BACKGROUND Canagliflozin is a sodium glucose cotransporter 2 inhibitor that reduces the risk of cardiovascular events. We report the effects on heart failure (HF) and cardiovascular death overall, in those with and without a baseline history of HF, and in other participant subgroups. METHODS The CANVAS Program (Canagliflozin Cardiovascular Assessment Study) enrolled 10 142 participants with type 2 diabetes mellitus and high cardiovascular risk. Participants were randomly assigned to canagliflozin or placebo and followed for a mean of 188 weeks. The primary end point for these analyses was adjudicated cardiovascular death or hospitalized HF. RESULTS Participants with a history of HF at baseline (14.4%) were more frequently women, white, and hypertensive and had a history of prior cardiovascular disease (all P<0.001). Greater proportions of these patients were using therapies such as blockers of the renin angiotensin aldosterone system, diuretics, and β-blockers at baseline (all P<0.001). Overall, cardiovascular death or hospitalized HF was reduced in those treated with canagliflozin compared with placebo (16.3 versus 20.8 per 1000 patient-years; hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.67-0.91), as was fatal or hospitalized HF (HR, 0.70; 95% CI, 0.55-0.89) and hospitalized HF alone (HR, 0.67; 95% CI, 0.52-0.87). The benefit on cardiovascular death or hospitalized HF may be greater in patients with a prior history of HF (HR, 0.61; 95% CI, 0.46-0.80) compared with those without HF at baseline (HR, 0.87; 95% CI, 0.72-1.06; P interaction =0.021). The effects of canagliflozin compared with placebo on other cardiovascular outcomes and key safety outcomes were similar in participants with and without HF at baseline (all interaction P values >0.130), except for a possibly reduced absolute rate of events attributable to osmotic diuresis among those with a prior history of HF ( P=0.03). CONCLUSIONS In patients with type 2 diabetes mellitus and an elevated risk of cardiovascular disease, canagliflozin reduced the risk of cardiovascular death or hospitalized HF across a broad range of different patient subgroups. Benefits may be greater in those with a history of HF at baseline. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01032629 and NCT01989754.

中文翻译：

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Canagliflozin和2型糖尿病的心力衰竭。

背景技术Canagliflozin是降低心血管事件风险的钠葡萄糖共转运蛋白2抑制剂。我们报告了在有和没有基线HF史的患者以及其他参与者亚组中，总体上对心力衰竭（HF）和心血管死亡的影响。方法CANVAS计划（Canagliflozin心血管评估研究）招募了10 142名患有2型糖尿病和高心血管风险的参与者。将参与者随机分配到canagliflozin或安慰剂中，平均随访188周。这些分析的主要终点是判定心血管死亡或住院HF。结果基线有心衰史（14.4％）的参与者更常见于女性，白人和高血压，并且有既往心血管疾病史（所有P <0.001）。这些患者中有更大比例使用基线时的肾素血管紧张素醛固酮系统阻滞剂，利尿剂和β受体阻滞剂（所有P <0.001）。总体而言，与安慰剂相比，使用canagliflozin治疗的患者的心血管死亡或住院HF降低（每1000病人年16.3比20.8；危险比[HR]为0.78； 95％置信区间[CI]为0.67-0.91）。致命或住院的HF（HR，0.70; 95％CI，0.55-0.89）和仅住院的HF（HR，0.67; 95％CI，0.52-0.87）。曾有HF史（HR，0.61； 95％CI，0.46-0.80）的患者与基线时无HF的患者（HR，0.87； 95％CI，0.72-）相比，对心血管死亡或住院HF的获益可能更大。 1.06； P相互作用= 0.021）。坎格列净与安慰剂相比，在基线时有无HF的参与者中，其他心血管事件和关键安全性结局的影响相似（所有相互作用P值均> 0.130），除了渗透压利尿事件的绝对事件发生率可能降低之外HF的既往史（P = 0.03）。结论在2型糖尿病和心血管疾病风险升高的患者中，canagliflozin降低了广泛的不同患者亚组的心血管死亡或住院心衰的风险。在基线时有心衰史的患者获益更大。临床试验注册网址：https://www.clinicaltrials.gov。唯一标识符：NCT01032629和NCT01989754。130），除了那些有HF史的患者中由于渗透性利尿导致的绝对事件发生率降低（P = 0.03）。结论在2型糖尿病和心血管疾病风险升高的患者中，canagliflozin降低了广泛的不同患者亚组的心血管死亡或住院心衰的风险。在基线时有心衰史的患者获益更大。临床试验注册网址：https://www.clinicaltrials.gov。唯一标识符：NCT01032629和NCT01989754。130），除了那些有HF史的患者中由于渗透性利尿导致的绝对事件发生率降低（P = 0.03）。结论在2型糖尿病和心血管疾病风险升高的患者中，canagliflozin降低了广泛的不同患者亚组的心血管死亡或住院心衰的风险。在基线时有心衰史的患者获益更大。临床试验注册网址：https://www.clinicaltrials.gov。唯一标识符：NCT01032629和NCT01989754。canagliflozin降低了许多不同患者亚组的心血管死亡或住院HF的风险。在基线时有心衰史的患者获益更大。临床试验注册网址：https://www.clinicaltrials.gov。唯一标识符：NCT01032629和NCT01989754。canagliflozin降低了许多不同患者亚组的心血管死亡或住院HF的风险。在基线时有心衰史的患者获益更大。临床试验注册网址：https://www.clinicaltrials.gov。唯一标识符：NCT01032629和NCT01989754。