PDF(Pubmed)
Abstract：
Anthracycline-induced cardiotoxicity has a variable incidence, and the development of left ventricular dysfunction is preceded by elevations in cardiac troponin concentrations. Beta-adrenergic receptor blocker and renin-angiotensin system inhibitor therapies have been associated with modest cardioprotective effects in unselected patients receiving anthracycline chemotherapy.
In a multicenter, prospective, randomized, open-label, blinded end-point trial, patients with breast cancer and non-Hodgkin lymphoma receiving anthracycline chemotherapy underwent serial high-sensitivity cardiac troponin testing and cardiac magnetic resonance imaging before and 6 months after anthracycline treatment. Patients at high risk of cardiotoxicity (cardiac troponin I concentrations in the upper tertile during chemotherapy) were randomized to standard care plus cardioprotection (combination carvedilol and candesartan therapy) or standard care alone. The primary outcome was adjusted change in left ventricular ejection fraction at 6 months. In low-risk nonrandomized patients with cardiac troponin I concentrations in the lower 2 tertiles, we hypothesized the absence of a 6-month change in left ventricular ejection fraction and tested for equivalence of ±2%.
Between October 2017 and June 2021, 175 patients (mean age, 53 years; 87% female; 71% with breast cancer) were recruited. Patients randomized to cardioprotection (n=29) or standard care (n=28) had left ventricular ejection fractions of 69.4±7.4% and 69.1±6.1% at baseline and 65.7±6.6% and 64.9±5.9% 6 months after completion of chemotherapy, respectively. After adjustment for age, pretreatment left ventricular ejection fraction, and planned anthracycline dose, the estimated mean difference in 6-month left ventricular ejection fraction between the cardioprotection and standard care groups was -0.37% (95% CI, -3.59% to 2.85%; P=0.82). In low-risk nonrandomized patients, baseline and 6-month left ventricular ejection fractions were 69.3±5.7% and 66.4±6.3%, respectively: estimated mean difference, 2.87% (95% CI, 1.63%-4.10%; P=0.92, not equivalent).
Combination candesartan and carvedilol therapy had no demonstrable cardioprotective effect in patients receiving anthracycline-based chemotherapy with high-risk on-treatment cardiac troponin I concentrations. Low-risk nonrandomized patients had similar declines in left ventricular ejection fraction, bringing into question the utility of routine cardiac troponin monitoring. Furthermore, the modest declines in left ventricular ejection fraction suggest that the value and clinical impact of early cardioprotection therapy need to be better defined in patients receiving high-dose anthracycline.
URL: https://doi.org; Unique identifier: 10.1186/ISRCTN24439460. URL: https://www.clinicaltrialsregister.eu/ctr-search/search; Unique identifier: 2017-000896-99.
In a multicenter, prospective, randomized, open-label, blinded end-point trial, patients with breast cancer and non-Hodgkin lymphoma receiving anthracycline chemotherapy underwent serial high-sensitivity cardiac troponin testing and cardiac magnetic resonance imaging before and 6 months after anthracycline treatment. Patients at high risk of cardiotoxicity (cardiac troponin I concentrations in the upper tertile during chemotherapy) were randomized to standard care plus cardioprotection (combination carvedilol and candesartan therapy) or standard care alone. The primary outcome was adjusted change in left ventricular ejection fraction at 6 months. In low-risk nonrandomized patients with cardiac troponin I concentrations in the lower 2 tertiles, we hypothesized the absence of a 6-month change in left ventricular ejection fraction and tested for equivalence of ±2%.
Between October 2017 and June 2021, 175 patients (mean age, 53 years; 87% female; 71% with breast cancer) were recruited. Patients randomized to cardioprotection (n=29) or standard care (n=28) had left ventricular ejection fractions of 69.4±7.4% and 69.1±6.1% at baseline and 65.7±6.6% and 64.9±5.9% 6 months after completion of chemotherapy, respectively. After adjustment for age, pretreatment left ventricular ejection fraction, and planned anthracycline dose, the estimated mean difference in 6-month left ventricular ejection fraction between the cardioprotection and standard care groups was -0.37% (95% CI, -3.59% to 2.85%; P=0.82). In low-risk nonrandomized patients, baseline and 6-month left ventricular ejection fractions were 69.3±5.7% and 66.4±6.3%, respectively: estimated mean difference, 2.87% (95% CI, 1.63%-4.10%; P=0.92, not equivalent).
Combination candesartan and carvedilol therapy had no demonstrable cardioprotective effect in patients receiving anthracycline-based chemotherapy with high-risk on-treatment cardiac troponin I concentrations. Low-risk nonrandomized patients had similar declines in left ventricular ejection fraction, bringing into question the utility of routine cardiac troponin monitoring. Furthermore, the modest declines in left ventricular ejection fraction suggest that the value and clinical impact of early cardioprotection therapy need to be better defined in patients receiving high-dose anthracycline.
URL: https://doi.org; Unique identifier: 10.1186/ISRCTN24439460. URL: https://www.clinicaltrialsregister.eu/ctr-search/search; Unique identifier: 2017-000896-99.
摘要：
背景：蒽环类药物诱导的心脏毒性具有可变的发生率，左心室功能障碍的发展是由心肌肌钙蛋白浓度升高引起的。β-肾上腺素能受体阻滞剂和肾素-血管紧张素系统抑制剂治疗与未选择的蒽环类化疗患者的适度心脏保护作用相关。
方法：在多中心中，prospective,随机化，开放标签，盲法终点试验,接受蒽环类化疗的乳腺癌和非霍奇金淋巴瘤患者在蒽环类药物治疗前和治疗后6个月接受了系列高敏心肌肌钙蛋白检测和心脏磁共振成像.具有心脏毒性高风险（化疗期间上三位数的心肌肌钙蛋白I浓度）的患者被随机分为标准治疗加心脏保护（卡维地洛和坎地沙坦联合治疗）或仅接受标准治疗。主要结果为6个月时左心室射血分数的调整变化。在低风险的非随机患者中，心肌肌钙蛋白I浓度在较低的2三分位数，我们假设左心室射血分数6个月无变化,并进行了等效性检验±2%.
结果：2017年10月至2021年6月，175名患者（平均年龄，53岁；87％为女性；71％患有乳腺癌）被招募。随机接受心脏保护（n=29）或标准治疗（n=28）的患者在基线时的左心室射血分数分别为69.4±7.4％和69.1±6.1％，在完成后6个月化疗，分别为65.7±6.6％和64.9±5.9％。分别。调整后的年龄，预处理左心室射血分数,和计划的蒽环类药物剂量,心脏保护组和标准治疗组6个月左心室射血分数的估计平均差异为-0.37%(95%CI,-3.59%~2.85%;P=0.82).在低风险非随机患者中，基线和6个月左心室射血分数分别为69.3±5.7％和66.4±6.3％，分别为：估计平均差，2.87%（95%CI，1.63%-4.10%；P=0.92，不等值）。
结论：坎地沙坦和卡维地洛联合治疗对接受蒽环类化疗的患者没有明显的心脏保护作用，且治疗过程中心肌肌钙蛋白I浓度高。低危非随机患者左心室射血分数下降相似，质疑常规心肌肌钙蛋白监测的实用性。此外，左心室射血分数的适度下降表明,在接受大剂量蒽环类药物的患者中,需要更好地界定早期心脏保护治疗的价值和临床影响.
背景：URL：https://doi.org/10.1186/ISRCTN24439460；唯一标识符，ISRCTN24439460。URL：https://www.临床试验登记。eu/ctr-search/search?query=2017-000896-99;唯一标识符:EudraCT2017-000896-99。
方法：在多中心中，prospective,随机化，开放标签，盲法终点试验,接受蒽环类化疗的乳腺癌和非霍奇金淋巴瘤患者在蒽环类药物治疗前和治疗后6个月接受了系列高敏心肌肌钙蛋白检测和心脏磁共振成像.具有心脏毒性高风险（化疗期间上三位数的心肌肌钙蛋白I浓度）的患者被随机分为标准治疗加心脏保护（卡维地洛和坎地沙坦联合治疗）或仅接受标准治疗。主要结果为6个月时左心室射血分数的调整变化。在低风险的非随机患者中，心肌肌钙蛋白I浓度在较低的2三分位数，我们假设左心室射血分数6个月无变化,并进行了等效性检验±2%.
结果：2017年10月至2021年6月，175名患者（平均年龄，53岁；87％为女性；71％患有乳腺癌）被招募。随机接受心脏保护（n=29）或标准治疗（n=28）的患者在基线时的左心室射血分数分别为69.4±7.4％和69.1±6.1％，在完成后6个月化疗，分别为65.7±6.6％和64.9±5.9％。分别。调整后的年龄，预处理左心室射血分数,和计划的蒽环类药物剂量,心脏保护组和标准治疗组6个月左心室射血分数的估计平均差异为-0.37%(95%CI,-3.59%~2.85%;P=0.82).在低风险非随机患者中，基线和6个月左心室射血分数分别为69.3±5.7％和66.4±6.3％，分别为：估计平均差，2.87%（95%CI，1.63%-4.10%；P=0.92，不等值）。
结论：坎地沙坦和卡维地洛联合治疗对接受蒽环类化疗的患者没有明显的心脏保护作用，且治疗过程中心肌肌钙蛋白I浓度高。低危非随机患者左心室射血分数下降相似，质疑常规心肌肌钙蛋白监测的实用性。此外，左心室射血分数的适度下降表明,在接受大剂量蒽环类药物的患者中,需要更好地界定早期心脏保护治疗的价值和临床影响.
背景：URL：https://doi.org/10.1186/ISRCTN24439460；唯一标识符，ISRCTN24439460。URL：https://www.临床试验登记。eu/ctr-search/search?query=2017-000896-99;唯一标识符:EudraCT2017-000896-99。
