Carvedilol for Prevention of Chemotherapy-Related Cardiotoxicity

BACKGROUND Anthracycline (ANT) chemotherapy is associated with cardiotoxicity. Prevention with beta-blockers remains controversial. OBJECTIVES This prospective, randomized, double-blind, placebo-controlled study sought to evaluate the role of carvedilol in preventing ANT cardiotoxicity. METHODS The authors randomized 200 patients with HER2-negative breast cancer tumor status and normal left ventricular ejection fraction (LVEF) referred for ANT (240 mg/m(2)) to receive carvedilol or placebo until chemotherapy completion. The primary endpoint was prevention of a >= 10% reduction in LVEF at 6 months. Secondary outcomes were effects of carvedilol on troponin I, B-type natriuretic peptide, and diastolic dysfunction. RESULTS Primary endpoint occurred in 14 patients (14.5%) in the carvedilol group and 13 patients (13.5%) in the placebo group (p = 1.0). No differences in changes of LVEF or B-type natriuretic peptide were noted between groups. A significant difference existed between groups in troponin I levels over time, with lower levels in the carvedilol group (p = 0.003). Additionally, a lower incidence of diastolic dysfunction was noted in the carvedilol group (p = 0.039). A nonsignificant trend toward a less-pronounced increase in LV end-diastolic diameter during the follow-up was noted in the carvedilol group (44.1 +/- 3.64 mm to 45.2 +/- 3.2 mm vs. 44.9 +/- 3.6 mm to 46.4 +/- 4.0 mm; p = 0.057). CONCLUSIONS In this largest clinical trial of beta-blockers for prevention of cardiotoxicity under contemporary ANT dosage, the authors noted a 13.5% to 14.5% incidence of cardiotoxicity. In this scenario, carvedilol had no impact on the incidence of early onset of LVEF reduction. However, the use of carvedilol resulted in a significant reduction in troponin levels and diastolic dysfunction.(Carvedilol Effect in Preventing Chemotherap-Induced Cardiotoxicity [CECCy] NCTO1724450)(C) 2018 by the American College of Cardiology Foundation.