Favorable LV remodeling may contribute to empagliflozin benefits
medwireNews: The sodium-glucose cotransporter (SGLT)2 inhibitor empagliflozin may reverse adverse left ventricular (LV) remodeling in people who have heart failure with reduced ejection fraction (HFrEF) and type 2 diabetes or prediabetes, shows a randomized trial.
“This may represent a mechanism by which SGLT2 inhibitors reduce HF hospitalizations and cardiovascular death,” write the SUGAR-DM-HF investigators in Circulation.
Of the 105 people recruited to the study, 78% had type 2 diabetes and 22% had prediabetes, while 77% were in New York Heart Association (NYHA) functional class II and 23% were in class III.
The 45 participants who were randomly assigned to take empagliflozin and completed 36 weeks of treatment achieved a significant average 7.9 mL/m2 reduction in the co-primary outcome of LV end-systolic volume indexed to body surface area (BSA).
By contrast, the 50 participants who remained on placebo treatment for the full study period recorded a reduction of just 1.5 mL/m2. The adjusted between-group difference of 6.0 mL/m2 was statistically significant and remained so after additional post-hoc adjustment for potential imbalances between the groups in sex, NYHA class, and history of HF hospitalization.
In addition, the secondary outcome of LV end-diastolic volume indexed to BSA decreased by an average 9.0 mL/m2 in the empagliflozin group, compared with 0.4 mL/m2 in the placebo group, giving a significant adjusted between-group difference of 8.2 mL/m2.
“The magnitude of change in LV volumes observed at 36 weeks with empagliflozin compares favorably with the effects of other beneficial therapies in HFrEF and was incremental to those effects as our patients were comprehensively treated with renin-angiotensin system blockers and beta-blockers,” say Naveed Sattar (University of Glasgow, UK) and study co-authors.
There were no differences between empagliflozin- and placebo-treated participants for the co-primary outcome of LV global longitudinal strain (GLS).
However, the researchers note: “Strain has not been reported in the older trials of LV remodeling, so it is unclear whether LV GLS is expected to change in parallel with LV volumes.”
There were also no changes in HF symptoms, assessed by Kansas City Cardiomyopathy Questionnaire Total Symptom Score, or in functional capacity according to the 6-minute walk test, although Sattar and team note that they “had limited power to show a change in either of these measures.”
The researchers comment that a previous trial of dapagliflozin failed to detect an effect on LV remodeling, but say the trial was smaller than the current one and involved people with less severe HF, resulting “in limited power to detect a difference between treatments.”
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