Efficacy And Safety Of Empagliflozin In Hospitalized Heart Failure Patients: Main Results From The EMPULSE Trial

Presented at the American Heart Association’s Scientific Sessions 2021 by: Prof. Adriaan Voors, MD, PhD - Groningen, The Netherlands.

Introduction and methods

Aim of the study

The EMPEROR-reduced and EMPEROR-preserved trials demonstrated that the SGLT2 inhibitor empagliflozin reduces the risk of CV or HF hospitalization in patients with chronic HF. This trial investigated whether empagliflozin is safe and improves clinical outcomes in patients hospitalized for acute HF.

Study design

The EMPULSE trial enrolled a total of 530 patients who were hospitalized with a primary diagnosis of acute HF (de novo or decompensated chronic HF), with or without T2DM and regardless of ejection fraction. Mean age of the patients was 68.5 years, 33.8% were women, 45.3% had T2DM, and 31.9% had LVEF>40%. After clinical stabilization, patients were randomized in a 1:1 ratio to receive empagliflozin 10 mg once daily (n=265) or placebo (n=265) for 90 days.

Outcomes

The primary outcome was clinical benefit, which was defined as a hierarchical composite of time to all-cause death, number of HF events (HFE), time to first HFE and change from baseline in KCCQ-TSS after 90 days of treatment. The primary endpoint was assessed by the win ratio of clinical benefit stratified by HF status.

Main results

• Patients with acute HF who were treated with empagliflozin were 36% more likely to have a clinical benefit, compared to those who received placebo (Stratified win ratio 1.36, 95% CI 1.09-1.68, P=0.0054).
• During follow up, 4.2% of patients in the empagliflozin group died, compared to 8.3% of patients in the placebo group. 10.6% of patients experienced a HF event in the empagliflozin group compared to 14.7% in the placebo group.
• The effect of empagliflozin on the primary endpoint was consistent irrespective of type of HF, presence of absence of T2DM, age, sex, region, baseline NT-proBNP, baseline eGFR, baseline AF and baseline LVEF (all interaction P-values >0.05).
• Empagliflozin-treated patients had a 4.5 point (95%CI 0.3-8.9) greater increase in KCCQ-TSS compared to placebo-treated patients (P=0.0347).
• Patients in the empagliflozin group had a 1.5 kg (95%CI 0.3 to 2.8) greater weight loss compared to patients in the placebo group (P=0.0137).
• Empagliflozin did not significantly reduce the outcome of time to CV death or first HFE compared to placebo(HR 0.69, 95%CI 0.45-1.08, P=0.1021).
• Time to all-cause death or first HFE was significantly reduced by 35% in the empagliflozin group compared to the placebo group (HR 0.65, 95%CI 0.43-0.99, P=0.0423).
• There were no safety concerns associated with empagliflozin treatment this patient population.

Conclusion

Initiation of empagliflozin in patients hospitalized with acute HF was associated with clinical benefits within 90 days of treatment, compared to placebo. Empagliflozin was well tolerated in this patient population and the effects on clinical benefit were consistent across all investigated subgroups.

-Our reporting is based on the information provided at the American Heart Association’s Scientific Sessions 2021-