Zhan T, Daniyal M, Li J, Mao Y
Hunan University of Chinese Medicine, 300 Xueshi Rd., Yuelu District, 410208, Changsha, Hunan, China.
Department of Integrated TCM and Western Medicine, The First Hospital of Changsha, 410005, Changsha, Hunan, China.
Herz. 2020 Dec;45(Suppl 1):1-14. doi: 10.1007/s00059-018-4779-y. Epub 2019 Jan 17.
Clinical or subclinical cardiotoxicity is a concern for cancer patients receiving anthracycline-based chemotherapy. Carvedilol is promising for preventing anthracycline-induced cardiotoxicity (AIC). This review appraised the preventive effects of carvedilol against AIC based on randomized controlled trials (RCTs).
The Cochrane Collaboration Central Register of Controlled Trials, PubMed, and Embase databases were searched from inception to March 27, 2018. RCTs using carvedilol for the prevention of AIC were selected. Risk of bias and methodological quality were assessed. Meta-analysis was conducted, when applicable, for the trial endpoints; otherwise the data were analyzed descriptively.
Nine RCTs comprising 717 patients were selected. The risk of bias was unclear and the methodological quality differed substantially. Data pooling of five eligible studies indicated no decreased mortality in patients receiving carvedilol (risk difference = -0.02, 95% CI: -0.07-0.04, p = 0.57, I = 44%). The impact on the incidence of left ventricular systolic dysfunction (LVSD) was inconsistently reported but meta-analysis was not applicable due to discordant LVSD definitions. Data pooling of eight studies and a subgroup analysis indicated a higher left ventricular ejection fraction (LVEF) with substantial heterogeneity in the carvedilol group (mean difference [MD] = 5.23, 95% CI: 2.20-8.27, p = 0.0007, I = 95%, and MD = 4.65, 95% CI: 0.67-8.64, p = 0.02, I = 90%, respectively). Further analysis of echocardiographic parameters and biomarkers showed weak evidence of improvement in diastolic function and troponin I level by carvedilol administration.
Preventive use of carvedilol in patients undergoing anthracycline-based chemotherapy may be associated with a reduced incidence of LVSD, higher LVEF value, better diastolic function, and lower troponin I level. RCTs with larger sample size and longer follow-up are needed to verify these findings.
临床或亚临床心脏毒性是接受蒽环类化疗的癌症患者所关注的问题。卡维地洛有望预防蒽环类药物引起的心脏毒性（AIC）。本综述基于随机对照试验（RCT）评估了卡维地洛对AIC的预防作用。
检索Cochrane协作网对照试验中央注册库、PubMed和Embase数据库，检索时间从数据库建库至2018年3月27日。选取使用卡维地洛预防AIC的RCT。评估偏倚风险和方法学质量。适当时对试验终点进行荟萃分析；否则对数据进行描述性分析。
选取了9项包含717例患者的RCT。偏倚风险不明确，方法学质量差异很大。5项符合条件的研究的数据合并表明，接受卡维地洛治疗的患者死亡率没有降低（风险差异=-0.02，95%CI：-0.07-0.04，p=0.57，I=44%）。对左心室收缩功能障碍（LVSD）发生率的影响报道不一致，但由于LVSD定义不一致，无法进行荟萃分析。8项研究的数据合并和亚组分析表明，卡维地洛组的左心室射血分数（LVEF）较高，存在较大异质性（平均差异[MD]=5.23，95%CI：2.20-8.27，p=0.0007，I=95%；MD=4.65，95%CI：0.67-8.64，p=0.02，I=90%）。对超声心动图参数和生物标志物的进一步分析显示，有较弱的证据表明卡维地洛给药可改善舒张功能和肌钙蛋白I水平。
在接受蒽环类化疗的患者中预防性使用卡维地洛可能与LVSD发生率降低、LVEF值升高、舒张功能改善和肌钙蛋白I水平降低有关。需要样本量更大、随访时间更长的RCT来验证这些发现。
