TY - JOUR

T1 - Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction

AU - McMurray, John J V

AU - Solomon, Scott D

AU - Inzucchi, Silvio E

AU - Køber, Lars

AU - Kosiborod, Mikhail N

AU - Martinez, Felipe A

AU - Ponikowski, Piotr

AU - Sabatine, Marc S

AU - Anand, Inder S

AU - Bělohlávek, Jan

AU - Böhm, Michael

AU - Chiang, Chern-En

AU - Chopra, Vijay K

AU - de Boer, Rudolf A

AU - Desai, Akshay S

AU - Diez, Mirta

AU - Drozdz, Jaroslaw

AU - Dukát, Andrej

AU - Ge, Junbo

AU - Howlett, Jonathan G

AU - Katova, Tzvetana

AU - Kitakaze, Masafumi

AU - Ljungman, Charlotta E A

AU - Merkely, Béla

AU - Nicolau, Jose C

AU - O'Meara, Eileen

AU - Petrie, Mark C

AU - Vinh, Pham N

AU - Schou, Morten

AU - Tereshchenko, Sergey

AU - Verma, Subodh

AU - Held, Claes

AU - DeMets, David L

AU - Docherty, Kieran F

AU - Jhund, Pardeep S

AU - Bengtsson, Olof

AU - Sjöstrand, Mikaela

AU - Langkilde, Anna-Maria

AU - DAPA-HF Trial Committees and Investigators

PY - 2019

Y1 - 2019

N2 - 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. (Funded by AstraZeneca; DAPA-HF ClinicalTrials.gov number, NCT03036124.).

AB - 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. (Funded by AstraZeneca; DAPA-HF ClinicalTrials.gov number, NCT03036124.).

KW - Aged

KW - Benzhydryl Compounds/adverse effects

KW - Cardiovascular Agents/therapeutic use

KW - Cardiovascular Diseases/mortality

KW - Combined Modality Therapy

KW - Diabetes Mellitus, Type 2/blood

KW - Drug Therapy, Combination

KW - Female

KW - Glucosides/adverse effects

KW - Glycated Hemoglobin A/analysis

KW - Heart Failure/complications

KW - Hospitalization

KW - Humans

KW - Kaplan-Meier Estimate

KW - Male

KW - Middle Aged

KW - Sodium-Glucose Transporter 2 Inhibitors/adverse effects

KW - Stroke Volume/drug effects

KW - Ventricular Dysfunction, Left/complications

U2 - 10.1056/NEJMoa1911303

DO - 10.1056/NEJMoa1911303

M3 - Journal article

C2 - 31535829

VL - 381

SP - 1995

EP - 2008

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 21

ER -