Cardiovascular and Renal Outcomes With Canagliflozin According to Baseline Kidney Function.
Cardiovascular and Renal Outcomes With Canagliflozin According to Baseline Kidney Function.
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DOI：
10.1161/circulationaha.118.035901
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发表时间：
2018-10-09
期刊：
影响因子：
37.8
通讯作者：
Perkovic V
中科院分区：
文献类型：
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作者：
Neuen BL;Ohkuma T;Neal B;Matthews DR;de Zeeuw D;Mahaffey KW;Fulcher G;Desai M;Li Q;Deng H;Rosenthal N;Jardine MJ;Bakris G;Perkovic V
补充数字内容可在文本中找到。卡格列净被批准用于2型糖尿病的降糖治疗，并具有心血管和肾脏益处。我们试图评估它是否对慢性肾脏疾病患者有益，包括估计肾小球滤过率（eGFR）在30至45 mL/min/1.73 m2之间的患者，这些患者目前尚未批准使用该药物。CANVAS项目将10142名eGFR >30 mL/min/1.73 m2的2型糖尿病受试者随机分配至卡格列净或安慰剂组。主要结局是心血管死亡、非致死性心肌梗死或非致死性卒中以及其他心血管、肾脏和安全性结局的复合终点。该次要分析描述了患有和不患有慢性肾脏疾病的参与者的结局，定义为eGFR <60和≥60 mL/min/1.73 m2，并根据基线肾功能（eGFR <45，45至<60，60至<90和≥90 mL/min/1.73 m2）。基线时，2039名（20.1%）参与者的eGFR <60 mL/min/1.73 m2，其中71.6%有心血管疾病史。卡格列净对慢性肾脏疾病患者（风险比，0.70; 95% CI，0.55-0.90）和肾功能保留患者（风险比，0.92; 95% CI，0.79-1.07; P异质性= 0.08）的主要结局的影响相似。eGFR亚组对大多数心血管和肾脏结局的相对影响相似，仅提示致死性/非致死性卒中结局可能存在异质性（P异质性= 0.01），几乎所有安全性结局的结果也是如此。在2型糖尿病和心血管疾病病史或高风险人群中，卡格列净对心血管和肾脏结局的影响未因基线肾功能水平而改变，eGFR水平降至30 mL/min/1.73 m2。重新评估目前在慢性肾脏疾病中使用Canagliflozin的局限性可能会使更多的人从这种治疗中受益。URL：https://www.clinicaltrials.gov。唯一标识符：NCT 01032629、NCT 01989754。
Supplemental Digital Content is available in the text. Canagliflozin is approved for glucose lowering in type 2 diabetes and confers cardiovascular and renal benefits. We sought to assess whether it had benefits in people with chronic kidney disease, including those with an estimated glomerular filtration rate (eGFR) between 30 and 45 mL/min/1.73 m2 in whom the drug is not currently approved for use. The CANVAS Program randomized 10 142 participants with type 2 diabetes and eGFR >30 mL/min/1.73 m2 to canagliflozin or placebo. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, with other cardiovascular, renal, and safety outcomes. This secondary analysis describes outcomes in participants with and without chronic kidney disease, defined as eGFR <60 and ≥60 mL/min/1.73 m2, and according to baseline kidney function (eGFR <45, 45 to <60, 60 to <90, and ≥90 mL/min/1.73 m2). At baseline, 2039 (20.1%) participants had an eGFR <60 mL/min/1.73 m2, 71.6% of whom had a history of cardiovascular disease. The effect of canagliflozin on the primary outcome was similar in people with chronic kidney disease (hazard ratio, 0.70; 95% CI, 0.55–0.90) and those with preserved kidney function (hazard ratio, 0.92; 95% CI, 0.79–1.07; P heterogeneity = 0.08). Relative effects on most cardiovascular and renal outcomes were similar across eGFR subgroups, with possible heterogeneity suggested only for the outcome of fatal/nonfatal stroke (P heterogeneity = 0.01), as were results for almost all safety outcomes. The effects of canagliflozin on cardiovascular and renal outcomes were not modified by baseline level of kidney function in people with type 2 diabetes and a history or high risk of cardiovascular disease down to eGFR levels of 30 mL/min/1.73 m2. Reassessing current limitations on the use of canagliflozin in chronic kidney disease may allow additional individuals to benefit from this therapy. URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01032629, NCT01989754.