Empagliflozin improves LV function, quality of life in HFrEF without diabetes
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Empagliflozin, an SGLT2 inhibitor, improved left ventricular function and quality of life in patients with HF with reduced ejection fraction and without diabetes, according to findings from the EMPA-TROPISM trial.
“This is the first study demonstrating that empagliflozin ameliorates LV remodeling in nondiabetic HF patients,” Carlos G. Santos-Gallego, MD, postdoctoral fellow in cardiology at the Icahn School of Medicine at Mount Sinai and Mount Sinai Hospital, and colleagues wrote in the Journal of the American College of Cardiology. The findings were also presented at the virtual American Heart Association Scientific Sessions.
“Of utmost importance, empagliflozin-treated patients exhibited improvement in functional capacity and increase in quality of life compared with the placebo arm,” the researchers wrote. “Our observations suggest that SGLT2 inhibitors could become a new therapeutic strategy for the treatment of HFrEF patients independently of their diabetic status.”
For this double-blind, placebo-controlled trial, 84 patients with HFrEF without diabetes (mean age, 62 years; 36% women; 19% Black) were randomly assigned to daily empagliflozin 10 mg (Jardiance, Boehringer Ingelheim/Eli Lilly) or placebo for 6 months to evaluate the effect of empagliflozin on LV function and quality of life. The primary endpoint was change in LV end-diastolic volume and LV end-systolic volume assessed with cardiac MRI. Secondary endpoints were changes in LV mass, LV ejection fraction, peak oxygen consumption in the cardiopulmonary exercise test, the 6-minute walk test and quality of life.
Improvement in LV remodeling
Researchers found that empagliflozin reduced LV end-diastolic volume (25.1 mL vs. 1.5 mL; P < .001) and LV end-systolic volume (26.6 mL vs. 0.5 mL; P < .001) compared with placebo.
Empagliflozin was also associated with reductions in LV mass (17.8 g vs. 4.1 g; P < .001) and improved LVEF (6% vs. 0.1%; P < .001) compared with the placebo group.
“An important observation is the short follow-up needed in EMPA-TROPISM (6 months) to detect significant improvements associated with SGLT2 inhibitors,” the researchers wrote. “This observation coincides with the early separation of the event curves observed in large trials.”
Moreover, those who received empagliflozin experienced better peak oxygen consumption in the cardiopulmonary exercise test (1.1 mL/min/kg vs. 0.5 mL/min/kg; P = .017), improvement in the 6-minute walk test (81 m vs. 35 m; P < .001) and better quality of life as measured by the Kansas City Cardiomyopathy Questionnaire-12 (21 vs. 2; P < .001) compared with the placebo group.
New therapeutic targets
“Ventricular remodeling is an intermediate marker on the path to understanding the true mechanism of action or perhaps actions of the SGLT2 inhibitors on improving heart failure,” Lee R. Goldberg, MD, MPH, FACC, FAHA, professor of medicine at the Hospital of the University of Pennsylvania, wrote in a related editorial. “As this field continues to develop, new therapeutic targets will be identified and more specific and potentially safer agents may be developed. Specific genetic or metabolomic differences between people may allow for a personalized approach to selecting effective pharmacological agents customized to the individual. Thus, demonstrating structural improvement in the ventricle is another step toward unraveling pathways to improve or prevent heart failure.”
References:
- Goldberg LR. J Am Coll Cardiol. 2021;doi:10.1016/j.jacc.2020.11.029.
- Santos-Gallego CG, et al. J Am Coll Cardiol. 2021;doi:10.1016/j.jacc.2020.11.008.
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Badimon J, et al. Featured Science: SGLT2i for nondiabetic indications: Updates from mega-trials and mechanistic insights. Presented at: American Heart Association Scientific Sessions; Nov. 13-17, 2020 (virtual meeting).
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