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卡格列净治疗2型糖尿病的心血管和肾脏事件风险研究
Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes


Bruce Neal ... 心脑血管疾病 糖尿病 • 2017.08.17
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2型糖尿病治疗新药有效而安全还是有效

——从CANVAS研究谈降糖新药的心血管安全性临床研究

 

翁建平†‡§*,朱大龙¶‖

†广东省糖尿病防治研究中心;‡中山大学糖尿病研究所;§中山大学附属第三医院内分泌与代谢病学科;¶南京大学医学院;‖南京鼓楼医院内分泌科

*通讯作者

 

2017年6月12日,《新英格兰医学杂志》在线发布了卡格列净心血管安全性与有效性评估研究,即CANVAS和CANVAS-R(称为CANVAS项目)合并研究结果1,2。该研究前者(CANVAS)始于2009年12月,在卡格列净2013年3月获得美国食品药品监督管理局(FDA)批准之前,后者始于2014年1月3,4。研究结果之新可以从2017年2月获得研究最后一个数据来推测,文章发表之快也许可以从6月12日即在线发表来推测,4个月的时间需要完成研究结果分析、文章撰写、投稿、修改、修回等,这一速度与效率是惊人的。

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摘要


背景

卡格列净(canagliflozin)是一种钠葡萄糖协同转运蛋白2(SGLT2)抑制剂,在糖尿病患者中可以降低血糖以及血压、体重和白蛋白尿。我们报告卡格列净在心血管、肾脏和安全性结局方面的疗效。

 

方法

卡格列净心血管评估研究(Canagliflozin Cardiovascular Assessment Study,CANVAS)项目汇集了来自两项试验的数据,纳入共计10,142名2型糖尿病合并高心血管风险的参与者。每项试验中的参与者都被随机分配接受卡格列净或安慰剂,平均接受随访188.2周。主要结局是心血管原因死亡、非致死性心肌梗死或非致死性卒中构成的复合事件。

 

结果

参与者平均年龄为63.3岁,35.8%为女性,糖尿病平均病程为13.5年,65.6%有心血管疾病病史。卡格列净组的主要结局发生率低于安慰剂组(26.9/1,000人年vs. 31.5/1,000人年;风险比,0.86;95%置信区间[CI],075~0.97;非劣效性P<0.001;优效性P=0.02)。尽管根据预设的假设检验序列,我们认为肾脏结局不具有统计学显著性,但结果提示在白蛋白尿进展(风险比,0.73;95% CI,0.67~0.79),以及在估算肾小球滤过率40%持续下降、需要接受肾脏替代治疗或肾原因死亡构成的复合结局(风险比,0.60;95% CI,0.47~0.77)方面,卡格列净可能存在获益。不良反应与之前报道的卡格列净相关风险一致,除了截肢风险增加(6.3/1,000人年vs. 3.4/1,000人年;风险比,1.97;95% CI,1.41~2.75);截肢平面主要在足趾或跖骨。

 

结论

在两项纳入2型糖尿病合并心血管疾病高危患者的试验中,接受卡格列净治疗的患者与接受安慰剂治疗的患者相比,具有较低心血管事件风险,但具有较高截肢风险,主要截肢平面在足趾或跖骨(由杨森研发[Janssen Research and Development]资助;CANVAS和CANVAS-R在ClinicalTrials.gov注册号分别为NCT01032629和NCT01989754)。





作者信息

Bruce Neal, M.B., Ch.B., Ph.D., Vlado Perkovic, M.B., B.S., Ph.D., Kenneth W. Mahaffey, M.D., Dick de Zeeuw, M.D., Ph.D., Greg Fulcher, M.D., Ngozi Erondu, M.D., Ph.D., Wayne Shaw, D.S.L., Gordon Law, Ph.D., Mehul Desai, M.D., and David R. Matthews, D.Phil., B.M., B.Ch., for the CANVAS Program Collaborative Group*
From the George Institute for Global Health, Faculty of Medicine, UNSW Sydney (B.N., V.P.), the Charles Perkins Centre (B.N.), and the Royal North Shore Hospital (V.P., G.F.), University of Sydney, and the Faculty of Medicine, University of New South Wales (B.N.) — all in Sydney; Imperial College London, London (B.N.), and the Oxford Centre for Diabetes, Endocrinology, and Metabolism and Harris Manchester College, University of Oxford, Oxford (D.R.M.) — both in the United Kingdom; the Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, CA (K.W.M.); the University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (D.Z.); and Janssen Research and Development, Raritan, NJ (N.E., W.S., G.L., M.D.). Address reprint requests to Dr. Neal at the George Institute for Global Health, UNSW Sydney, Level 5, 1 King St., Newtown, NSW 2042, Australia, or at bneal@georgeinstitute.org.au. *A complete list of investigators in the Canagliflozin Cardiovascular Assessment Study (CANVAS) Program is provided in the Supplementary Appendix, available at NEJM.org.

 

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