Risk of drug-induced liver injury with the new oral anticoagulants: systematic review and meta-analysis
Risk of drug-induced liver injury with the new oral anticoagulants: systematic review and meta-analysis
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DOI：
10.1136/heartjnl-2013-305288
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发表时间：
2014-04-01
期刊：
影响因子：
5.7
通讯作者：
Costa, Joao
中科院分区：
文献类型：
--
作者：
Caldeira, Daniel;Barra, Marcio;Costa, Joao
目的近年来，心血管药物引起严重药物性肝损伤（DILI）的风险已被提出安全警示。新型口服抗凝剂（NOAC）现已上市。然而，已经提出了关于其肝脏安全性的安全性问题。因此，我们的目的是评估NOAC肝脏相关safety.Methods系统回顾和荟萃分析的III期随机对照试验（RCT）。检索Medline和CENTRAL至2013年9月。还检索了综述和参考文献列表。两名评审员独立检索研究并检索数据估计值。主要结局为DILI（转氨酶升高> 3倍正常值上限（ULN），总胆红素> 2倍ULN）。将NOAC与任何对照组进行比较。结果共纳入29篇随机对照试验，平均随访时间16个月，共纳入152116例患者。所有RCT均被评定为偏倚风险较低。NOAC与DILI风险增加无关（RR 0.90，95% CI 0.72 - 1.13，I-2=0%）。单个NOAC（利伐沙班、阿哌沙班、达比加群、达瑞沙班、依度沙班）和不同对照组（维生素K拮抗剂、低分子量肝素（LMWH）和安慰剂）获得了相似的结果。NOAC治疗患者转氨酶升高（>3xULN）的风险较低，特别是与LMWH治疗患者相比（RR 0.71，95%CI 0.59至0.85; I-2=27%）。NOAC的意外保护作用可能是由于LMWH相关的肝毒性。
Objective In recent years, safety alerts have been made warning of the risk of serious drug-induced liver injury (DILI) caused by cardiovascular drugs. The new oral anticoagulants (NOACs) have now reached the market. However, safety concerns have been raised about their hepatic safety. Therefore we aimed to evaluate NOAC liver-related safety.Methods Systematic review and meta-analysis of phase III randomised controlled trials (RCTs). Medline and CENTRAL were searched to September 2013. Reviews and reference lists were also searched. Two reviewers independently searched for studies and retrieved data estimates. Primary outcome was DILI (transaminases elevations >3x upper limit of normal (ULN) with total bilirubin >2x ULN). NOACs were compared against any control group. Random-effects meta-analysis was performed, and pooled estimates were expressed as relative risk (RR) and 95% CI heterogeneity was evaluated with I-2 test.Results Twenty-nine RCTs evaluating 152116 patients (mean follow-up of 16months) were included. All RCTs were rated as having low risk of bias. NOAC were not associated with an increased risk of DILI (RR 0.90, 95% CI 0.72 to 1.13, I-2=0%). Similar results were obtained for individual NOAC (rivaroxaban, apixaban, dabigatran, darexaban, edoxaban) and considering the different control groups (vitamin K antagonists, low molecular weight heparin (LMWH) and placebo). The risk of transaminases elevations (>3xULN) was lower among NOAC-treated patients, in particular in comparison with LMWH-treated patients (RR 0.71, 95% CI 0.59 to 0.85; I-2=27%)Conclusions NOACs are not associated with an increased risk of DILI. The unexpected protective' effect of NOAC is probably due to LMWH-associated hepatotoxicity.