.8 to 53.6 years. The baseline LVEF means varied between 59.5% and 66.0%. ACEI/ARB therapy irrespective of concomitant anthracycline or trastuzumab therapy was not significantly associated with improved LVEF compared to placebo (MD, 1.5; 95% CI, –0.6 to 3.7; p = 0.11; I2 = 52%). In contrast, BB therapy preserved LVEF significantly better compared with placebo (MD, 2.4; 95% CI, 0.3–4.5; p = 0.033; I2 = 82%). Both ACEI/ARBs and BBs were associated with preservation of LVEF compared to placebo in recipients of trastuzumab alone (MD, 2.3; 95% CI, 0.0–4.6; p = 0.047; I2 = 72%), but not anthracycline alone (MD, 1.9; 95% CI, –0.5 to 4.2; p = 0.096; I2 = 77%). Whether LVEF was a primary outcome or not did not influence the MD (p = 0.65), nor did the imaging modality.

Conclusions:

This meta-analysis suggests BBs and ACEI/ARBs may be effective in preventing decline in LVEF in women with breast cancer undergoing treatment with trastuzumab and/or anthracyclines.

Perspective:

Studies evaluating the effectiveness of BBs, ACEI/ARBs, and other therapies in preventing cardiotoxicity have been plagued by small sample sizes, low event rate, and great heterogeneity of patients and exposures, leading to overall low power and inconclusive findings. This meta-analysis combines these studies to suggest some positive impact for these medications, albeit the effect size is very small (difference in EF of 2%), and hard outcomes such as incident heart failure are not assessed. The risk of cardiotoxicity (age, diabetes mellitus, and others) is also not accounted for in this analysis. Overall, this meta-analysis is encouraging but does not impact current care. The effectiveness of these therapies as a preventive measure for cardiotoxicity needs to be validated in adequately powered clinical trials prior to considering recommending their use systematically.

Clinical Topics: Cardio-Oncology, Cardiovascular Care Team, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure

Keywords: Adrenergic beta-Antagonists, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Anthracyclines, Breast Neoplasms, Cardiotoxicity, Heart Failure, Renin-Angiotensin System, Secondary Prevention, Stroke Volume, Trastuzumab, Ventricular Dysfunction, Left, Ventricular Function, Left


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