Komócsi András, Vorobcsuk András, Kehl Dániel, Aradi Dániel
Department of Interventional Cardiology, Heart Institute, University of Pécs, Pécs, Hungary.
Arch Intern Med. 2012 Nov 12;172(20):1537-45. doi: 10.1001/archinternmed.2012.4026.
Despite receipt of dual antiplatelet therapy, patients after an acute coronary syndrome (ACS) remain at significant risk for thrombotic events. The role of orally activated Xa antagonist (anti-Xa) and direct thrombin inhibitors is debated in this setting. Our study objective was to evaluate the efficacy and safety of new-generation oral anticoagulant agents compared with placebo in patients receiving antiplatelet therapy after an ACS.
Electronic databases were searched to identify prospective randomized placebo-controlled clinical trials that evaluated the effects of anti-Xa or direct thrombin inhibitors in patients receiving antiplatelet therapy after an ACS. Efficacy measures included stent thrombosis, overall mortality, and a composite end point of major ischemic events, while thrombolysis in myocardial infarction-defined major bleeding events were used as a safety end point. The net clinical benefit was calculated as the sum of composite ischemic events and major bleeding events.
For the period January 1, 2000, through December 31, 2011, we identified 7 prospective randomized placebo-controlled clinical trials that met the study criteria, involving 31 286 patients. Based on the pooled results, the use of new-generation oral anticoagulant agents in patients receiving antiplatelet therapy after an ACS was associated with a dramatic increase in major bleeding events (odds ratio, 3.03; 95% CI, 2.20-4.16; P < .001). Significant but moderate reductions in the risk for stent thrombosis or composite ischemic events were observed, without a significant effect on overall mortality. For the net clinical benefit, treatment with new-generation oral anticoagulant agents provided no advantage over placebo (odds ratio, 0.98; 95% CI, 0.90-1.06; P = .57).
The use of anti-Xa or direct thrombin inhibitors is associated with a dramatic increase in major bleeding events, which might offset all ischemic benefits in patients receiving antiplatelet therapy after an ACS.
尽管接受了双联抗血小板治疗，但急性冠状动脉综合征（ACS）患者仍面临血栓形成事件的重大风险。在这种情况下，口服活化Xa拮抗剂（抗Xa）和直接凝血酶抑制剂的作用存在争议。我们的研究目的是评估新一代口服抗凝剂与安慰剂相比，在ACS后接受抗血小板治疗的患者中的疗效和安全性。
检索电子数据库，以确定评估抗Xa或直接凝血酶抑制剂对ACS后接受抗血小板治疗患者影响的前瞻性随机安慰剂对照临床试验。疗效指标包括支架血栓形成、总死亡率以及主要缺血事件的复合终点，而心肌梗死溶栓定义的主要出血事件用作安全性终点。净临床获益计算为复合缺血事件和主要出血事件的总和。
在2000年1月1日至2011年12月31日期间，我们确定了7项符合研究标准的前瞻性随机安慰剂对照临床试验，涉及31286名患者。根据汇总结果，在ACS后接受抗血小板治疗的患者中使用新一代口服抗凝剂与主要出血事件的显著增加相关（优势比，3.03；95%CI，2.20-4.16；P<.001）。观察到支架血栓形成或复合缺血事件风险有显著但适度的降低，对总死亡率无显著影响。对于净临床获益，新一代口服抗凝剂治疗与安慰剂相比没有优势（优势比，0.98；95%CI，0.90-1.06；P=0.57）。
使用抗Xa或直接凝血酶抑制剂与主要出血事件的显著增加相关，这可能抵消ACS后接受抗血小板治疗患者的所有缺血获益。
