Effect of Dapagliflozin on Heart Failure and Mortality in Type 2 Diabetes Mellitus

被引：548

作者：

Kato, Eri T. ^{[2
]}

Silverman, Michael G. ^{[3
]}

Mosenzon, Ofri ^{[4
]}

Zelniker, Thomas A. ^{[1
]}

Cahn, Avivit ^{[4
]}

Furtado, Remo H. M. ^{[1
]}

Kuder, Julia ^{[1
]}

Murphy, Sabina A. ^{[1
]}

Bhatt, Deepak L. ^{[1
]}

Leiter, Lawrence A. ^{[5
]}

McGuire, Darren K. ^{[6
]}

Wilding, John P. H. ^{[7
]}

Bonaca, Marc P. ^{[8
]}

Ruff, Christian T. ^{[1
]}

Desai, Akshay S. ^{[9
]}

Goto, Shinya ^{[10
]}

Johansson, Peter A. ^{[11
]}

Gause-Nilsson, Ingrid ^{[11
]}

Johanson, Per ^{[11
]}

Langkilde, Anna Maria ^{[11
]}

Raz, Itamar ^{[4
]}

Sabatine, Marc S. ^{[1
]}

Wiviott, Stephen D. ^{[1
]}

机构：

[1] Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, 60 Fenwood Rd,Ste 7022, Boston, MA 02115 USA

[2] Kyoto Univ, Grad Sch Med, Dept Cardiovasc Med, Kyoto, Japan

[3] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA

[4] Hebrew Univ Jerusalem, Fac Med, Hadassah Med Ctr, Diabet Unit,Dept Endocrinol & Metab, Jerusalem, Israel

[5] Univ Toronto, St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON, Canada

[6] Univ Texas Southwestern Med Ctr Dallas, Div Cardiol, Dallas, TX 75390 USA

[7] Univ Liverpool, Inst Ageing & Chron Dis, Liverpool, Merseyside, England

[8] Univ Colorado, CPC Clin Res, Denver, CO 80202 USA

[9] Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA

[10] Tokai Univ, Dept Med Cardiol, Isehara, Kanagawa, Japan

[11] AstraZeneca, Gothenburg, Sweden

来源：

CIRCULATION | 2019年 / 139卷 / 22期

关键词：

diabetes mellitus; sodium-glucose transporter 2 inhibitors; heart failure; mortality; CARDIOVASCULAR EVENTS; OUTCOMES; EMPAGLIFLOZIN; ASSOCIATION; DIAGNOSIS; IMPACT;

D O I：

10.1161/CIRCULATIONAHA.119.040130

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

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.

引用

页码：2528 / 2536

页数：9

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