TY - JOUR
T1 - Randomized Trial of Empagliflozin in Nondiabetic Patients With Heart Failure and Reduced Ejection Fraction
AU - EMPA-TROPISM (ATRU-4) Investigators
AU - Santos-Gallego, Carlos G.
AU - Vargas-Delgado, Ariana P.
AU - Requena-Ibanez, Juan Antonio
AU - Garcia-Ropero, Alvaro
AU - Mancini, Donna
AU - Pinney, Sean
AU - Macaluso, Frank
AU - Sartori, Samantha
AU - Roque, Merce
AU - Sabatel-Perez, Fernando
AU - Rodriguez-Cordero, Anderly
AU - Zafar, M. Urooj
AU - Fergus, Icilma
AU - Atallah-Lajam, Farah
AU - Contreras, Johanna P.
AU - Varley, Cathleen
AU - Moreno, Pedro R.
AU - Abascal, Vivian M.
AU - Lala, Anuradha
AU - Tamler, Ronald
AU - Sanz, Javier
AU - Fuster, Valentin
AU - Badimon, Juan J.
N1 - Publisher Copyright:
© 2021 American College of Cardiology Foundation
PY - 2021/1/26
Y1 - 2021/1/26
N2 - Background: Large clinical trials established the benefits of sodium-glucose cotransporter 2 inhibitors in patients with diabetes and with heart failure with reduced ejection fraction (HFrEF). The early and significant improvement in clinical outcomes is likely explained by effects beyond a reduction in hyperglycemia. Objectives: The purpose of this study was to assess the effect of empagliflozin on left ventricular (LV) function and volumes, functional capacity, and quality of life (QoL) in nondiabetic HFrEF patients. Methods: In this double-blind, placebo-controlled trial, nondiabetic HFrEF patients (n = 84) were randomized to empagliflozin 10 mg daily or placebo for 6 months. The primary endpoint was change in LV end-diastolic and -systolic volume assessed by cardiac magnetic resonance. Secondary endpoints included changes in LV mass, LV ejection fraction, peak oxygen consumption in the cardiopulmonary exercise test, 6-min walk test, and quality of life. Results: Empagliflozin was associated with a significant reduction of LV end-diastolic volume (−25.1 ± 26.0 ml vs. −1.5 ± 25.4 ml for empagliflozin vs. placebo, respectively; p < 0.001) and LV end-systolic volume (−26.6 ± 20.5 ml vs. −0.5 ± 21.9 ml for empagliflozin vs. placebo; p < 0.001). Empagliflozin was associated with reductions in LV mass (−17.8 ± 31.9 g vs. 4.1 ± 13.4 g, for empagliflozin vs. placebo, respectively; p < 0.001) and LV sphericity, and improvements in LV ejection fraction (6.0 ± 4.2 vs. −0.1 ± 3.9; p < 0.001). Patients who received empagliflozin had significant improvements in peak O2 consumption (1.1 ± 2.6 ml/min/kg vs. −0.5 ± 1.9 ml/min/kg for empagliflozin vs. placebo, respectively; p = 0.017), oxygen uptake efficiency slope (111 ± 267 vs. −145 ± 318; p < 0.001), as well as in 6-min walk test (81 ± 64 m vs. −35 ± 68 m; p < 0.001) and quality of life (Kansas City Cardiomyopathy Questionnaire-12: 21 ± 18 vs. 2 ± 15; p < 0.001). Conclusions: Empagliflozin administration to nondiabetic HFrEF patients significantly improves LV volumes, LV mass, LV systolic function, functional capacity, and quality of life when compared with placebo. Our observations strongly support a role for sodium-glucose cotransporter 2 inhibitors in the treatment of HFrEF patients independently of their glycemic status.
AB - Background: Large clinical trials established the benefits of sodium-glucose cotransporter 2 inhibitors in patients with diabetes and with heart failure with reduced ejection fraction (HFrEF). The early and significant improvement in clinical outcomes is likely explained by effects beyond a reduction in hyperglycemia. Objectives: The purpose of this study was to assess the effect of empagliflozin on left ventricular (LV) function and volumes, functional capacity, and quality of life (QoL) in nondiabetic HFrEF patients. Methods: In this double-blind, placebo-controlled trial, nondiabetic HFrEF patients (n = 84) were randomized to empagliflozin 10 mg daily or placebo for 6 months. The primary endpoint was change in LV end-diastolic and -systolic volume assessed by cardiac magnetic resonance. Secondary endpoints included changes in LV mass, LV ejection fraction, peak oxygen consumption in the cardiopulmonary exercise test, 6-min walk test, and quality of life. Results: Empagliflozin was associated with a significant reduction of LV end-diastolic volume (−25.1 ± 26.0 ml vs. −1.5 ± 25.4 ml for empagliflozin vs. placebo, respectively; p < 0.001) and LV end-systolic volume (−26.6 ± 20.5 ml vs. −0.5 ± 21.9 ml for empagliflozin vs. placebo; p < 0.001). Empagliflozin was associated with reductions in LV mass (−17.8 ± 31.9 g vs. 4.1 ± 13.4 g, for empagliflozin vs. placebo, respectively; p < 0.001) and LV sphericity, and improvements in LV ejection fraction (6.0 ± 4.2 vs. −0.1 ± 3.9; p < 0.001). Patients who received empagliflozin had significant improvements in peak O2 consumption (1.1 ± 2.6 ml/min/kg vs. −0.5 ± 1.9 ml/min/kg for empagliflozin vs. placebo, respectively; p = 0.017), oxygen uptake efficiency slope (111 ± 267 vs. −145 ± 318; p < 0.001), as well as in 6-min walk test (81 ± 64 m vs. −35 ± 68 m; p < 0.001) and quality of life (Kansas City Cardiomyopathy Questionnaire-12: 21 ± 18 vs. 2 ± 15; p < 0.001). Conclusions: Empagliflozin administration to nondiabetic HFrEF patients significantly improves LV volumes, LV mass, LV systolic function, functional capacity, and quality of life when compared with placebo. Our observations strongly support a role for sodium-glucose cotransporter 2 inhibitors in the treatment of HFrEF patients independently of their glycemic status.
KW - LV remodeling
KW - SGLT2-inhibitors
KW - cardiac magnetic resonance
KW - clinical trial
KW - heart failure
UR - http://www.scopus.com/inward/record.url?scp=85097923016&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2020.11.008
DO - 10.1016/j.jacc.2020.11.008
M3 - Article
C2 - 33197559
AN - SCOPUS:85097923016
SN - 0735-1097
VL - 77
SP - 243
EP - 255
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 3
ER -