Editorial commenton ‘A novel approach indirectly comparing benefit: risk across oral antithrombotic therapies inpatients with atrial fibrillation’.Are the evidences of current dose-adjusted anticoagulationwith warfarin stroke prevention for patients with
Editorial commenton ‘A novel approach indirectly comparing benefit: risk across oral antithrombotic therapies inpatients with atrial fibrillation’.Are the evidences of current dose-adjusted anticoagulationwith warfarin stroke prevention for patients with
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编辑评论“一种间接比较房颤患者口服抗血栓治疗获益的新方法：风险”。当前剂量调整抗凝与华法林卒中预防的证据是
DOI：
10.1093/ehjcvp/pvu017
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
S.
中科院分区：
文献类型：
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作者：
Goto;S. & Goto;S.
Dogliotti等人。使用已发表试验的荟萃分析来评估非维生素K拮抗剂口服抗凝剂[新型口服抗凝剂(NOAC)]的风险和益处，并得出结论，NOAC应该是首选的。在一级和二级预防环境中，新型口服抗凝剂用于房颤(AF)患者以预防中风。1、2由于房颤被报道为卒中的独立危险因素，抗血栓治疗在不同地区得到了实践指南的推荐。1、2之前发表的随机临床试验的荟萃分析显示，与安慰剂相比，抗凝治疗将房颤患者中风的风险降低了%。3尽管有这些证据证明抗凝治疗的疗效如此之高，但抗凝治疗并未得到广泛应用。这主要是因为担心出血风险增加，这在临床试验和现实世界的患者中表现出来，与具有严格的纳入和排除标准的临床试验患者相比，这些患者具有更多的复杂性(图1)。在NOAC开发之前，维生素K拮抗剂，如华法林，是许多国家临床上唯一可用的口服抗凝剂。因此，与前十年的安慰剂相比，抗凝的效果意味着华法林4-7对安慰剂的预防作用。目前由Dogliotti等人发表的报告。研究表明，NOAC是预防非瓣膜性房颤患者卒中的首选。这项研究包含旧的随机对照试验(RCT)，其中包括安慰剂组。这是非常有价值的，因为涉及房颤设置中NOAC的随机对照试验不包括安慰剂。由于在之前的试验中，华法林在有中风风险的房颤患者中显示出比安慰剂更好的疗效，因此在当代试验中加入安慰剂被认为是不道德的。有人可能会争辩说，在临床试验中招募的患者过于纯粹地被挑选出来，不能代表中风风险的房颤患者的全部谱系。我们必须小心地让我们的眼睛睁开眼睛，看看临床试验和他们的荟萃分析与现实世界中的真相之间的潜在差异，这些差异要复杂得多。因此，即使有一项涉及大量患者的分析作为荟萃分析，临床试验之外的患者样本的外部验证也是必要的。值得注意的是，所有主要的NOAC试验都比较了与以INR2-3为靶点的华法林的有效性和安全性(除了小样本大小的J-Rocket AF，70岁以上患者的目标INR为1.6-2.6)。选择4-8剂量的目标INR为2-3的华法林作为“假设性护理标准”，与NOAC进行比较，因为它们反映了目前临床指南推荐的华法林治疗。1、2虽然这一建议是基于证据的，但以前进行的比较抗凝和安慰剂9-14的试验大多是开放标签的(只有两个是双盲的)11、12，其中大多数过早停止。9-13在一级预防环境下的个人试验中，没有一项统计能力表明华法林治疗对有中风风险的房颤患者的存活率有好处。此外，
Dogliotti et al. evaluated the risk and benefit of non-vitamin K antagonistic oral anticoagulants [new oral anticoagulants (NOACs)] using a meta-analysis of published trials and have concluded that NOACs should be preferred. New oral anticoagulants are used in atrial fibrillation (AF) patients to prevent strokes in the primary and secondary prevention settings. 1, 2 Since AF are reported to be an independent risk factor for strokes, antithrombotic therapies are recommended by practice guideline in various regions. 1, 2 Previously published meta-analysis of randomized clinical trials revealed that anticoagulation therapies reduce the risk of stroke in AF patients by 64% compared with placebo. 3 Despite these evidences proving such high efficacy, anticoagulation therapies are not used widely. This is mostly due to the fear of increased risk of bleeding, shown in clinical trials and real-world patients, who have more complexities, compared with clinical trial patients with strict inclusion and exclusion criteria (Figure 1). Before NOACs were developed, vitamin K antagonists such as warfarin were the only clinically available oral anticoagulants for many countries. Thus the efficacy of anticoagulation compared with placebo in previous decade meant the preventive effects of warfarin 4–7 against placebo. The current report published by Dogliotti et al. has shown that NOACs are the preferred choice for stroke prevention in patients with non-valvular AF. This study contains old randomized controlled trails (RCTs) that include placebo arm. This is of great value because the RCT involving NOACs in the atrial fibrillation settings does not include placebos. Since warfarin showed a benefit over placebo in the previous trials in AF patients at risk of stroke, it is considered unethical to include a placebo arm in contemporary trials. One still might argue that the patients recruited in clinical trials are too purely selected to represent the whole spectrum of AF patients at risk of stroke. We have to be careful to make our eyes open on the potential difference between what have been shown in clinical trials and their meta-analysis and the truth in the real world, that are more complex. Thus even with an analysis involving a huge number of patients as meta-analysis, external validation with patients sample outside the world of clinical trials are necessary. It is of note that all the major NOACs trials compare efficacy and safety with warfarin targeting the INR 2–3 (except for small sample sized J-ROCKET AF where target INR in patients older than 70 was 1.6–2.6). 4–8 Dose of warfarin with target INR 2–3 were selected as ‘hypothetical standard of care’to make comparison with NOACs because they reflect the current recommendation of warfarin treatment by practice guideline. 1, 2 Although this recommendation is evidence based, the trials comparing anticoagulation with placebo 9–14 conducted previously are mostly open-labelled (only two are double-blinded) 11, 12 and the majority of them were stopped prematurely. 9–13 None of the individual trials in the primary prevention settings had the statistical power to show the benefit on survival with warfarin therapy for patients with AF with stroke risk. Furthermore,