Heart Failure Department, Heart Institute (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Instituto do Câncer do Estado de São Paulo-Universidade de São Paulo, São Paulo, Brazil.
J Am Coll Cardiol. 2018 May 22;71(20):2281-2290. doi: 10.1016/j.jacc.2018.02.049. Epub 2018 Mar 11.
Anthracycline (ANT) chemotherapy is associated with cardiotoxicity. Prevention with β-blockers remains controversial.
This prospective, randomized, double-blind, placebo-controlled study sought to evaluate the role of carvedilol in preventing ANT cardiotoxicity.
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) 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.
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).
In this largest clinical trial of β-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 Chemotherapy-Induced Cardiotoxicity [CECCY]; NCT01724450).
蒽环类（ANT）化疗与心脏毒性相关。β受体阻滞剂预防仍然存在争议。
本前瞻性、随机、双盲、安慰剂对照研究旨在评估卡维地洛在预防 ANT 心脏毒性中的作用。
作者将 200 例 HER2 阴性乳腺癌肿瘤状态和正常左心室射血分数（LVEF）的患者随机分为卡维地洛或安慰剂组，直至化疗完成。主要终点是预防 6 个月时 LVEF 降低≥10%。次要终点是卡维地洛对肌钙蛋白 I、B 型利钠肽和舒张功能障碍的影响。
卡维地洛组 14 例（14.5%）和安慰剂组 13 例（13.5%）患者发生主要终点（p=1.0）。两组间 LVEF 或 B 型利钠肽的变化无差异。卡维地洛组的肌钙蛋白 I 水平随时间变化存在显著差异，卡维地洛组水平较低（p=0.003）。此外，卡维地洛组舒张功能障碍发生率较低（p=0.039）。卡维地洛组在随访期间 LV 舒张末期直径的增加趋势不明显（44.1±3.64mm 至 45.2±3.2mm 与 44.9±3.6mm 至 46.4±4.0mm；p=0.057）。
在当代 ANT 剂量下使用β受体阻滞剂预防心脏毒性的最大临床试验中，作者发现 13.5%至 14.5%的心脏毒性发生率。在这种情况下，卡维地洛对早期 LVEF 降低的发生率没有影响。然而，卡维地洛的使用导致肌钙蛋白水平和舒张功能障碍显著降低。（卡维地洛预防化疗诱导的心脏毒性作用[CECCY]；NCT01724450）。
