Department of Medicine and Health Sciences, Division of Community Medicine, Primary Care, Faculty of Health Sciences, Department of Local Care West, County Council of Ötergötland, Linköping University, Sweden (K.R.).
The George Institute for Global Health (K.R., V.P., B.N.).
Circulation. 2018 Jul 31;138(5):458-468. doi: 10.1161/CIRCULATIONAHA.118.034222.
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.
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.
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).
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.
URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01032629 and NCT01989754.
卡格列净是一种钠-葡萄糖协同转运蛋白 2 抑制剂，可降低心血管事件的风险。我们报告了该药对有和无基线心力衰竭史患者的心力衰竭（HF）和心血管死亡的总体影响，以及其他亚组患者的影响。
CANVAS 计划（卡格列净心血管评估研究）纳入了 10142 名患有 2 型糖尿病和心血管风险较高的患者。参与者被随机分配接受卡格列净或安慰剂治疗，并随访平均 188 周。这些分析的主要终点是经裁决的心血管死亡或住院 HF。
基线时有 HF 病史（14.4%）的患者更常为女性、白人、高血压患者，且有既往心血管疾病史（均 P<0.001）。这些患者中有更大比例的人在基线时使用了肾素-血管紧张素-醛固酮系统阻滞剂、利尿剂和β受体阻滞剂等治疗方法（均 P<0.001）。与安慰剂相比，卡格列净治疗组的心血管死亡或住院 HF 发生率降低（每 1000 患者年 16.3 例 vs. 20.8 例；风险比[HR]，0.78；95%置信区间[CI]，0.67-0.91），致命或住院 HF（HR，0.70；95%CI，0.55-0.89）和单独住院 HF（HR，0.67；95%CI，0.52-0.87）也是如此。与基线时无 HF 病史的患者相比（HR，0.87；95%CI，0.72-1.06；P 交互=0.021），有既往 HF 病史的患者的心血管死亡或住院 HF 获益可能更大（HR，0.61；95%CI，0.46-0.80）。与基线时无 HF 病史的患者相比（所有交互 P 值均>0.130），卡格列净与安慰剂相比在其他心血管结局和关键安全性结局方面的效果在基线时有 HF 病史的患者中相似，除了有既往 HF 病史的患者因渗透性利尿而导致的事件绝对发生率可能降低（P=0.03）。
在患有 2 型糖尿病和心血管疾病风险升高的患者中，卡格列净降低了心血管死亡或住院 HF 的风险，适用于广泛的不同患者亚组。有基线 HF 病史的患者可能获益更大。
网址：https://www.clinicaltrials.gov 。唯一标识符：NCT01032629 和 NCT01989754。
