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FDA工作人员审查建议扩大利伐沙班的适应症

来源:环球医学编译    时间:2012年05月23日    点击数:    5星

5月23日消息 - 环球医学据悉,FDA的工作人员审查已同意将利伐沙班(拜瑞妥)的适应症扩大到用于减少急性冠脉综合征患者的血栓心血管事件风险。

FDA心血管和肾脏药物咨询委员会将在周三召开会议,以讨论杨森制药的这种每日口服一次Xa因子抑制剂的补充申请。利伐沙班已被批准用于非瓣膜性房颤患者预防中风,以及用于关节置换手术患者预防深静脉血栓的形成。

FDA的工作人员在周一公布的简报文件中写道,利伐沙班似乎能够有效减少急性冠脉综合征(ACS)患者的心血管死亡率。

FDA的工作人员分析了杨森公司的ATLAS试验,该试验在超过19000例ACS患者中对利伐沙班+阿司匹林同时联合噻吩并吡啶或不联合噻吩并吡啶的安全性及有效性进行了评估。

FDA的审查人员写道,与服用安慰剂者相比,服用利伐沙班患者的复合终点(心血管疾病死亡、心肌梗死或卒中)发生率显著降低。他们还表示,导致该终点发生率下降的主要因素是心血管疾病死亡率的下降,“两组间的心肌梗死差异不大,而缺血性卒中则没有差异。”

虽然评审对利伐沙班用于ACS给予了一个积极的整体评价,但两种剂量研究的不一致性还是引起了人们的关注。

例如,与服用安慰剂者相比,接受2.5mg利伐沙班治疗者的复合终点(心血管疾病死亡、心肌梗死或卒中)发生率有所降低;但服用5mg利伐沙班者则未显示出其复合终点有统计学上显著的减少。

此外,5mg利伐沙班还会增加出血的风险,但可降低心肌梗死的风险,“这多少有些意外,”据审查结果显示。

审查还指出该研究缺失数据,即超过2400名患者在试验早期就退出了研究,而且“随访不完整,未对死亡计数。”

FDA工作人员写道,“缺失的数据量……可能会影响到试验的总体解释”,但他补充说,缺失数据对心血管药物来说是的常见问题,尽管数据存在漏洞,但仍建议批准该药。

“总体来说,拜瑞妥的获益风险比似乎是有利的,主要是因为其能够降低(心血管疾病)死亡率,尽管大出血和致命出血的风险有所增加,”FDA的审查人员得出结论。“这些评估表明,拜瑞妥的益处大于风险。”

专家小组将在周三进行投票,以决定是否应该批准利伐沙班用于ACS,以及如果建议批准该药,其是否应当携带关于出血风险的黑框警告。

预计FDA将在6月底之前对利伐沙班作出最终决定。FDA并非必须遵循其咨询委员会的意见,但通常还是会遵循的。(环球医学)

原文:

FDA Staff Likes Xarelto for ACS

An FDA staff review has endorsed expanding the indications for rivaroxaban (Xarelto) to include reducing the risk of thrombotic cardiovascular events in patients with acute coronary syndrome.

The agency's Cardiovascular and Renal Drugs Advisory Committee will meet Wednesday to discuss the supplemental application for Janssen Pharmaceutical's oral, once-daily, factor Xa inhibitor. Rivaroxaban is already approved for prevention of stroke in patients with nonvalvular atrial fibrillation, and prevention of deep vein thrombosis in patients undergoing joint replacement surgery.

The drug appears to work well at reducing the rate of cardiovascular death in patients with acute coronary syndrome (ACS), wrote FDA staff in briefing documents released Monday.

FDA staff analyzed Janssen's ATLAS trials, which evaluated the safety and efficacy of rivaroxaban in more than 19,000 ACS patients in addition to aspirin with or without thienopyridine therapy.

Patients taking rivaroxaban had a significant reduction in the occurrence of the composite primary endpoint of cardiovascular death, myocardial infarction, or stroke, compared with placebo, FDA reviewers wrote. They added that the main factor driving the endpoint was a reduction in cardiovascular death, "with little difference on myocardial infarction and no difference on ischemic stroke."

While the review gave rivaroxaban for ACS an overall positive review, it raised concerns about an inconsistency between the two doses studied.

For instance, patients treated with the 2.5-mg dose of rivaroxaban had a reduced occurrence of the composite primary endpoint of cardiovascular death, myocardial infarction, or stroke, compared with placebo, but the 5-mg dose did not show a statistically significant reduction in the primary endpoint.

In addition, the 5-mg dose also increased the risk of bleeding, but decreased the risk of MI, "which was somewhat unexpected," according to the review.

The review also pointed to missing data in the study, namely the more than 2,400 patients who dropped out of the trials early, and to "incomplete follow-up and uncounted deaths."

"The quantity of missing data ... could affect the overall interpretability of the trial," staff wrote, but added that missing data is a common problem for cardiovascular drugs, and still recommended approval despite the holes in the data.

"Overall, the benefit-risk ratio for Xarelto appears to be favorable, predominantly because there is a reduction in [cardiovascular] death, despite an increased risk of major and fatal bleeding," the FDA reviewers concluded. "These estimates suggest that the benefit of Xarelto outweighs the risk."

Wednesday's panel will be asked to vote on whether rivaroxaban should be approved for ACS, and if so, whether the drug should carry a box warning about the bleeding risk.

The FDA is expected to make a final decision on rivaroxaban by the end of June. The agency does not have to follow the advice of its advisory committees, but it often does.
 

相关链接:http://www.medpagetoday.com/Cardiology/AcuteCoronarySyndrome/32808 

 

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