欧盟批准利伐沙班用于急性冠脉综合征二级预防

欧盟委员会已批准利伐沙班(rivaroxaban)联合抗血小板治疗预防急性冠脉综合征(ACS)事件后动脉粥样硬化血栓形成事件。

该药物获准用于心脏生物标志物水平升高成人患者的剂量为2.5 mg，每日2次。

该项获批在意料之中，因为欧洲药品管理局人用医疗产品委员会已于3月21日推荐利伐沙班用于该适应证。利伐沙班在美国由强生旗下的杨森制药公司负责销售，而其他国家和地区则由拜耳医疗保健公司负责上市，商品名为拜瑞妥(Xarelto)。

这项用于二级预防的批准令的依据是涉及15,500多例患者的ATLAS ACS 2-TIMI 51(抗-Xa治疗联合阿司匹林或阿司匹林+噻吩并吡啶类药物减少急性冠脉综合征患者心血管事件)研究结果。拜耳公司称，在这项研究中，与单纯接受标准抗血小板治疗[小剂量阿司匹林或小剂量阿司匹林+噻吩并吡啶类(氯吡格雷或噻氯吡啶)]相比，利伐沙班2.5 mg、每日2次添加治疗可显著减少近期ACS患者心血管死亡、心肌梗死或卒中的复合主要疗效终点。

该公司指出，基于上述试验结果，欧洲心脏病学会(ESC)2012版指南推荐利伐沙班可用于接受阿司匹林和氯吡格雷抗血小板治疗且出血风险较低的ST段抬高心肌梗死(STEMI)患者。

哈佛大学医学院PERFUSE研究小组主席、ATLAS ACS的主要研究者C. Michael Gibson博士在拜耳公司发布的一份声明中指出，由于ACS事件后凝血酶长时间维持在较高水平，这些患者面临较高的二次事件风险。“ATLAS ACS 2-TIMI 51研究表明，使用小剂量利伐沙班联合标准抗血小板治疗这些患者时，可靶向作用于血凝块形成的两个途径，因而提供更加完全的长期保护，包括显著减少死亡风险。”

杨森公司仍在等待美国食品药品管理局(FDA)对ACS患者二级预防适应证的批准。该公司于2011年首次提出批准申请，1年后，FDA要求提供更多数据。2012年5月，FDA顾问小组投票反对批准该适应证。今年3月，FDA再次声称，仍存在一些悬而未决的问题有待解决。

该药物于2011年首次获准用于预防髋关节或膝关节置换术患者深静脉血栓形成(DVT)或肺栓塞(PE)。目前已有另外5项适应证在美国获批，包括DVT 或PE治疗和减少初治后DVT 及PE复发。利伐沙班已在120个国家获准上市。

爱思唯尔版权所有  未经授权请勿转载

By: ALICIA AULT, Cardiology News Digital Network

The European Commission has approved the use of rivaroxaban in combination with antiplatelet therapy to help prevent atherothrombotic events after acute coronary syndrome.

The drug was approved at a dose of 2.5 milligrams twice daily in adults with elevated cardiac biomarkers.

The approval was expected, as the European Medicines Agency Committee for Medicinal Products for Human Use recommended rivaroxaban for the indication on March 21. Rivaroxaban is marketed outside the United States by Bayer HealthCare and in the United States by Janssen Pharmaceuticals, Inc., a division of Johnson & Johnson, as Xarelto.

The approval for secondary prevention was based on results from the ATLAS ACS 2-TIMI 51 (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Aspirin With/Without Thienopyridine Therapy in Subjects With Acute Coronary Syndrome) study of more than 15,500 patients. In the trial, rivaroxaban 2.5 mg twice daily added to standard antiplatelet therapy – low-dose aspirin with or without a thienopyridine (clopidogrel or ticlopidine) – significantly reduced the composite primary efficacy endpoint of cardiovascular death, myocardial infarction, or stroke in patients after a recent ACS compared to those who received standard antiplatelet therapy alone, according to Bayer.

Based on that trial, the 2012 European Society of Cardiology guidelines recommended that treatment with rivaroxaban be considered for patients with ST-segment elevation myocardial infarction (STEMI) who are at low bleeding risk and on antiplatelet therapy with aspirin and clopidogrel, the company said.

In a statement issued by Bayer, Dr. C. Michael Gibson, Chairman of the PERFUSE Study Group at Harvard Medical School and the Principal Investigator in the ATLAS ACS studies, said that ACS patients are at risk for secondary events because thrombin levels remain elevated long afterwards. "In the ATLAS ACS 2-TIMI 51 study, we’ve shown that treating these patients with a low dose of rivaroxaban in combination with standard antiplatelet therapy targets both pathways of clot formation, providing more complete long-term protection, including significant reduction in mortality risk," said Dr. Gibson.

Janssen awaits Food and Drug Administration approval for secondary prevention for patients with ACS. The company first sought approval in 2011. A year later, the FDA requested more data. In May 2012, an FDA advisory panel voted against approval of the indication. In March this year, the FDA again said there were outstanding issues that needed to be addressed.

The drug was first approved in 2011 for prophylaxis of deep vein thrombosis or pulmonary embolism in patients undergoing hip or knee replacement surgery. It now has five additional approvals in the United States, including the treatment of DVT or PE and for reducing the recurrence of DVT and PE after initial treatment. Rivaroxaban is approved in 120 countries.