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塞来昔布、萘普生或布洛芬治疗关节炎的心血管安全性研究
Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis


Steven E. Nissen ... 心脑血管疾病 • 2016.12.29

COX-2选择性非甾体抗炎药塞来昔布心血管安全性的临床研究

 

栗占国*,张晓盈

北京大学人民医院风湿免疫科

* 通讯作者

 

自2004年9月罗非昔布从全球撤市后,有关非甾体抗炎药的心血管安全性问题便引起学术界的广泛争议。针对塞来昔布的多项随机对照研究结果并不一致1-3。但2016年11月13日《新英格兰医学杂志》在线发表一篇关于长达10年、纳入人数超过2.4万例的PRECISION研究,提示长期接受处方剂量的塞来昔布患者发生心血管事件的风险与接受布洛芬和萘普生治疗的患者相似4

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摘要


背景

与非选择性非甾体抗炎药(NSAID)相比,塞来昔布的心血管安全性仍不确定。

 

方法

因骨关节炎或类风湿关节炎而需要NSAID且处于心血管风险增高的患者被随机分配到塞来昔布组、萘普生组或布洛芬组。本试验目的是评价塞来昔布在心血管死亡(包括出血死亡)、非致死性心肌梗死或非致死性卒中等首要复合结局方面的非劣效性。非劣效性要求风险比≤1.12、97.5%置信上限在意向治疗人群中≤1.33、治疗人群(on-treatment population)中≤1.40。本试验也裁定了胃肠和肾脏结局。

 

结果

共有24,081例患者被随机分配到塞来昔布组(每日剂量均值[±标准差],209±37 mg)、萘普生组(852±103 mg)和布洛芬组(2,045±246 mg),平均治疗时间为20.3±16.0个月,平均随访时间为34.1±13.4个月。试验期间,68.8%的患者停止研究用药,27.4%的患者终止随访。在意向治疗分析中,发生首要结局事件的患者数目在塞来昔布组为188例(2.3%),萘普生组为201例(2.5%),布洛芬组为218例(2.7%)(塞来昔布对萘普生的风险比,0.93;95%置信区间[CI],0.76~1.13;塞来昔布对布洛芬的风险比,0.85;95%置信区间[CI],0.70~1.04;在两组比较中非劣效性P<0.001)。在治疗分析中,塞来昔布组中有134例患者发生首要结局事件(1.7%),萘普生组为144例(1.8%),布洛芬组为155例(1.9%)(塞来昔布对萘普生的风险比,0.90;95% CI,0.71~1.15;塞来昔布对布洛芬的风险比,0.81;95% CI,0.65~1.02;在两项比较中非劣效性P均<0.001)。塞来昔布组胃肠事件的风险显著低于萘普生组(P=0.01),也显著低于布洛芬组(P=0.002);塞来昔布组肾脏事件的风险显著低于布洛芬组(P=0.004),但未显著低于萘普生组(P=0.19)。

 

结论

在心血管安全性方面,我们发现中等剂量的塞来昔布不劣于布洛芬或萘普生(由辉瑞公司资助;在ClinicalTrials.gov编号为NCT00346216)。





作者信息

Steven E. Nissen, M.D., Neville D. Yeomans, M.D., Daniel H. Solomon, M.D., M.P.H., Thomas F. Lüscher, M.D., Peter Libby, M.D., M. Elaine Husni, M.D., David Y. Graham, M.D., Jeffrey S. Borer, M.D., Lisa M. Wisniewski, R.N., Katherine E. Wolski, M.P.H., Qiuqing Wang, M.S., Venu Menon, M.D., Frank Ruschitzka, M.D., Michael Gaffney, Ph.D., Bruce Beckerman, M.D., Manuela F. Berger, M.D., Weihang Bao, Ph.D., and A. Michael Lincoff, M.D., for the PRECISION Trial Investigators*
From the Cleveland Clinic, Cleveland (S.E.N., M.E.H., L.M.W., K.E.W., Q.W., V.M., A.M.L.); Western Sydney University, Campbelltown, NSW, Australia (N.D.Y.); Brigham and Women’s Hospital, Harvard Medical School, Boston (D.H.S., P.L.); University Hospital Zurich, Zurich, Switzerland (T.F.L., F.R.); Baylor College of Medicine, Veterans Affairs Medical Center, Houston (D.Y.G.); and State University of New York, Downstate Health Sciences Center (J.S.B.) and Pfizer (M.G., B.B., M.F.B., W.B.), New York. Address reprint requests to Dr. Nissen at Cleveland Clinic J2-230, 9500 Euclid Ave., Cleveland, OH 44195, or at nissens@ccf.org. *A complete list of the committees, study centers, and investigators participating in the Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen (PRECISION) trial is provided in the Supplementary Appendix, available at NEJM.org.

 

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