Efficacy of Carvedilol in Preventing Anthracycline-induced Cardiotoxicity: A Meta-analysis of Randomized Controlled Trials

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      Cancer Therapeutics Related Cardiac Dysfunction (CTRCD) is a common sequelae following treatment with anthracyclines. The non-selective beta-blocker, carvedilol, has shown potential benefit as primary prophylaxis in the prevention of CTRCD through its chronotropic and antioxidant properties. In this study, we aimed to assess the efficacy of carvedilol versus placebo in preventing CTRCD.


      Electronic databases were searched for randomized controlled trials which used carvedilol for patients who will undergo anthracycline-based chemotherapeutic regimen. Three independent reviewers assessed the quality of the eight studies based on the Cochrane Handbook for Systematic Reviews of Interventions prior to inclusion in the study. Data extracted were analyzed using Revman Version 5.3. Tests for heterogeneity was performed using the chi-square test.


      Eight randomized controlled trials with a total of 785 patients comparing carvedilol to placebo were assessed to be of good quality with low to moderate risk of bias. Results showed that patients on carvedilol had significantly higher post-treatment Left Ventricular Ejection Fraction (LVEF) (mean difference: 1.67, 95% CI: 0.89 to 2.44; p<0.01), with no dose response trend noted for the 12.5 mg dose (RR: 0.87, 95% CI: 0.43-1.73, p: 0.69) and 25 mg dose (RR: 0.85, 95% CI: 0.27-2.64, p: 0.77) compared to placebo. Patients on carvedilol had lower post-treatment end-systolic LV diameter (mean difference: -1.32, 95% CI: -2.36 to -0.28; p: 0.01), and lower end-diastolic LV diameter amongst those on higher doses (mean difference: -2.62, 95% CI: -4.66 to -0.58; p: 0.01). However, there was no statistically significant mortality difference between carvedilol and placebo (RR: 0.77, 95% CI: 0.40-1.50, p: 0.45).


      Our results demonstrated that carvedilol was able to prevent post-treatment reduction of LVEF and the attenuation of chamber enlargement amongst patients who underwent anthracycline-based chemotherapy. However, it had no effect on long-term mortality.
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