坎格列净在原发性和二级心血管预防组中的 2 型糖尿病和慢性肾脏病患者中的心血管和肾脏结局
Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups.
机构信息
Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, CA (K.W.M.).
George Institute for Global Health, University of New South Wales, Sydney, Australia (M.J.J., S.B., B.N., H.J.L.H., V.P.).
出版信息
Circulation. 2019 Aug 27;140(9):739-750. doi: 10.1161/CIRCULATIONAHA.119.042007. Epub 2019 Jul 11.
BACKGROUND
Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention).
METHODS
In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care.
RESULTS
Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome).
CONCLUSIONS
Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease.
CLINICAL TRIAL REGISTRATION
URL: https://www.clinicaltrials.gov. Unique identifier: NCT02065791.
背景
卡格列净可降低 2 型糖尿病合并慢性肾脏病患者的肾衰竭风险，但对特定心血管结局的影响尚不确定，在无既往心血管疾病（一级预防）的人群中的影响亦不明确。
方法
在 CREDENCE（卡格列净和糖尿病肾病患者的肾脏评估）研究中，4401 名 2 型糖尿病合并慢性肾脏病患者被随机分配至卡格列净组或安慰剂组，两组均在优化的标准治疗基础上进行治疗。
结果
一级预防组（n=2181，49.6%）患者更年轻（61 岁比 65 岁），女性更多（37%比 31%），糖尿病病程更短（15 年比 16 年）。与二级预防组（n=2220，50.4%）相比。卡格列净总体降低了主要心血管事件风险（风险比[HR]，0.80[95%CI，0.67-0.95]；P=0.01），一级预防（HR，0.68[95%CI，0.49-0.94]）和二级预防（HR，0.85[95%CI，0.69-1.06]）预防组均观察到一致的降低（P 组间交互作用=0.25）。心血管死亡（HR，0.78[95%CI，0.61-1.00]）、非致死性心肌梗死（HR，0.81[95%CI，0.59-1.10]）和非致死性卒中（HR，0.80[95%CI，0.56-1.15]）复合终点的各个组分的效果也相似。在一级和二级预防组，主要复合肾脏结局和心血管死亡或心力衰竭住院治疗的复合终点风险也一致降低（每个结局 P 组间交互作用＞0.5）。
结论
卡格列净可显著降低 2 型糖尿病合并慢性肾脏病患者的主要心血管事件和肾衰竭风险，包括无既往心血管疾病的患者。
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