Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada.
Institute for Clinical Evaluative Sciences, Toronto, Canada.
Ann Oncol. 2017 Mar 1;28(3):628-633. doi: 10.1093/annonc/mdw671.
The relative efficacy of interventions for primary prevention of anthracycline-associated cardiotoxicity is unknown.
We conducted a systematic review of randomized controlled trials for primary prevention of anthracycline-associated cardiotoxicity in adult cancer patients. We used hierarchal outcome definitions in the following order of priority: (1) composite of heart failure or decline in left ventricular ejection fraction, (2) decline in ejection fraction, or (3) heart failure. Data were analyzed using a Bayesian network meta-analysis with random effects.
A total of 16 trials reported cardiotoxicity as a dichotomous outcome among 1918 patients, evaluating dexrazoxane, angiotensin antagonists, beta-blockers, combination angiotensin antagonists and beta-blockers, statins, Co-enzyme Q-10, prenylamine, and N-acetylcysteine. Compared with control, dexrazoxane reduced cardiotoxicity with a pooled odds ratio (OR) of 0.26 (95% credible interval [CrI] 0.11-0.74) and had the highest probability (33%) of being most effective. No other agent was demonstrably better than placebo. Angiotensin antagonists had an 84% probability of being most effective in a sensitivity analysis excluding one outlying study (OR 0.06 [95% CrI 0.01- 0.24]). When the outcome was restricted to heart failure, dexrazoxane was associated with an OR of 0.12 (95% CrI 0.06-0.23) relative to control and had 58% probability of being most effective, while angiotensin antagonists had an OR of 0.18 (95% CrI 0.05-0.55). Available data suggested that dexrazoxane and angiotensin antagonists did not affect malignancy response rate or risk of death.
Moderate quality data suggest that dexrazoxane, and low quality data suggest angiotensin antagonists, are likely to be effective for cardiotoxicity prevention.
用于预防蒽环类药物相关性心脏毒性的干预措施的相对疗效尚不清楚。
我们对成人癌症患者中预防蒽环类药物相关性心脏毒性的一级预防进行了系统评价。我们按照以下优先顺序使用分层结局定义：（1）心力衰竭或左心室射血分数下降的综合结果，（2）射血分数下降，或（3）心力衰竭。使用贝叶斯网络荟萃分析进行数据分析，并采用随机效应。
16 项试验共纳入 1918 例患者，报道了心脏毒性的二分类结局，评估了右雷佐生、血管紧张素拮抗剂、β-受体阻滞剂、血管紧张素拮抗剂和β-受体阻滞剂联合、他汀类药物、辅酶 Q-10、泛醇胺、N-乙酰半胱氨酸。与对照组相比，右雷佐生降低心脏毒性的合并优势比（OR）为 0.26（95%可信区间[CrI] 0.11-0.74），最有效概率最高（33%）。没有其他药物明显优于安慰剂。血管紧张素拮抗剂在排除一项异常研究的敏感性分析中，最有效的概率为 84%（OR 0.06[95% CrI 0.01-0.24]）。当结局仅限于心力衰竭时，与对照组相比，右雷佐生的 OR 为 0.12（95% CrI 0.06-0.23），最有效概率为 58%，而血管紧张素拮抗剂的 OR 为 0.18（95% CrI 0.05-0.55）。现有数据表明，右雷佐生和血管紧张素拮抗剂不会影响恶性肿瘤的反应率或死亡率。
中等质量的数据表明，右雷佐生可能有效预防心脏毒性，低质量的数据表明血管紧张素拮抗剂可能有效预防心脏毒性。
