达格列净对 2 型糖尿病心力衰竭和死亡的影响。
Effect of Dapagliflozin on Heart Failure and Mortality in Type 2 Diabetes Mellitus.
机构信息
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Japan (E.T.K.).
Cardiology Division, Massachusetts General Hospital, Boston (M.G.S.).
出版信息
Circulation. 2019 May 28;139(22):2528-2536. doi: 10.1161/CIRCULATIONAHA.119.040130. Epub 2019 Mar 18.
BACKGROUND
In DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the composite end point of cardiovascular death/hospitalization for heart failure (HHF) in a broad population of patients with type 2 diabetes mellitus. However, the impact of baseline left ventricular ejection fraction (EF) on the clinical benefit of sodium-glucose cotransporter 2 inhibition is unknown.
METHODS
In the DECLARE-TIMI 58 trial, baseline heart failure (HF) status was collected from all patients, and EF was collected when available. HF with reduced EF (HFrEF) was defined as EF <45%. Outcomes of interest were the composite of cardiovascular death/HHF, its components, and all-cause mortality.
RESULTS
Of 17 160 patients, 671 (3.9%) had HFrEF, 1316 (7.7%) had HF without known reduced EF, and 15 173 (88.4%) had no history of HF at baseline. Dapagliflozin reduced cardiovascular death/HHF more in patients with HFrEF (hazard ratio [HR], 0.62 [95% CI, 0.45-0.86]) than in those without HFrEF (HR, 0.88 [95% CI, 0.76-1.02]; P for interaction=0.046), in whom the treatment effect of dapagliflozin was similar in those with HF without known reduced EF (HR, 0.88 [95% CI, 0.66-1.17]) and those without HF (HR, 0.88 [95% CI, 0.74-1.03]). Whereas dapagliflozin reduced HHF both in those with (HR, 0.64 [95% CI, 0.43-0.95]) and in those without HFrEF (HR, 0.76 [95% CI, 0.62-0.92]), it reduced cardiovascular death only in patients with HFrEF (HR, 0.55 [95% CI, 0.34-0.90]) but not in those without HFrEF (HR, 1.08 [95% CI, 0.89-1.31]; P for interaction=0.012). Likewise, dapagliflozin reduced all-cause mortality in patients with HFrEF (HR, 0.59 [95% CI, 0.40-0.88;) but not in those without HFrEF (HR, 0.97 [95% CI, 0.86-1.10]; P for interaction=0.016).
CONCLUSIONS
In the first sodium-glucose cotransporter 2 inhibitor cardiovascular outcome trial to evaluate patients with type 2 diabetes mellitus stratified by EF, we found that dapagliflozin reduced HHF in patients with and without HFrEF and reduced cardiovascular death and all-cause mortality in patients with HFrEF.
CLINICAL TRIAL REGISTRATION
URL: https://www.clinicaltrials.gov . Unique identifier: NCT01730534.
背景
在 DECLARE-TIMI 58 研究（达格列净对心血管事件的影响-心肌梗死 58 溶栓治疗）中，钠-葡萄糖共转运蛋白 2 抑制剂达格列净降低了 2 型糖尿病患者的复合终点心血管死亡/心力衰竭（HHF）住院。然而，基线左心室射血分数（EF）对钠-葡萄糖共转运蛋白 2 抑制的临床获益的影响尚不清楚。
方法
在 DECLARE-TIMI 58 试验中，从所有患者中收集了基线心力衰竭（HF）状况，并在有条件时收集了 EF。射血分数降低的心力衰竭（HFrEF）定义为 EF<45%。感兴趣的结局是心血管死亡/HHF 的复合终点，及其组成部分，以及全因死亡率。
结果
在 17160 名患者中，671 名（3.9%）有 HFrEF，1316 名（7.7%）有射血分数不明确的心力衰竭，15173 名（88.4%）基线时无心力衰竭史。与无 HFrEF 患者（HR，0.88[95%CI，0.76-1.02]；P 交互=0.046）相比，达格列净降低 HFrEF 患者的心血管死亡/HHF 更多（HR，0.62[95%CI，0.45-0.86]），而在无 HFrEF 患者中（HR，0.88[95%CI，0.66-1.17]）和无 HF 患者（HR，0.88[95%CI，0.74-1.03]）中，达格列净的治疗效果相似。虽然达格列净降低了 HHF 发生率（HR，0.64[95%CI，0.43-0.95]），但仅在 HFrEF 患者中降低了心血管死亡（HR，0.55[95%CI，0.34-0.90]），而在无 HFrEF 患者中则没有（HR，1.08[95%CI，0.89-1.31]；P 交互=0.012）。同样，达格列净降低了 HFrEF 患者的全因死亡率（HR，0.59[95%CI，0.40-0.88]），但未降低无 HFrEF 患者的全因死亡率（HR，0.97[95%CI，0.86-1.10]；P 交互=0.016）。
结论
在首个评估 2 型糖尿病患者的钠-葡萄糖共转运蛋白 2 抑制剂心血管结局试验中，按 EF 分层，我们发现达格列净降低了 HFrEF 患者和无 HFrEF 患者的 HHF，降低了 HFrEF 患者的心血管死亡和全因死亡率。
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