Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes
Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes
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DOI：
10.1056/nejmoa1611925
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发表时间：
2017-08-17
影响因子：
158.5
通讯作者：
Matthews, David R.
中科院分区：
文献类型：
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作者：
Neal, Bruce;Perkovic, Vlado;Matthews, David R.
Canagliflozin是一种钠-葡萄糖协同转运蛋白2抑制剂，可降低糖尿病患者的血压、体重和蛋白尿。我们报告的效果与卡格列净治疗对心血管，肾脏，和安全outcomes. METHODS CANVAS程序整合数据从两个试验，共涉及10,142名参与者与2型糖尿病和心血管高风险。每项试验的参与者被随机分配接受卡格列净或安慰剂，平均随访188.2周。主要结局是心血管原因死亡、非致命性心肌梗死或非致命性卒中的复合终点。研究参与者的平均年龄为63.3岁，35.8%为女性，糖尿病的平均病程为13.5年，65.6%有心血管疾病史。卡格列净组的主要结局发生率低于安慰剂组（每1000患者-年发生26.9例受试者vs 31.5例受试者;风险比为0.86; 95%置信区间[CI]为0.75 - 0.97;非劣效性P< 0.001;优效性P = 0.02）。尽管根据预先规定的假设检验序列，肾脏结局不具有统计学显著性，但结果显示卡格列净在白蛋白尿进展方面可能获益（风险比，0.73; 95%CI，0.67 - 0.79）和估计肾小球滤过率持续降低40%的复合结局，需要肾脏替代治疗或肾脏原因死亡（风险比，0.60; 95% CI，0.47 - 0.77）。除了截肢风险增加外，不良反应与先前报告的卡格列净相关风险一致（6.3 vs. 3.4例受试者/1000患者-年;风险比，1.97; 95% CI，1.41 - 2.75）;截肢主要是在脚趾或跖骨的水平。结论在两项试验中，涉及2型糖尿病患者和高血糖患者，在心血管疾病风险方面，接受卡格列净治疗的患者发生心血管事件的风险低于接受安慰剂治疗的患者，但截肢的风险较高，主要发生在脚趾或跖骨水平。
BACKGROUNDCanagliflozin is a sodium-glucose cotransporter 2 inhibitor that reduces glycemia as well as blood pressure, body weight, and albuminuria in people with diabetes. We report the effects of treatment with canagliflozin on cardiovascular, renal, and safety outcomes.METHODSThe CANVAS Program integrated data from two trials involving a total of 10,142 participants with type 2 diabetes and high cardiovascular risk. Participants in each trial were randomly assigned to receive canagliflozin or placebo and were followed for a mean of 188.2 weeks. The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke.RESULTSThe mean age of the participants was 63.3 years, 35.8% were women, the mean duration of diabetes was 13.5 years, and 65.6% had a history of cardiovascular disease. The rate of the primary outcome was lower with canagliflozin than with placebo (occurring in 26.9 vs. 31.5 participants per 1000 patient-years; hazard ratio, 0.86; 95% confidence interval [CI], 0.75 to 0.97; P< 0.001 for noninferiority; P = 0.02 for superiority). Although on the basis of the prespecified hypothesis testing sequence the renal outcomes are not viewed as statistically significant, the results showed a possible benefit of canagliflozin with respect to the progression of albuminuria (hazard ratio, 0.73; 95% CI, 0.67 to 0.79) and the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate, the need for renal-replacement therapy, or death from renal causes (hazard ratio, 0.60; 95% CI, 0.47 to 0.77). Adverse reactions were consistent with the previously reported risks associated with canagliflozin except for an increased risk of amputation (6.3 vs. 3.4 participants per 1000 patient-years; hazard ratio, 1.97; 95% CI, 1.41 to 2.75); amputations were primarily at the level of the toe or metatarsal.CONCLUSIONSIn two trials involving patients with type 2 diabetes and an elevated risk of cardiovascular disease, patients treated with canagliflozin had a lower risk of cardiovascular events than those who received placebo but a greater risk of amputation, primarily at the level of the toe or metatarsal.