Silber Jeffrey H, Cnaan Avital, Clark Bernard J, Paridon Stephen M, Chin Alvin J, Rychik Jack, Hogarty Alexa N, Cohen Mitchell I, Barber Gerald, Rutkowski Monika, Kimball Thomas R, Delaat Cynthia, Steinherz Laurel J, Zhao Huaqing
Center for Outcomes Research, Children's Hospital of Philadelphia, 3535 Market St, Suite 1029, Philadelphia, PA 19104, USA.
J Clin Oncol. 2004 Mar 1;22(5):820-8. doi: 10.1200/JCO.2004.06.022.
To determine whether an angiotensin-converting enzyme (ACE) inhibitor, enalapril, prevents cardiac function deterioration (defined using maximal cardiac index [MCI] on exercise testing or increase in left ventricular end-systolic wall stress [LVESWS]) in long-term survivors of pediatric cancer.
This was a randomized, double-blind, controlled clinical trial comparing enalapril to placebo in 135 long-term survivors of pediatric cancer who had at least one cardiac abnormality identified at any time after anthracycline exposure.
There was no difference in the rate of change in MCI per year between enalapril and placebo groups (0.30 v 0.18 L/min/m(2); P =.55). However, during the first year of treatment, the rate of change in LVESWS was greater in the enalapril group than in the placebo group (-8.59 v 1.85 g/cm(2); P =.033) and this difference was maintained over the study period, resulting in a 9% reduction in estimated LVESWS by year 5 in the enalapril group. Six of seven patients removed from random assignment to treatment because of cardiac deterioration were initially treated with placebo (P =.11), and one has died as a result of heart failure. Side effects from enalapril included dizziness or hypotension (22% v 3% in the placebo group; P =.0003) and fatigue (10% v 0%; P =.013).
Enalapril treatment did not influence exercise performance, but did reduce LVESWS in the first year; this reduction was maintained over the study period. Any theoretical benefits of LVESWS reduction in this anthracycline-exposed population must be weighed against potential side effects from ACE inhibitors when making treatment decisions.
确定血管紧张素转换酶（ACE）抑制剂依那普利是否能预防儿童癌症长期幸存者的心功能恶化（通过运动试验中的最大心指数[MCI]或左心室收缩末期壁应力[LVESWS]增加来定义）。
这是一项随机、双盲、对照临床试验，在135名儿童癌症长期幸存者中比较依那普利与安慰剂，这些幸存者在蒽环类药物暴露后的任何时间至少发现有一项心脏异常。
依那普利组和安慰剂组每年MCI的变化率无差异（0.30对0.18 L/分钟/平方米；P = 0.55）。然而，在治疗的第一年，依那普利组LVESWS的变化率高于安慰剂组（-8.59对1.85 g/cm²；P = 0.033），且在研究期间这种差异持续存在，导致依那普利组到第5年估计的LVESWS降低了9%。7名因心脏恶化而被取消随机分配治疗的患者中有6名最初接受了安慰剂治疗（P = 0.11），其中1名因心力衰竭死亡。依那普利的副作用包括头晕或低血压（安慰剂组为22%对3%；P = 0.0003）和疲劳（10%对0%；P = 0.013）。
依那普利治疗不影响运动表现，但在第一年确实降低了LVESWS；这种降低在研究期间持续存在。在做出治疗决策时，对于这个蒽环类药物暴露人群中LVESWS降低的任何理论益处，必须与ACE抑制剂的潜在副作用相权衡。
