medwireNews: Adding the sodium-glucose cotransporter (SGLT)2 inhibitor empagliflozin to standard treatment significantly improves left ventricular (LV) remodeling among patients with heart failure and reduced ejection fraction (HFrEF) but without diabetes, shows a randomized controlled trial.
These findings “are another piece in the puzzle of understanding the mechanism of SGLT2 inhibitor action on myocardial and vascular structure and function,” says Lee Goldberg (University of Pennsylvania, Philadelphia, USA) in a comment accompanying the research published in the Journal of the American College of Cardiology.
The EMPA-TROPISM trial included 84 HFrEF patients, none of whom had diabetes, who were all receiving guideline-directed medical treatment. Participants were randomly assigned to receive 6 months of add-on treatment with empagliflozin 10 mg/day or placebo.
Juan Badimon (Icahn School of Medicine at Mount Sinai School of Medicine, New York, USA) and co-investigators report that average LV end-diastolic volume decreased by 25.1 mL from baseline to 6 months in the empagliflozin arm (from 219.8 mL to 194.7 mL), compared with a decrease of just 1.5 mL (from 210.4 mL to 208.9 mL) in the placebo group, a significant difference.
Similarly, participants given empagliflozin experienced a significantly greater decrease in average LV end-systolic volume than those given placebo, at 26.6 mL versus 0.5 mL. Empagliflozin treatment was also associated with a significant decrease in LV mass and sphericity index, and a significant improvement in LV ejection fraction.
These findings indicate that “empagliflozin significantly reverses and ameliorates LV remodeling,” which “is an important factor in reducing mortality and morbidity in patients with heart failure,” say Badimon and team. They note that the beneficial effect on LV remodeling “parallels the improvement in outcomes” seen with SGLT2 inhibitors in the EMPEROR Reduced and DAPA-HF trials.
Goldberg says it is “remarkable” that “positive remodeling was seen in addition to appropriate background neurohormonal blockade,” given that “most of these agents, themselves, promote positive remodeling.” In all, 88% of the EMPA-TROPISM participants were taking background beta blockers, while 42% were on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and 33% were on mineralocorticoid antagonists.
The EMPA-TROPISM investigators also found that participants treated with empagliflozin “exhibited improvement in functional capacity,” as demonstrated by significant improvements in the 6-minute walk test and peak oxygen consumption, as well as in quality of life scores, compared with those given placebo.
They conclude: “Our observations strongly support a role for sodium-glucose cotransporter 2 inhibitors in the treatment of HFrEF patients independently of their glycemic status.”
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J Am Coll Cardiol 2021; 77: 243–255
J Am Coll Cardiol 2021; 77: 256–258