Efficacy of beta-blockers in preventing anthracycline-induced cardiotoxicity: updated meta-analysis of randomized controlled trials
P Silva De Marco, G M M Machado, S A Arora, M A N Nakazone, M N M Machado, L N M Maia, C M P D C S Silva, A V S M MacedoAbstract
Introduction
Cancer therapy-related cardiac dysfunction (CTRCD) is a common complication of anthracycline-based treatment in oncological patients.(1-3) Beta-blockers have been tested as potential prophylactic therapy for anthracycline-induced cardiotoxicity(4,5), but its role in primary prevention remains unclear.
Purpose
The purpose of this study was to evaluate the impact of beta-blockers in primary prevention of CTRCD in patients receiving anthracycline-based oncologic therapy for any type of cancer.
Methods
PubMed, EMBASE, and Cochrane databases were searched for randomized controlled trials comparing beta-blockers to placebo in the primary prevention of CTRCD in cancer patients planned to receive anthracyclines and reported the outcomes of: incidence of CTRCD; final left ventricular ejection fraction (LVEF); and diastolic function impairment. Heterogeneity was assessed using I2 statistics, and a random-effects model was applied.
Results
Out of 911 database results, 13 randomized trials(6-17) and 1040 patients were included; of whom 519 (49.9%) received beta-blockers. Most of the studies evaluated carvedilol in female patients with breast cancer and low cardiovascular risk. The median follow-up ranged from 3 months to 10 years. When multiple intervention arms were available, only the isolated beta-blocker arm or the group with the highest beta-blocker dose was evaluated. CTRCD was defined in most studies as a LVEF decrease > 10% and/or a decline to a value < 50-55%. The incidence of CTRCD was significantly lower in the beta-blocker group (RR 0.38; 95% CI 0.17-0.84; p=0.02; I2=53%). Although final LVEF values were statistically higher in the beta-blocker arm (MD 2.5; 95% CI 0.67–4.32; p=0.01), substantial heterogeneity was observed (I2=84%). Regarding diastolic function, the E/A ratio showed no significant difference between groups (MD 0.03; p = 0.39).
Conclusion
These findings initially suggest a potential protective effect of beta-blockers against the development of CTRCD. However, the limited number of events, substantial between-study heterogeneity, and persistently preserved final LVEF values (>55%) warrant cautious interpretation of these findings.