Preventive use of carvedilol for anthracycline-induced cardiotoxicity: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND

Clinical or subclinical cardiotoxicity is a concern for cancer patients receiving anthracycline-based chemotherapy. Carvedilol is promising for preventing anthracycline-induced cardiotoxicity (AIC). This review appraised the preventive effects of carvedilol against AIC based on randomized controlled trials (RCTs).

METHODS

The Cochrane Collaboration Central Register of Controlled Trials, PubMed, and Embase databases were searched from inception to March 27, 2018. RCTs using carvedilol for the prevention of AIC were selected. Risk of bias and methodological quality were assessed. Meta-analysis was conducted, when applicable, for the trial endpoints; otherwise the data were analyzed descriptively.

RESULTS

Nine RCTs comprising 717 patients were selected. The risk of bias was unclear and the methodological quality differed substantially. Data pooling of five eligible studies indicated no decreased mortality in patients receiving carvedilol (risk difference = -0.02, 95% CI: -0.07-0.04, p = 0.57, I = 44%). The impact on the incidence of left ventricular systolic dysfunction (LVSD) was inconsistently reported but meta-analysis was not applicable due to discordant LVSD definitions. Data pooling of eight studies and a subgroup analysis indicated a higher left ventricular ejection fraction (LVEF) with substantial heterogeneity in the carvedilol group (mean difference [MD] = 5.23, 95% CI: 2.20-8.27, p = 0.0007, I = 95%, and MD = 4.65, 95% CI: 0.67-8.64, p = 0.02, I = 90%, respectively). Further analysis of echocardiographic parameters and biomarkers showed weak evidence of improvement in diastolic function and troponin I level by carvedilol administration.

CONCLUSION

Preventive use of carvedilol in patients undergoing anthracycline-based chemotherapy may be associated with a reduced incidence of LVSD, higher LVEF value, better diastolic function, and lower troponin I level. RCTs with larger sample size and longer follow-up are needed to verify these findings.