Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction

被引：5268

作者：

McMurray, J. J. V. ^{[1
]}

Solomon, S. D. ^{[2
]}

Inzucchi, S. E. ^{[5
]}

Kober, L. ^{[6
]}

Kosiborod, M. N. ^{[9
]}

Martinez, F. A. ^{[10
]}

Ponikowski, P. ^{[12
]}

Sabatine, M. S. ^{[3
,4
]}

Anand, I. S. ^{[14
]}

Belohlavek, J. ^{[15
]}

Bohm, M. ^{[8
]}

Chiang, C. -E. ^{[16
,17
]}

Chopra, V. K. ^{[18
]}

de Boer, R. A. ^{[19
,20
]}

Desai, A. S. ^{[2
]}

Diez, M. ^{[11
]}

Drozdz, J. ^{[13
]}

Dukat, A. ^{[21
]}

Ge, J. ^{[22
,23
]}

Howlett, J. G. ^{[24
,25
]}

Katova, T. ^{[28
]}

Kitakaze, M. ^{[29
]}

Ljungman, C. E. A. ^{[30
]}

Merkely, B. ^{[33
]}

Nicolau, J. C. ^{[34
]}

O'Meara, E. ^{[26
]}

Petrie, M. C. ^{[1
]}

Vinh, P. N. ^{[35
]}

Schou, M. ^{[7
]}

Tereshchenko, S. ^{[36
]}

Verma, S. ^{[27
]}

Held, C. ^{[32
]}

DeMets, D. L. ^{[37
]}

Docherty, K. F. ^{[1
]}

Jhund, P. S. ^{[1
]}

Bengtsson, O. ^{[31
]}

Sjostrand, M. ^{[31
]}

Langkilde, A. -M. ^{[31
]}

机构：

[1] Univ Glasgow, BHF Cardiovasc Res Ctr, Glasgow, Lanark, Scotland

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

[3] Brigham & Womens Hosp, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA

[4] Harvard Med Sch, Boston, MA 02115 USA

[5] Yale Univ, Sch Med, Sect Endocrinol, New Haven, CT USA

[6] Copenhagen Univ Hosp, Rigshosp, Copenhagen, Denmark

[7] Gentofte Univ Hosp, Dept Cardiol, Copenhagen, Denmark

[8] Saarland Univ Hosp, Dept Med, Homburg, Germany

[9] Univ Missouri, St Lukes Mid Amer Heart Inst, Kansas City, MO 64110 USA

[10] Natl Univ Cordoba, Cordoba, Argentina

[11] Inst Cardiovasc Buenos Aires, Div Cardiol, Buenos Aires, DF, Argentina

[12] Wroclaw Med Univ, Wroclaw, Poland

[13] Med Univ Lodz, Dept Cardiol, Lodz, Poland

[14] Univ Minnesota, Dept Cardiol, Minneapolis, MN USA

[15] Charles Univ Prague, Gen Teaching Hosp, Dept Internal Med 2, Cardiovasc Med, Prague, Czech Republic

[16] Taipei Vet Gen Hosp, Div Cardiol, Taipei, Taiwan

[17] Natl Yang Ming Univ, Taipei, Taiwan

[18] Medanta, Dept Cardiol, Gurgaon, India

[19] Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands

[20] Univ Groningen, Groningen, Netherlands

[21] Comenius Univ, Dept Internal Med 5, Bratislava, Slovakia

[22] Shanghai Inst Cardiovasc Dis, Dept Cardiol, Shanghai, Peoples R China

[23] Fudan Univ, Zhongshan Hosp, Shanghai, Peoples R China

[24] Univ Calgary, Cumming Sch Med, Calgary, AB, Canada

[25] Univ Calgary, Libin Cardiovasc Inst, Calgary, AB, Canada

[26] Montreal Heart Inst, Dept Cardiol, Montreal, PQ, Canada

[27] Univ Toronto, Div Cardiac Surg, St Michaels Hosp, Toronto, ON, Canada

[28] Natl Cardiol Hosp, Clin Cardiol, Sofia, Bulgaria

[29] Natl Cerebral & Cardiovasc Ctr, Cardiovasc Div Med, Osaka, Japan

[30] Sahlgrens Acad, Dept Mol & Clin Med & Cardiol, Gothenburg, Sweden

[31] AstraZeneca, Gothenburg, Sweden

[32] Uppsala Univ, Uppsala Clin Res Ctr, Dept Med Sci, Cardiol, Uppsala, Sweden

[33] Semmelweis Univ, Heart & Vasc Ctr, Budapest, Hungary

[34] Univ Sao Paolo, Fac Med, Hosp Clin, Sao Paulo, Brazil

[35] Tan Tao Univ, Dept Internal Med, Tan Duc, Vietnam

[36] Natl Med Res Ctr Cardiol, Dept Myocardial Dis & Heart Failure, Moscow, Russia

[37] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53706 USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2019年 / 381卷 / 21期

关键词：

COTRANSPORTER; 2; INHIBITORS; CARDIOVASCULAR OUTCOMES; NEPRILYSIN INHIBITION; EMPAGLIFLOZIN; MECHANISM;

D O I：

10.1056/NEJMoa1911303

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

BACKGROUND In patients with type 2 diabetes, inhibitors of sodium-glucose cotransporter 2 (SGLT2) reduce the risk of a first hospitalization for heart failure, possibly through glucose-independent mechanisms. More data are needed regarding the effects of SGLT2 inhibitors in patients with established heart failure and a reduced ejection fraction, regardless of the presence or absence of type 2 diabetes. METHODS In this phase 3, placebo-controlled trial, we randomly assigned 4744 patients with New York Heart Association class II, III, or IV heart failure and an ejection fraction of 40% or less to receive either dapagliflozin (at a dose of 10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of worsening heart failure (hospitalization or an urgent visit resulting in intravenous therapy for heart failure) or cardiovascular death. RESULTS Over a median of 18.2 months, the primary outcome occurred in 386 of 2373 patients (16.3%) in the dapagliflozin group and in 502 of 2371 patients (21.2%) in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.65 to 0.85; P<0.001). A first worsening heart failure event occurred in 237 patients (10.0%) in the dapagliflozin group and in 326 patients (13.7%) in the placebo group (hazard ratio, 0.70; 95% CI, 0.59 to 0.83). Death from cardiovascular causes occurred in 227 patients (9.6%) in the dapagliflozin group and in 273 patients (11.5%) in the placebo group (hazard ratio, 0.82; 95% CI, 0.69 to 0.98); 276 patients (11.6%) and 329 patients (13.9%), respectively, died from any cause (hazard ratio, 0.83; 95% CI, 0.71 to 0.97). Findings in patients with diabetes were similar to those in patients without diabetes. The frequency of adverse events related to volume depletion, renal dysfunction, and hypoglycemia did not differ between treatment groups. CONCLUSIONS Among patients with heart failure and a reduced ejection fraction, the risk of worsening heart failure or death from cardiovascular causes was lower among those who received dapagliflozin than among those who received placebo, regardless of the presence or absence of diabetes.

引用

页码：1995 / 2008

页数：14

共 20 条

[1]

Effects of SGLT2 inhibitors on systemic and tissue low-grade inflammation: The potential contribution to diabetes complications and cardiovascular disease [J].