Oral anticoagulants for primary prevention, treatment and secondary prevention of venous thromboembolic disease, and for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis and cost-effectiveness analysis
Oral anticoagulants for primary prevention, treatment and secondary prevention of venous thromboembolic disease, and for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis and cost-effectiveness analysis
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DOI：
10.3310/hta21090
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发表时间：
2017-03-01
影响因子：
3.6
通讯作者：
Hingorani, Aroon D.
中科院分区：
文献类型：
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作者：
Sterne, Jonathan A. C.;Bodalia, Pritesh N.;Hingorani, Aroon D.
背景：华法令可有效预防心房颤动(房颤)患者的卒中，但在临床护理中抗凝作用未得到充分利用。低分子肝素(LMWH)可以降低住院期间静脉血栓栓塞症的风险：华法林是治疗和二级预防静脉血栓栓塞症(VTE)最常用的抗凝剂。华法林相关出血是因药物不良反应而住院的主要原因。华法林很便宜，但治疗监测增加了治疗成本。新型口服抗凝剂(NOAC)具有比华法令更快的起效和止血作用，以及更可预测的剂量要求。目的：确定预防房颤和VTE一级预防、治疗和二级预防的最佳口服抗凝剂/S。设计：随机对照试验的四项系统评价、网络荟萃分析(NMA)和成本-效果分析(CEAS)。地点：医院(房颤一级预防和急性治疗)和初级保健/抗凝诊所(房颤和二级预防)。参与者：符合华法令抗凝治疗条件的患者(房颤卒中预防，干预措施：NOACs、华法林和低MWH与其他干预措施(抗血小板治疗、安慰剂)一起在证据网络中进行评估。主要观察指标：有效率卒中、症状性VTE、症状性深静脉血栓形成和症状性肺栓塞。安全性大出血、临床相关出血和颅内出血。资料来源：Medline和PREMEDLINE in-Process及其他非索引引文，EMBASE和Cochrane图书馆，已发表NMA和试验注册的参考列表。我们检索了MEDLINE和PREMEDLINE in-Process及其他非索引引文、EMBASE和Cochrane图书馆。AF中的卒中预防回顾检索于2014年3月12日运行，并于2014年9月15日更新，涵盖2010年至2014年9月。对VTE中的三篇综述的检索于2014年3月19日进行，更新于2014年9月15日，涵盖2008年至2014年9月。综述方法：两名评价者筛选搜索结果，提取和核对数据，并评估偏倚风险。对于每个结果，我们进行了标准的荟萃分析和NMA。结果：apixaban(美国百时美施贵宝Eiquis((R))；美国辉瑞(Pfizer))[5 mg bd(每天两次)]被评为预防房颤卒中的最佳干预措施之一，并具有最高的预期净收益。依多沙班(日本第一三共Lixiana((R)[60毫克服药(每天一次)]在大出血和各种原因死亡率方面排名第二。无论是临床疗效分析还是CEA，都没有提供强有力的证据表明NOAC应该取代术后LMWH用于VTE的一级预防。对于VTE的急性治疗和二级预防，我们发现几乎没有证据表明NOAC比华法林具有疗效优势，但一些NOAC的出血并发症风险低于华法林。对于>；[原文如此]5000的支付意愿阈值，apixaban(5 Mg Bd)对于VTE的急性治疗具有最高的预期净收益。阿司匹林或非药物治疗可能是VTE二级预防的最具成本效益的干预措施：我们的结果表明，对于这一指征，开NOAC或华法林并不划算。结论：NOAC在房颤患者中比华法林更具优势，但我们没有发现强有力的证据表明它们应该在VTE的一级预防、治疗或二级预防中取代华法林或低分子肝素。
Background: Warfarin is effective for stroke prevention in atrial fibrillation (AF), but anticoagulation is underused in clinical care. The risk of venous thromboembolic disease during hospitalisation can be reduced by low-molecular-weight heparin (LMWH): warfarin is the most frequently prescribed anticoagulant for treatment and secondary prevention of venous thromboembolism (VTE). Warfarin-related bleeding is a major reason for hospitalisation for adverse drug effects. Warfarin is cheap but therapeutic monitoring increases treatment costs. Novel oral anticoagulants (NOACs) have more rapid onset and offset of action than warfarin, and more predictable dosing requirements.Objective: To determine the best oral anticoagulant/s for prevention of stroke in AF and for primary prevention, treatment and secondary prevention of VTE.Design: Four systematic reviews, network meta-analyses (NMAs) and cost-effectiveness analyses (CEAs) of randomised controlled trials.Setting: Hospital (VTE primary prevention and acute treatment) and primary care/anticoagulation clinics (AF and VTE secondary prevention).Participants: Patients eligible for anticoagulation with warfarin (stroke prevention in AF, acute treatment or secondary prevention of VTE) or LMWH (primary prevention of VTE).Interventions: NOACs, warfarin and LMWH, together with other interventions (antiplatelet therapy, placebo) evaluated in the evidence network.Main outcome measures: Efficacy Stroke, symptomatic VTE, symptomatic deep-vein thrombosis and symptomatic pulmonary embolism. Safety Major bleeding, clinically relevant bleeding and intracranial haemorrhage. We also considered myocardial infarction and all-cause mortality and evaluated cost-effectiveness.Data sources: MEDLINE and PREMEDLINE In-Process & Other Non-Indexed Citations, EMBASE and The Cochrane Library, reference lists of published NMAs and trial registries. We searched MEDLINE and PREMEDLINE In-Process & Other Non-Indexed Citations, EMBASE and The Cochrane Library. The stroke prevention in AF review search was run on the 12 March 2014 and updated on 15 September 2014, and covered the period 2010 to September 2014. The search for the three reviews in VTE was run on the 19 March 2014, updated on 15 September 2014, and covered the period 2008 to September 2014.Review methods: Two reviewers screened search results, extracted and checked data, and assessed risk of bias. For each outcome we conducted standard meta-analysis and NMA. We evaluated cost-effectiveness using discrete-time Markov models.Results: Apixaban (Eliquis((R)), Bristol-Myers Squibb, USA; Pfizer, USA) [5 mg bd (twice daily)] was ranked as among the best interventions for stroke prevention in AF, and had the highest expected net benefit. Edoxaban (Lixiana((R)), Daiichi Sankyo, Japan) [60 mg od (once daily)] was ranked second for major bleeding and all-cause mortality. Neither the clinical effectiveness analysis nor the CEA provided strong evidence that NOACs should replace postoperative LMWH in primary prevention of VTE. For acute treatment and secondary prevention of VTE, we found little evidence that NOACs offer an efficacy advantage over warfarin, but the risk of bleeding complications was lower for some NOACs than for warfarin. For a willingness-to-pay threshold of > [SIC] 5000, apixaban (5 mg bd) had the highest expected net benefit for acute treatment of VTE. Aspirin or no pharmacotherapy were likely to be the most cost-effective interventions for secondary prevention of VTE: our results suggest that it is not cost-effective to prescribe NOACs or warfarin for this indication.Conclusions: NOACs have advantages over warfarin in patients with AF, but we found no strong evidence that they should replace warfarin or LMWH in primary prevention, treatment or secondary prevention of VTE.