SILVER SPRING, Maryland (EGMN) – A U.S. Food and Drug Administration advisory panel on Sept. 20 unanimously voted to recommend that dabigatran, an orally administered direct thrombin inhibitor, be approved for reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.

The panel based the decision on the results of the Randomized Evaluation of Long Term Anticoagulant Therapy (RE-LY) trial, a noninferiority, randomized international study of 18,113 patients with nonvalvular atrial fibrillation (AF) and at least one risk factor for stroke, which compared two blinded doses of dabigatran to open-label warfarin on the incidence of stroke and systemic embolism, the primary end point.

Both doses of dabigatran were considered noninferior to warfarin for preventing stroke and systemic embolism, and the 150 mg dose was more effective than warfarin and the 100 mg dose in preventing stroke and systemic embolism, according to the company, Boehringer Ingelheim Pharmaceuticals Inc. Both doses were associated with a reduction in hemorrhagic stroke and when compared to warfarin, the vascular death risk was reduced with the higher dose.

Compared to warfarin, the 150 mg dose was associated with a significantly increased risk of major GI bleeding, but also associated with a significant reduction in life-threatening and total bleeding. The 110 mg dose was also associated with a significant reduction in major, life-threatening, and total bleeding, when compared to warfarin. More patients on dabigatran had myocardial infarctions (1.4% and 1.5% among those on 110 mg and 150 mg, compared with 1.1% of those on warfarin).

The panel agreed that the study provided strong evidence that both dabigatran doses had been shown to be noninferior to warfarin therapy in the study, and several said they believed the 150 mg dose had been shown to be superior to warfarin.

Of the five cardiologists on the panel, three supported approval of the 150 mg dose only, because they were concerned that if both doses were available, clinicians might primarily prescribe the lower dose as the “default” dose because of fears over adverse events with the lower dose, and many patients would be deprived of a drug they considered more effective than warfarin.

Dabigatran was approved in 2008 in the European Union, Canada, Australia, Brazil and other countries for primary prevention of venous thromboembolic events in adults who have undergone elective be total hip replacement or total knee replacement surgery, according to Boehringer. It is marketed under the trade name Pradaxa, which will also be the trade name in the United States, if approved by the FDA.

The FDA’s decision is expected by Oct. 19. The FDA usually follows the recommendations of its advisory panels. Panel members are cleared of disclosures related to the topic of the meeting, although occasionally, are granted waivers.

 

Copyright (c) 2010 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

马里兰州银泉市(EGMN)——美国食品药品管理局(FDA)于9月20日批准将达比加群酯(一种口服直接凝血酶抑制剂)用于非瓣膜性心房纤颤患者(AF)，以降低其发生卒中和全身性血管栓塞的风险。

 

RE-LY试验(评价抗凝疗法长期效果的随机研究)的结果是FDA做出以上决定的依据。RE-LY试验是一项纳入18,113例非瓣膜性AF患者(所有患者均具备至少1项以上卒中风险因素)的非劣性随机化国际研究，其主要终点是卒中和全身性血管栓塞的发病率。

 

RE-LY试验对比了两种不同剂量的达比加群酯(盲法给药)和华法林(开标签给药)的疗效。结果发现，在预防卒中和全身性血管栓塞方面，150 mg的达比加群酯效果优于华法林和100 mg的达比加群酯。与华法林相比，两种剂量的达比加群酯均可降低患者出血性卒中的发病率，150 mg组还可以降低患者的心血管死亡风险。

 

与华法林相比，服用达比加群酯150 mg会使患者胃肠道(GI)大出血的风险显著升高，但患者出现大出血危象的几率显著降低，总出血量也显著减少。110 mg的达比加群酯在预防大出血危象和降低总出血量方面同样比华法林表现更佳。但服用达比加群酯的患者发生心肌梗死的几率更高(110 mg和150 mg组分别为1.4%和1.5%，华法林组为1.1%)。

 

该研究提供的证据表明，两种剂量的达比加群酯在疗效上均不劣于华法林，150 mg剂量的达比加群酯比华法林疗效更佳。在专家小组的5位心脏病学家中，有3位赞同仅应批准150 mg剂量的达比加群酯，因为他们担心一旦两种剂量都获得批准，临床医生因为担心高剂量会引发更多不良事件，会倾向于将低剂量作为“默认”剂量，便可能会有大量患者不再有机会接受更好的治疗。

 

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