目的系统评价Vorapaxar治疗动脉粥样硬化疾病的安全性和有效性。方法检索PubMed、Embase、Cochrane Central Register of Controlled Trials、CNKI全文数据库,收集自建库以来至2014年10月公开发表的有关Vorapaxar治疗动脉粥样硬化疾病...目的系统评价Vorapaxar治疗动脉粥样硬化疾病的安全性和有效性。方法检索PubMed、Embase、Cochrane Central Register of Controlled Trials、CNKI全文数据库,收集自建库以来至2014年10月公开发表的有关Vorapaxar治疗动脉粥样硬化疾病的随机对照试验（RCT）。采用RevMan5.1软件进行系统评价和Meta分析。结果共纳入5项RCT,Meta分析显示：Vorapaxar组以心源性死亡（CV）、心肌梗死（MI）和卒中为复合终点事件发生率（OR=0.87,95%CI 0.81～0.93,P〈0.01）、主要不良心脑血管事件（MACCE）发生率（OR=0.89,95%CI 0.84～0.95,P〈0.01）、CV和MI发生率（OR=0.87,95%CI 0.81～0.93,P〈0.01）、MI发生率（OR=0.85,95%CI 0.78～0.92,P〈0.01）低于安慰剂组,而出血发生率（OR=1.48,95%CI 1.39～1.57,P〈0.01）以及颅内出血发生率（OR=2.36,95%CI 1.40～3.98,P=0.01）高于安慰剂组。结论在治疗动脉粥样硬化疾病时,Vorapaxar虽然在出血发生率和颅内出血发生率上显著高于安慰剂组,但能显著减少CV、MI和卒中为复合终点事件发生率、MACCE发生率、CV和MI发生率及MI发生率。Vorapaxar可成为治疗动脉粥样硬化疾病的新选择。展开更多
Background Vorapaxar reduces cardiovascular death, myocardial infarction （MI）, or stroke in patients with previous MI while increasing bleeding. Patients with diabetes mellitus （DM） are at high risk of recurrent t...Background Vorapaxar reduces cardiovascular death, myocardial infarction （MI）, or stroke in patients with previous MI while increasing bleeding. Patients with diabetes mellitus （DM） are at high risk of recurrent thrombotic events despite standard therapy and may derive particular benefit from antithrombotic therapies. The Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-TIMI 50 trial was a randomized, double-blind, placebo-controlled trial of vorapaxar in patients with stable atherosclerosis.展开更多
Significant progress was achieved in the search of a thrombin receptor antagonist as a novel antithrombotic treatment since the thrombin receptor (protease-activated receptor-1, PAR-1) was cloned 20 years ago. Previou...Significant progress was achieved in the search of a thrombin receptor antagonist as a novel antithrombotic treatment since the thrombin receptor (protease-activated receptor-1, PAR-1) was cloned 20 years ago. Previous works have shown that it is possible to develop potent thrombin receptor antagonists to compete effectively with the receptor’s internal “tethered” ligand to block platelet activation. Vorapaxar (SCH 530348) from Schering-Plough (now Merck) and atopaxar (E5555) from Eisai have been advanced to human clinical trials. Recently, the pivotal phase III clinical trial results for vorapaxar were published. In this article we review these results plus the phase II results from atopaxar. Several newly described thrombin receptor antagonists from the literature will also be discussed. The phase III results from vorapaxar demonstrated that a thrombin receptor antagonist can achieve efficacy in addition to current standard- of-care in treating atherothrombotic patients, especially those with previous myocardial infarction (MI). However, the increased moderate and severe bleeding, especially intracranial bleeding, point to the limitations of current thrombin receptor antagonists. Future thrombin receptor antagonists that can improve on the efficacy and bleeding profile of current ones should have a promising place in meeting the unmet medical need in treating atherothrombotic patients using current standard therapy.展开更多
文摘Background Vorapaxar reduces cardiovascular death, myocardial infarction （MI）, or stroke in patients with previous MI while increasing bleeding. Patients with diabetes mellitus （DM） are at high risk of recurrent thrombotic events despite standard therapy and may derive particular benefit from antithrombotic therapies. The Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-TIMI 50 trial was a randomized, double-blind, placebo-controlled trial of vorapaxar in patients with stable atherosclerosis.
文摘Significant progress was achieved in the search of a thrombin receptor antagonist as a novel antithrombotic treatment since the thrombin receptor (protease-activated receptor-1, PAR-1) was cloned 20 years ago. Previous works have shown that it is possible to develop potent thrombin receptor antagonists to compete effectively with the receptor’s internal “tethered” ligand to block platelet activation. Vorapaxar (SCH 530348) from Schering-Plough (now Merck) and atopaxar (E5555) from Eisai have been advanced to human clinical trials. Recently, the pivotal phase III clinical trial results for vorapaxar were published. In this article we review these results plus the phase II results from atopaxar. Several newly described thrombin receptor antagonists from the literature will also be discussed. The phase III results from vorapaxar demonstrated that a thrombin receptor antagonist can achieve efficacy in addition to current standard- of-care in treating atherothrombotic patients, especially those with previous myocardial infarction (MI). However, the increased moderate and severe bleeding, especially intracranial bleeding, point to the limitations of current thrombin receptor antagonists. Future thrombin receptor antagonists that can improve on the efficacy and bleeding profile of current ones should have a promising place in meeting the unmet medical need in treating atherothrombotic patients using current standard therapy.
