Canagliflozin可降低2型糖尿病患者心血管和肾脏预后的风险。本研究旨在基于估计的肾小球滤过率(eGFR)和尿白蛋白-肌酐比率,评估canagliflozin对不同KDIGO(肾脏疾病:改善全球结果)风险类别的临床结果的相对和绝对影响。
CANagliflozin心血管评估研究(CANVAS)项目的事后分析。
CANVAS计划随机分配了10,142名具有高心血管风险的2型糖尿病患者,其eGFR≥30mL/min/1.73m2,接受canagliflozin或安慰剂治疗。
Canagliflozin或匹配的安慰剂。
主要结局是心血管死亡的复合结果,非致死性心肌梗死,或非致命性中风,与一组其他心血管和肾脏预设的结果。
在10142名参与者中,10,031(98.9%)具有可用的基线eGFR和尿白蛋白-肌酐比值数据。参与者的比例低,moderate-,high,非常高风险的KDIGO类别为58.6%,25.8%,10.6%,和5.0%,分别。canagliflozin对主要结局的相对影响(HR,0.86;95%CI,0.75-0.97)在KDIGO风险类别中一致(P趋势=0.2),其他心血管和肾脏结局的结果相似。在较高的KDIGO风险类别中,主要结局的绝对减少更大(P趋势=0.03),对心血管死亡或因心力衰竭住院的复合(P趋势=0.06)和慢性eGFR斜率(P趋势=0.04)的影响模式相似。
主要是低肾风险人群,较高KDIGO风险类别的参与者相对较少,并排除eGFR<30mL/min/1.73mL的个体。
虽然canagliflozin的相对效应在KDIGO风险类别中是相似的,对于KDIGO风险较高的个体,绝对风险降低可能更大。KDIGO分类系统可能能够识别可能从canagliflozin治疗中获得更大的最终器官保护益处的个体。
这个事后分析没有得到特别资助。最初的CANVAS计划试验由JanssenResearch&Development资助,有限责任公司和作为出资者之间的合作进行的,学术指导委员会,和一个学术研究机构,乔治临床。
CANVAS计划的原始试验已在ClinicalTrials.gov注册,研究编号为NCT01032629和NCT01989754。
Canagliflozin reduces the risk for cardiovascular and kidney outcomes in type 2 diabetes. This study aimed to assess the relative and absolute effects of canagliflozin on clinical outcomes across different KDIGO (Kidney Disease: Improving Global Outcomes) risk categories based on estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio.
Post hoc analysis of the CANagliflozin cardioVascular Assessment Study (CANVAS) Program.
The CANVAS Program randomly assigned 10,142 participants with type 2 diabetes at high cardiovascular risk and with eGFR≥30mL/min/1.73m2 to treatment with canagliflozin or placebo.
Canagliflozin or matching placebo.
The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, with a set of other cardiovascular and kidney prespecified outcomes.
Of 10,142 participants, 10,031 (98.9%) had available baseline eGFR and urinary albumin-creatinine ratio data. The proportion of participants in low-, moderate-, high-, and very high-risk KDIGO categories was 58.6%, 25.8%, 10.6%, and 5.0%, respectively. The relative effect of canagliflozin on the primary outcome (HR, 0.86; 95% CI, 0.75-0.97) was consistent across KDIGO risk categories (P trend=0.2), with similar results for other cardiovascular and kidney outcomes. Absolute reductions in the primary outcome were greater within higher KDIGO risk categories (P trend=0.03) with a similar pattern of effect for the composite of cardiovascular death or hospitalization for heart failure (P trend=0.06) and for chronic eGFR slope (P trend = 0.04).
Predominantly a low kidney risk population, relatively few participants in higher KDIGO risk categories, and exclusion of individuals with eGFR<30mL/min/1.73m2.
Although the relative effects of canagliflozin are similar across KDIGO risk categories, absolute risk reductions are likely greater for individuals at higher KDIGO risk. The KDIGO classification system may be able to identify individuals who might derive greater benefits for end-organ protection from treatment with canagliflozin.
This post hoc analysis was not specifically funded. The original CANVAS Program trials were funded by Janssen Research & Development, LLC and were conducted as a collaboration between the funder, an academic steering committee, and an academic research organization, George Clinical.
The original trials of the CANVAS Program were registered at ClinicalTrials.gov with study numbers NCT01032629 and NCT01989754.