1. Randomized Trial of Empagliflozin in Nondiabetic Patients With Heart Failure and Reduced Ejection Fraction.
- Author
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Santos-Gallego, Carlos G., Vargas-Delgado, Ariana P., Requena-Ibanez, Juan Antonio, Garcia-Ropero, Alvaro, Mancini, Donna, Pinney, Sean, Macaluso, Frank, Sartori, Samantha, Roque, Merce, Sabatel-Perez, Fernando, Rodriguez-Cordero, Anderly, Zafar, M. Urooj, Fergus, Icilma, Atallah-Lajam, Farah, Contreras, Johanna P., Varley, Cathleen, Moreno, Pedro R., Abascal, Vivian M., Lala, Anuradha, and Tamler, Ronald
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SODIUM-glucose cotransporter 2 inhibitors , *HEART failure patients , *EMPAGLIFLOZIN , *VENTRICULAR ejection fraction , *EXERCISE tests , *SALT-free diet , *BENZENE , *RESEARCH , *RESEARCH methodology , *GLYCOSIDES , *MEDICAL cooperation , *EVALUATION research , *DIAGNOSTIC imaging , *COMPARATIVE studies , *RANDOMIZED controlled trials , *BLIND experiment , *QUALITY of life , *QUESTIONNAIRES , *STROKE volume (Cardiac output) , *HEART failure - Abstract
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. (Are the "Cardiac Benefits" of Empagliflozin Independent of Its Hypoglycemic Activity? [ATRU-4] [EMPA-TROPISM]; NCT03485222). [ABSTRACT FROM AUTHOR]- Published
- 2021
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