Division of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University, Ubon Ratchathani, Thailand.
Department of Pharmacy, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Lancet. 2017 Aug 19;390(10096):747-759. doi: 10.1016/S0140-6736(17)31441-1.
Fibrinolytic therapy offers an alternative to mechanical reperfusion for ST-segment elevation myocardial infarction (STEMI) in settings where health-care resources are scarce. Comprehensive evidence comparing different agents is still unavailable. In this study, we examined the effects of various fibrinolytic drugs on clinical outcomes.
We did a network meta-analysis based on a systematic review of randomised controlled trials comparing fibrinolytic drugs in patients with STEMI. Several databases were searched from inception up to Feb 28, 2017. We included only randomised controlled trials that compared fibrinolytic agents as a reperfusion therapy in adult patients with STEMI, whether given alone or in combination with adjunctive antithrombotic therapy, against other fibrinolytic agents, a placebo, or no treatment. Only trials investigating agents with an approved indication of reperfusion therapy in STEMI (streptokinase, tenecteplase, alteplase, and reteplase) were included. The primary efficacy outcome was all-cause mortality within 30-35 days and the primary safety outcome was major bleeding. This study is registered with PROSPERO (CRD42016042131).
A total of 40 eligible studies involving 128 071 patients treated with 12 different fibrinolytic regimens were assessed. Compared with accelerated infusion of alteplase with parenteral anticoagulants as background therapy, streptokinase and non-accelerated infusion of alteplase were significantly associated with an increased risk of all-cause mortality (risk ratio [RR] 1·14 [95% CI 1·05-1·24] for streptokinase plus parenteral anticoagulants; RR 1·26 [1·10-1·45] for non-accelerated alteplase plus parenteral anticoagulants). No significant difference in mortality risk was recorded between accelerated infusion of alteplase, tenecteplase, and reteplase with parenteral anticoagulants as background therapy. For major bleeding, a tenecteplase-based regimen tended to be associated with lower risk of bleeding compared with other regimens (RR 0·79 [95% CI 0·63-1·00]). The addition of glycoprotein IIb or IIIa inhibitors to fibrinolytic therapy increased the risk of major bleeding by 1·27-8·82-times compared with accelerated infusion alteplase plus parenteral anticoagulants (RR 1·47 [95% CI 1·10-1·98] for tenecteplase plus parenteral anticoagulants plus glycoprotein inhibitors; RR 1·88 [1·24-2·86] for reteplase plus parenteral anticoagulants plus glycoprotein inhibitors).
Significant differences exist among various fibrinolytic regimens as reperfusion therapy in STEMI and alteplase (accelerated infusion), tenecteplase, and reteplase should be considered over streptokinase and non-accelerated infusion of alteplase. The addition of glycoprotein IIb or IIIa inhibitors to fibrinolytic therapy should be discouraged.
None.
在医疗资源匮乏的情况下，纤维蛋白溶解疗法为 ST 段抬高型心肌梗死（STEMI）提供了一种替代机械再灌注的方法。目前仍缺乏比较不同药物的综合证据。本研究旨在比较不同纤维蛋白溶解药物对临床结局的影响。
我们对比较纤维蛋白溶解药物治疗 STEMI 患者的随机对照试验进行了系统评价和网络荟萃分析。从研究开始到 2017 年 2 月 28 日，我们检索了多个数据库。我们只纳入了比较纤维蛋白溶解药物作为 STEMI 患者再灌注治疗的随机对照试验，无论是否单独使用或联合辅助抗栓治疗，与其他纤维蛋白溶解药物、安慰剂或不治疗进行比较。仅纳入了研究具有 STEMI 再灌注治疗批准适应证的药物（链激酶、替奈普酶、阿替普酶和瑞替普酶）的试验。主要疗效终点为 30-35 天内全因死亡率，主要安全性终点为大出血。本研究已在 PROSPERO（CRD42016042131）注册。
共评估了 40 项符合条件的研究，涉及 128071 例接受 12 种不同纤维蛋白溶解方案治疗的患者。与加速输注阿替普酶联合静脉抗凝作为背景治疗相比，链激酶和非加速输注阿替普酶与全因死亡率增加显著相关（链激酶加静脉抗凝剂的风险比[RR]为 1.14[95%CI 1.05-1.24]；非加速输注阿替普酶加静脉抗凝剂的 RR 为 1.26[1.10-1.45]）。与静脉抗凝作为背景治疗时，加速输注阿替普酶、替奈普酶和瑞替普酶之间的死亡率风险无显著差异。在大出血方面，与其他方案相比，替奈普酶方案出血风险较低（RR 0.79[95%CI 0.63-1.00]）。与加速输注阿替普酶联合静脉抗凝相比，将糖蛋白 IIb/IIIa 抑制剂加入纤维蛋白溶解治疗中，大出血风险增加 1.27-8.82 倍（RR 1.47[95%CI 1.10-1.98]替奈普酶加静脉抗凝加糖蛋白抑制剂；RR 1.88[1.24-2.86]瑞替普酶加静脉抗凝加糖蛋白抑制剂）。
STEMI 再灌注治疗中不同纤维蛋白溶解方案之间存在显著差异，阿替普酶（加速输注）、替奈普酶和瑞替普酶应优于链激酶和非加速输注的阿替普酶。不鼓励将糖蛋白 IIb/IIIa 抑制剂加入纤维蛋白溶解治疗中。
本研究的局限性在于大多数试验都是在过去 20 年进行的，可能无法反映当前纤维蛋白溶解药物的应用情况。
