Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Department of Cardiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Pediatr Blood Cancer. 2018 Nov;65(11):e27308. doi: 10.1002/pbc.27308. Epub 2018 Jul 15.
Several measures including drugs have been tried to reduce anthracycline cardiotoxicity. The lack of randomized trials prompted this study to assess the role of an angiotensin converting enzyme (ACE) inhibitor (enalapril) in anthracycline-induced cardiotoxicity in children with hematological malignancies.
A randomized, double-blind, placebo-controlled trial was conducted on 84 patients with leukemia (41) and lymphoma (43) who received anthracyclines (doxorubicin and/or daunorubicin) at cumulative dose ≥200 mg/m . The patients were randomized to receive either enalapril [group A (n = 44)] or placebo [group B (n = 40)] for 6 months. Left ventricular ejection fraction (LVEF) and cardiac biomarkers (cardiac troponin I [cTnI], probrain natriuretic peptide [proBNP], and creatine kinase MB [CK-MB]) were assessed at baseline and 6 months. The primary outcome was a measured decrease in LVEF (≥20%). Secondary outcome measures were changes in cardiac biomarkers and the development of heart failure or arrhythmias.
LVEF decreased in both groups at 6 months, more so in group B (62.25 ± 5.49 vs 56.15 ± 4.79, P < 0.001). A ≥20% decrease was seen in 3 patients in group B but none in group A (P = 0.21). Cardiac biomarkers increased more in group B at 6 months, and the increase was significant for proBNP (49.60 ± 35.97 vs 98.60 ± 54.24, P < 0.001) and cTnI (0.01 ± 0.00 vs 0.011 ± 0.003, P = 0.035) but not significant for CK-MB (1.08 ± 0.18 vs 1.21 ± 0.44, P = 0.079). In group A, 9.1% of the patients showed an increase in proBNP level ≥100 compared with 37.5% in group B (P < 0.001). No patient developed heart failure or arrhythmia.
Enalapril has a role in reducing cardiac toxicity after anthracycline administration.
已经尝试了几种措施，包括药物，以减少蒽环类药物的心脏毒性。由于缺乏随机试验，因此本研究旨在评估血管紧张素转换酶（ACE）抑制剂（依那普利）在接受蒽环类药物（阿霉素和/或柔红霉素）累积剂量≥200mg/m 的血液恶性肿瘤儿童中的蒽环类药物诱导的心脏毒性中的作用。
对 84 例接受蒽环类药物（阿霉素和/或柔红霉素）累积剂量≥200mg/m 的白血病（41 例）和淋巴瘤（43 例）患者进行了随机、双盲、安慰剂对照试验。患者被随机分为依那普利（A 组，n=44）或安慰剂（B 组，n=40）组，治疗 6 个月。在基线和 6 个月时评估左心室射血分数（LVEF）和心脏生物标志物（心肌肌钙蛋白 I [cTnI]、脑利钠肽前体 [proBNP]和肌酸激酶同工酶 MB [CK-MB]）。主要结局是 LVEF 下降（≥20%）。次要结局指标为心脏生物标志物的变化和心力衰竭或心律失常的发生。
两组患者在 6 个月时 LVEF 均下降，B 组下降更明显（62.25±5.49 比 56.15±4.79，P<0.001）。B 组有 3 例患者 LVEF 下降≥20%，而 A 组无患者下降（P=0.21）。B 组在 6 个月时心脏生物标志物升高更明显，proBNP 升高有统计学意义（49.60±35.97 比 98.60±54.24，P<0.001），cTnI 升高有统计学意义（0.01±0.00 比 0.011±0.003，P=0.035），但 CK-MB 升高无统计学意义（1.08±0.18 比 1.21±0.44，P=0.079）。A 组有 9.1%的患者 proBNP 水平升高≥100，而 B 组有 37.5%的患者升高（P<0.001）。没有患者发生心力衰竭或心律失常。
依那普利在减少蒽环类药物后心脏毒性方面有一定作用。
