EMPEROR-Reduced Trial: Empagliflozin Use Was Associated With a Better Clinical Outcomes Among Patients With Heart Failure and a Reduced Ejection Fraction

Sahar Memar Montazerin, MD
By Sahar Memar Montazerin, MD on

A recent study by Dr. Milton Packer, published in Circulation, demonstrated that empagliflozin use has been associated with a reduction in the total number of inpatient and outpatient visits in patients with heart failure and a reduced ejection fraction. These benefits were observed within  12-28 days of treatment initiation and were persisted over the duration of the trial.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors use has been associated with a reduction in the hospitalization of patients with heart failure and a reduced ejection fraction in previous clinical trials. However, this event represents only a small fraction of the patient’s quality of life. To maintain the clinical stability of these patients, an intervention should also address other manifestations of heart failure worsening, particularly outpatient events. The EMPEROR-Reduced (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction) trial investigated the impact of empagliflozin, an SGLT2 inhibitor, on clinical stability of patients with heart failure and a reduced ejection fraction.

This randomized, double-blind, parallel-group, placebo-controlled study was performed in 520 centers in 20 countries. The study recruited patients with New York Heart Association (NYHA) functional class II-IV heart failure with a left ventricular ejection fraction of ≤ 40%, who were receiving all the conventional therapy for heart failure. Participants were randomly assigned to receive either placebo or empagliflozin 10 mg daily and followed for a median of 16 months prospectively for the development of prespecified outcomes.

A total of 3,730 individuals were enrolled in the trial with 1,876 patients allocated to receive the placebo and 1,863 patients assigned to receive empagliflozin. Compared with placebo, empagliflozin administration led to a reduction in the composite risk of death and hospitalization for heart failure or outpatient visits requiring intravenous treatment. Empagliflozin administration was associated with a decreased number of hospitalization events including those required intensive care (hazard ratio:0.67; [95% CI:0.50-0.90]; P=0.008). Also, its use was associated with a reduction in hospitalization events that required vasopressor or positive inotropic drug or mechanical or surgical intervention. Patients receiving empagliflozin had 20-40% higher odds of experiencing an improvement in their NYHA functional class, a benefit that was apparent as early as 28 days of empagliflozin initiation. 

The previous report of the study showed the benefits of SGLT-2 inhibitor, empagliflozin, in reducing the risk of cardiovascular death or hospitalization for heart failure. This new report further confirmed the observed benefits were regardless of endpoint definitions. In fact, empagliflozin’s effects on cardiovascular death or all-cause mortality remained clinically meaningful and highly significant regardless of the cause of death and hospitalization.

Finally, the findings of the study should be interpreted in light of its limitations. First, the median duration of follow-up was shorter compared to similar clinical trials. Second, outpatient events were defined by the investigators and were not pre-specified.

The findings of the EMPEROR-Reduced and DAPA-HF trial provide evidence for the use of SGLT2 inhibitors as part of the standard of care for patients with heart failure and a reduced ejection fraction, regardless of their diabetes status.


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