Influence of angiotensin receptor-neprilysin inhibition on the efficacy of Empagliflozin on cardiac structure and function in patients with chronic heart failure and a reduced ejection fraction: The Empire HF trial

Abstract

Study objectiveThe objective was to assess the effect of ongoing angiotensin receptor-neprilysin inhibitor(ARNI) on the effect of the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin on left ventricular (LV) size and function in patients with heart failure and reduced ejection fraction(HFrEF). DesignPost hoc analysis of the Empire HF trial, an investigator-initiated, double-blind, randomized controlled trial. Participants190 patients with HFrEF with New York Heart association class I-III symptoms with an ejection fraction of 40 % or below. Patients were stratified according to ongoing ARNI treatment at baseline. InterventionEmpagliflozin 10 mg daily or placebo for 12 weeks. Echocardiography at baseline and follow-up. Main outcome measuresLeft ventricular end-systolic volume index (LVESVI), end-diastolic volume index (LVEDVI), left atrial volume index (LAVI), left ventricular ejection fraction (LVEF). ResultsA total of 58 patients (31 %) received ARNI at baseline. Compared to with placebo, empagliflozin reduced the LVESVI ([−6.2 (−14.1 to 1.6); p = 0.12] and [−3.3 (−8.2 to 1.6); p = 0.19], interaction P = 0.49), LVEDVI ([−11.2 (−21.2 to −1.2); p = 0.03] and [−2.9 (−8.7 to 2.9); p = 0.32], interaction P = 0.13), and LAVI ([−3.9 (−9.1 to 1.2); p = 0.14] and. [−1.8 (−4.4 to 0.7); p = 0.16], respectively, interaction P = 0.9) in patients treated with and without ARNI at baseline, respectively. No treatment-by-ARNI subgroup interaction were found. Unaffected by baseline ARNI treatment, empagliflozin did not improve LVEF. ConclusionThe effect of empagliflozin on cardiac structure and function compared to placebo was not affected by background treatment with ARNI.