Lamberts及同事在心肌梗死（MI）后或经皮冠状动脉介入治疗（PCI）后的心房颤动（AF）患者中，研究多重抗栓治疗方案的血栓形成和出血风险。纳入12 165例因MI住院或接受PCI的AF患者，并根据抗栓治疗方案评估MI/冠心病死亡、缺血性卒中和出血风险。1年内，分别有2255例（18.5%）、680例（5.6%）和756例（6.3%）患者发生MI或冠心病死亡、缺血性卒中和出血事件。相对于三联疗法（口服抗凝药物[OAC]+阿司匹林+氯吡格雷），OAC+氯吡格雷、OAC+阿司匹林或阿司匹林+氯吡格雷疗法未见冠状动脉事件复发风险增加，但阿司匹林+氯吡格雷导致缺血性卒中风险较高。与三联疗法相比，OAC+氯吡格雷的出血风险非显著性降低，阿司匹林+氯吡格雷则显著降低。作者总结，在临床实际情况中，对MI/ PCI后有多重抗栓治疗适应证的AF患者，OAC+氯吡格雷与三联疗法相比在获益和安全性结果方面相等或更好。
J Am Coll Cardiol. 2013;62(11):981-989.
特邀点评
Add-on Antiplatelet Therapy in Atrial Fibrillation Patients on Warfarin after Myocardial Infarction or Coronary Intervention.
比利时布鲁塞尔Brugmann大学医院 Safouris Apostolos
Adding one or two antiplatelet agents on top of oral anticoagulation (OAC) is the current standard of care for atrial fibrillation (AF) patients post myocardial infarction (MI) or percutanous coronary intervention (PCI). The well-known excess bleeding risk of double or triple antithrombotic treatment is considered a rational trade-off for myocardial re-infarction or stent thrombosis in the acute phase but there is accumulating evidence that prolonged treatment comes with serious bleeding complications that could diminish any potential (and still unproven) benefit. Current guidelines from the European Society of Cardiology Working Group on Thrombosis for the antithrombotic treatment post PCI of non-valvular AF patients necessitating anticoagulation advocate triple antithrombotic treatment for 2 weeks up to 6 months depending on stent type (drug eluting or not)， bleeding risk and the whether the intervention was elective or performed in an acute setting. These recommendations are only based on nonrandomized studies but data is growing that prolonged triple antithrombotic treatment could be deleterious. In the September issue of the Journal of the American College of Cardiology， Lamberts et al. assessed the risk of thrombosis and bleeding of many antithrombotic regimens in AF patients post MI or PCI. The authors performed a retrospective analysis of the Danish National Patient Registry and identified more than 12，000 AF patients hospitalized for MI and/or undergoing PCI between 2001 and 2009. Aspirin， clopidogrel and OAC monotherapy， double antiplatelet therapy， double antithrombotic therapy (OAC plus aspirin or clopidogrel) and triple antithrombotic therapy (OAC plus clopidogrel plus aspirin) were evaluated for hemorrhagic or thrombotic complications at one year after initiation of therapy. The main finding was that there seems to be no benefice in adding aspirin to OAC plus clopidogrel. The authors concluded that triple antithrombotic therapy could be safely replaced by OAC and clopidogrel.
This study comes as a great contribution to the current controversy over the common clinical problem of medical management of AF patients needing antiplatelet therapy. This is the largest epidemiological study made on this issue， based on the medical registries of the entire Danish population. It is also a real-life patients study combining data from different centres and including all kind of patients regardless health insurance coverage or other confounders. What this paper tells us is that more drugs could mean less for AF patients， a statement already raised by another Scandinavian study published in 2013， the WOEST trial， an open-label， multicenter， randomised controlled study according to which adding aspirin on top of OAC plus clopidogrel post PCI in AF patients confers no thrombo-prophylaxis and carries an increased bleeding risk. The study by Lamberts et al. compared numerous antithrombotic regimens and found that the combination of OAC plus clopidogrel seems to present the best risk-benefit profile. Last but not least， the selection of antithrombotic treatment by the clinicians was not influenced by the predicted stroke risk as assessed by the CHADS2 score， a validated tool that has been in clinical practice since 2001. Such a seemingly random treatment of AF patients should alert clinicians. Adherence to the guidelines for thrombo-prophylaxis in AF patients remains an issue as demonstrated by Warlé-Van Herwaarden et al. in 2012， and is probably a cause of frequent and severe iatrogenic complications in the AF patient population.
Some limitations of the study should be noted. First of all， selection bias could not be excluded as triple antithrombotic therapy could be preferred for “healthier” patients with less medical co-morbidities. Secondly， no novel anticoagulants (NOACs) were studied， as observation terminated at 2009. NOACs are currently approved for non-valvular AF and their clinical use is growing but data is still scarce regarding the risk-benefit ratio when combined with antiplatelets. Thirdly， outcomes are only studied at one year after MI or PCI. It still remains unclear whether triple antithrombotic therapy should be used in the acute phase after MI or PCI (eg 2 weeks to 3 months). It could be asserted that an initial clinical benefit could be alleviated by an increased bleeding risk afterwards. This study would be much more significant if it could compare outcomes in patients receiving these antithrombotic regimens in 3 as well as in 12 months.
Despite the aforementioned limitations， this is an important contribution that helps physicians select an optimal antithrombotic therapy for AF patients post MI or PCI. In the absence of prospective studies that could provide high-quality data， clinicians should seriously revise the widely established clinical practice of prolonged triple antithrombotic therapy in AF patients post MI or PCI. If there is still a role for triple therapy， it should be limited in the acute phase， according to current guidelines. OAC and clopidogrel combination seems to be equally effective to triple antithrombotic therapy. However， as we entering the era of NOACs， OAC-based regimens could soon prove obsolete and research for combined therapies including the novel agents is urgently needed.
中文摘要
OAC基础上加一到两种抗血小板药物是当前AF患者MI后或PCI后的标准治疗手段。急性期双联或三联抗栓治疗的出血风险可与再发MI或支架血栓形成风险相权衡，然而，延长治疗可导致严重出血，可抵消任何可能获益。目前，ESC血栓工作组推荐对需抗凝治疗的非瓣膜性AF患者，PCI后抗栓治疗应根据支架类型（药物洗脱或裸支架）、出血风险和是否择期手术，考虑2周至6个月的三联疗法。这些推荐是基于非随机临床研究数据，但不断增加的新数据提示延长的三联抗栓治疗有害。Lambert等对2001～2009年丹麦全国患者注册数据进行回顾性分析，确定超过12 000例因MI和/或PCI住院的AF患者。在启动治疗1年后，评估阿司匹林、氯吡格雷和OAC单药治疗、双联抗血小板治疗、双联抗栓治疗和三联抗栓治疗的出血和血栓形成风险。研究结果提示，在OAC加氯吡格雷基础上，再加用阿司匹林似乎并无益处。作者提出三联疗法可以安全地被OAC加氯吡格雷替代。
目前，需抗血小板治疗的AF患者管理存在很大争议，该研究对此有重大贡献。这是关于这一问题的规模最大的流行病学研究，涵盖丹麦全部人口；同时也是一项真实临床实践研究，纳入多个中心有各种混杂因素的患者。研究结果告诉我们，对AF患者，更多药物并无意义。2013年发表的瑞典WOEST研究也提出相同结论。该项多中心随机对照、开放标签试验发现在OAC加氯吡格雷基础上加用阿司匹林，对PCI后AF患者的血栓形成无更多预防价值，而且增加出血风险。Lambert等的研究提示，OAC加氯吡格雷的风险获益平衡最佳
Lambert等的研究也存在局限性。不能排除选择偏倚，三联疗法可能更多用于“更健康”的患者。这项研究终止于2009年，因此尚未应用新型抗凝药物（NOAC）；仅研究MI或PCI后1年的结果。不清楚三联抗栓疗法是否应在急性期（2周到3个月）应用，起始的临床获益可能被随后的出血风险抵消。该研究如果能比较3个月时和12个月时的结果，意义将更大。
[下一页] [1] [2] [3]