Effects of empagliflozin on cardiac structure and function in pre-HFpEF: results from the ELIVE Pre-HF trial
B Wong, S Flynn, J Dodd, J Lakhar, L Moore, B Dyer, E Gilroy, J Gallagher, P Salgar, K Mcdonald, M LedwidgeAbstract
Background
Empagliflozin improves outcomes in patients with HFpEF. However it is uncertain whether similar benefits extend to non-diabetic individuals earlier in the HFpEF spectrum, where disease modifying therapies are limited.
Purpose
To assess the impact of empagliflozin 10mg versus usual care on structural and functional cardiac changes assessed by Cardiovascular Magnetic Resonance (CMR) over 24 weeks in those with Stage B HFpEF without diabetes.
Methods
This randomised, open-label, blinded end-point trial enrolled 100 non-diabetic patients with stage B HFpEF. Enrolled patients had at least one cardiovascular risk factor and imaging evidence of diastolic dysfunction with preserved ejection fraction in the absence of symptoms. Patients were randomly assigned to empagliflozin 10mg plus usual care or usual care alone. The primary endpoint was change in Left Atrial Volume Index (LAVi) assessed by CMR over 24 weeks. Secondary endpoints included change in: Left Ventricular Ejection Fraction (LVEF), Left ventricular Mass Index (LVMi), Left Ventricular End Systolic Volume Index (LVESVi), Left Ventricular End Diastolic Volume Index (LVEDVi) and change in Brain Natriuretic Peptide (BNP). Efficacy analyses were conducted according to a pre-specified statistical analysis plan using the full analysis set. Multivariate adjustments for the logistic regression analysis were: age, sex, obesity, hypertension, vascular disease and baseline values. A nominal 2-sided significant threshold of 0.05 was used.
Results
Baseline characteristics are presented in Table 1. The mean age was 70.8 (±7.82) years and 42% of patients were female. Baseline characteristics were similar between groups. Table 2 demonstrates, in those treated with empagliflozin, compared to usual care alone, there were no significant differences over 24 weeks in: LAVimax (-1.94 [±8.54]mL/m2 vs. -1.56 [±8.20] mL/m2, p = 0.974), LVEF 0.89 [±7.71]% vs. 1.39 [±9.61]% p = 0.760, LVMi (-6.01 [±17.94]g/m2 vs. -5.72 [±20.02] g/m2, p = 0.67), LVESVi (2.67 [±11.29] mL/m2 vs. 0.84 [±9.00] mL/m2, p = 0.526), or LVEDVi (-0.73 [±16.6] mL/m2 vs. 0.00[±14.10] mL/m2, p = 0.7614). BNP significantly reduced in those treated with empagliflozin (-3.6 [IQR -17.5;8.0] vs. 4.2 [IQR -4.6;18.0] pmol/mL, p = 0.001).
Conclusion
In patients with Stage B HFpEF without diabetes, treatment with empagliflozin 10 mg over 24 weeks did not lead to significant improvements in cardiac structure or function as assessed by CMR; however, BNP levels showed a significant improvement.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.