FDA：萘普生的心血管风险可能相对较低

美国食品药品管理局(FDA)表示，非甾体抗炎药(NSAID)萘普生可能比其他选择性或非选择性NSAID具有更低的心血管(CV)血栓栓塞风险。

2月10~11日，FDA关节炎顾问委员会和药物安全与风险管理顾问委员会将举行一场联合会议，FDA是在会前发布的简报中展示上述证据的。在这场会议中，FDA将询问这2个顾问委员会，这些数据是否表明萘普生可能具有较低的CV血栓栓塞风险。FDA还将询问，是否应考虑对可能具有较高CV事件风险的患者给予警告或采取限制，以及当前可用剂量的非处方NSAID是否是可接受的。

根据FDA的简报，萘普生CV安全性特征更佳的主要证据来自一项由牛津大学Coxib和传统NSAID试验者(CNT)协作组织的meta分析。主要研究者于2013年2月向FDA提交了正式出版前的研究副本。这项meta分析同时评估了非选择性NSAID的胃肠道和心血管风险，结论是萘普生的CV血栓栓塞事件风险低于塞来昔布和布洛芬(Lancet 2013;382:769-79)。

FDA已评估了环氧酶2(COX-2)xuanzexing NSAID和非选择性NSAID的安全性特征达10年之久。2005年，关节炎和药物安全性委员会探讨了罗非昔布和塞来昔布的安全性。基于专家组的结论，FDA总结认为，COX-2选择性NSAID和非选择性NSAID均有CV血栓栓塞事件风险。

FDA随后要求辉瑞自行将伐地考昔(Bextra)撤出美国市场，并对所有处方药NSAID增加了一项关于导致严重不良CV事件风险的黑框警告。(默克之前已于2004年自行将罗非昔布撤出美国市场)NSAID还带有关于胃肠道事件风险的警告。为此设计了一份用药指导，以告知患者所有NSAID的CV事件和胃肠道出血风险。生产非选择性NSAID的公司被要求全面审查其已有的对照临床试验数据库，以评估CV安全性。

根据这份简报，牛津的meta分析进一步加强了FDA在2005年时的结论。它还带来了一个问题，即辉瑞是否应当继续其长期研究——塞来昔布总体安全性与布洛芬或萘普生比较的前瞻性随机评估(PRECISION)。2月10~11日的联合顾问委员会会议上将讨论继续这项试验的必要性。

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By: ALICIA AULT, Cardiology News Digital Network

The Food and Drug Administration says that the nonsteroidal anti-inflammatory drug naproxen may carry a lower risk of cardiovascular thromboembolic events than that of other selective or nonselective NSAIDs.

The agency presented evidence for that finding in briefing documents that were issued ahead of a Feb. 10-11 joint meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee.

At that meeting, the FDA will ask the two advisory committees if the data show that naproxen may have a lower risk for CV thrombotic events. The agency also will ask whether warnings or restrictions should be considered for patients who might be at higher risk for CV events, and whether over-the-counter NSAIDs are acceptable at the currently available doses.

According to the documents, the primary evidence for a better cardiovascular safety profile for naproxen comes from a meta-analysis conducted by the Coxib and traditional NSAID Trialists’ (CNT) Collaboration at Oxford University. The principal investigators gave the FDA a prepublication copy of the study in February 2013. The meta-analysis, which assessed both the gastrointestinal and the cardiovascular risks of nonselective NSAIDs, concluded that naproxen had a lower risk of CV thromboembolic events than did celecoxib and ibuprofen (Lancet 2013;382:769-79).

The FDA has been assessing the safety profile of both cyclooxygenase-2 (COX-2) selective NSAIDs and nonselective NSAIDs for almost a decade. In 2005, the arthritis and drug safety committees pondered the safety of rofecoxib and celecoxib. Based on the panels’ conclusions, the FDA concluded that the risk for CV thromboembolic events was present for both COX-2 selective NSAIDs and nonselective NSAIDs.

The agency subsequently asked Pfizer to voluntarily withdraw valdecoxib (Bextra) from the U.S. market, and all prescription NSAIDs were given a boxed warning on the potential for serious adverse CV events. (Merck had previously withdrawn rofecoxib voluntarily from the U.S. market in 2004.) NSAIDs also carry a warning on the potential for gastrointestinal events. A Medication Guide was developed for patients to inform them of the risk of CV events and gastrointestinal bleeding with all NSAIDs. And companies that made nonselective NSAIDs were asked to conduct comprehensive reviews of their existing controlled clinical trial databases to evaluate CV safety.

The Oxford meta-analysis reinforces the agency’s conclusions from 2005, according to the briefing documents. It also brings into question whether Pfizer should continue its long-term study, Prospective Randomized Evaluation of Celecoxib Integrated Safety vs. Ibuprofen or Naproxen (PRECISION), which was begun in the wake of the 2005 panel meeting at the agency’s behest.

The necessity – and wisdom – of continuing that trial is one of the issues that will be discussed at the Feb. 10-11 joint advisory committee meeting.