Preventing LV Dysfunction Due to Chemotherapy in Patients With Breast Cancer

Beta-blockers were shown to attenuate the decline in left ventricular ejection fraction (LVEF) for patients with breast cancer being treated with trastuzumab, according to research findings published in the European Heart Journal.

The study found a similar, though statistically nonsignificant, result for patients with breast cancer treated with anthracyclines. Angiotensin receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEI) also resulted in a statistically nonsignificant higher LVEF compared with placebo for concomitant trastuzumab or anthracycline therapy.

In this meta-analysis of randomized controlled trials (RCTs), researchers evaluated the effects of beta-blockers, ACEI, and ARB therapies for trastuzumab- and anthracycline-associated cardiotoxicity in patients with breast cancer. Researchers included 9 RCTs from 2013 through 2019 involving 1362 patients in their analysis. All patients were women, and mean age between studies varied from 40.8 to 53.6 years. None of the patients had previous cardiovascular disease, and the duration of chemotherapy ranged between 63 and 365 days for all patients.

Beta-blocker therapy preserved LVEF significantly better in patients with breast cancer treated with trastuzumab or anthracyclines compared with placebo (mean difference [MD], 2.4; 95% CI, 0.3-4.5; P=.033; I² = 82%). ACEI/ARB therapy resulted in a nonsignificantly higher LVEF in patients with breast cancer treated with trastuzumab or anthracyclines compared with placebo (MD, 1.5; 95% CI, -0.6 to 3.7; P=.11; I² = 52%).

Researchers noted several limitations in their analysis. Of the 9 studies, 6 were assessed to have high risk of bias in randomization and blinding, and a lack of clear description of methods. Attrition bias was high in 4 of the studies. Researchers also cited the variety of supplementary breast cancer treatments before or after trastuzumab and anthracycline regimens as a limitation, and added that the optimal dose of beta-blockers and ACEI/ARBs remains unknown, as does the optimal combination of ACEI/ARBs and beta-blockers.

“[Beta-blockers] but not ACEI/ARBs were found to preserve LVEF significantly and more effectively than placebo in breast cancer patients receiving adjuvant trastuzumab and/or anthracyclines,” the study authors noted. “Despite heterogeneity in effect sizes, only positive associations between LVEF and the interventional drugs were found. Our results therefore may suggest prescription of either ACEI/ARBs or [beta-blockers] during trastuzumab and/or anthracycline therapy in patients undergoing breast cancer treatment.”

Disclosure: Some study author(s) declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Lewinter C, Nielsen TH, Edfors LR, et al. A systematic review and meta-analysis of beta-blockers and renin-angiotensin system inhibitors for preventing left ventricular dysfunction due to anthracyclines or trastuzumab in patients with breast cancer. Eur Heart J. Published online December 24, 2021. doi:10.1093/eurheartj/ehab843