Singh Sarabjeet, Molnar Janos, Arora Rohit
Department of Medicine, Chicago Medical School, Illinois, USA.
J Cardiovasc Pharmacol Ther. 2007 Dec;12(4):283-91. doi: 10.1177/1074248407306589.
Recent data suggest that bivalirudin, a reversible direct thrombin inhibitor, may be noninferior to heparins (unfractionated heparin/low molecular weight heparin) in providing protection against cardiovascular events, with significantly fewer bleeding complications. Whether this advantage is consistent has not been fully defined. We evaluated cardiac outcomes with bivalirudin vs the heparins in management of acute coronary syndromes (ACS), including patients undergoing percutaneous coronary interventions (PCI). Formal computer-aided searches of electronic databases (MEDLINE, PubMed, Cochrane Controlled Trials Registry) were performed by scrutiny of the reference lists of trials and review articles, abstracts, meeting proceedings, and the manufacturers of direct thrombin inhibitors. Five randomized controlled trials (BAT, 1995; CACHET, 2002; REPLACE-2, 2003; REPLACE-1, 2004; and ACUITY, 2006) comparing bivalirudin to the heparins in patients with ACS, including patients undergoing PCI, were identified. The meta-analysis consisted of 25 457 patients (bivalirudin, 15 077; heparins, 10 380). The primary safety end point was major bleeding, defined as intracranial, intraocular, or retroperitoneal hemorrhage; clinically overt blood loss leading to a hemoglobin drop exceeding 3 g/dL (or 10% of hematocrit) and transfusion of 2 or more units of whole blood or packed red blood cells. The combined relative risks (RR) across all of the studies and the 95% confidence intervals of death, myocardial infarction (MI), and revascularization (bivalirudin vs heparins) were computed using the Mantel-Haenszel fixed-effect model, whereas the random-effect model was used for major bleeding. A 2-sided alpha error < .05 was considered to be significant. There were no significant differences in patient characteristics between the 2 groups. Compared to the heparins, the risk of death, MI, revascularization, and composite ischemic end points were similar with bivalirudin monotherapy. However, the risk of major bleeding was significantly lower with bivalirudin use (RR = 0.553; 95% CI = 0.402-0.761; P = .001). The present meta-analysis suggests that bivalirudin may be noninferior to the heparins in reducing the composite of ischemic end points. Additionally, compared to the heparins, bivalirudin monotherapy may lower the rate of major bleeding.
近期数据表明，比伐卢定作为一种可逆性直接凝血酶抑制剂，在预防心血管事件方面可能不劣于肝素（普通肝素/低分子量肝素），且出血并发症显著减少。这一优势是否始终存在尚未完全明确。我们评估了在急性冠状动脉综合征（ACS）管理中，包括接受经皮冠状动脉介入治疗（PCI）的患者，使用比伐卢定与肝素的心脏结局。通过仔细查阅试验和综述文章的参考文献列表、摘要、会议记录以及直接凝血酶抑制剂的制造商，对电子数据库（MEDLINE、PubMed、Cochrane对照试验注册库）进行了正式的计算机辅助检索。共识别出五项比较比伐卢定与肝素在ACS患者（包括接受PCI的患者）中的随机对照试验（BAT，1995年；CACHET，2002年；REPLACE - 2，2003年；REPLACE - 1，2004年；以及ACUITY，2006年）。荟萃分析纳入了25457例患者（比伐卢定组15077例；肝素组10380例）。主要安全终点为大出血，定义为颅内、眼内或腹膜后出血；临床上明显的失血导致血红蛋白下降超过3 g/dL（或血细胞比容的10%）以及输注2个或更多单位的全血或浓缩红细胞。使用Mantel - Haenszel固定效应模型计算所有研究中死亡、心肌梗死（MI）和血运重建（比伐卢定与肝素相比）的合并相对风险（RR）及95%置信区间，而随机效应模型用于大出血情况。双侧α错误<0.05被认为具有统计学意义。两组患者的特征无显著差异。与肝素相比，比伐卢定单药治疗在死亡、MI、血运重建以及复合缺血终点的风险方面相似。然而，使用比伐卢定的大出血风险显著更低（RR = 0.553；95% CI = 0.402 - 0.761；P = 0.001）。本荟萃分析表明，比伐卢定在降低复合缺血终点方面可能不劣于肝素。此外，与肝素相比，比伐卢定单药治疗可能降低大出血发生率。
