EMPA-REG OUTCOME: Significant CV benefits with Empagliflozin Evident within Weeks of Treatment Initiation

6 Aug, 21

Introduction

The EMPA-REG OUTCOME trial has already demonstrated that in patients with type-2 diabetes mellitus (T2DM) and established atherosclerotic cardiovascular disease (ASCVD), empagliflozin as compared with placebo, reduced the risk of hospitalization for heart failure (HHF) by 35%, CV death/HHF by 34%, and CV death by 38% at a very early stage.

Aim

To determine the time-point after randomization at which these significant benefits of empagliflozin became evident.

Patient Profile

T2DM patients with glycosylated hemoglobin (HbA1c) 7.0%-9.0%, if drug na?ve and HBA1c 7.0%-10.0% if already on stable glucose-lowering therapy (n=7020)
All the study subjects had established ASCVD and estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73m²

Methods

Study Design

A post hoc analysis of the EMPA-REG OUTCOME trial
EMPA-REG OUTCOME was a randomized, double-blind, multi-center clinical trial conducted across Europe, North America and Asia

Treatment Strategy

Patients were randomized to receive empagliflozin 10 mg (n=2345), empagliflozin 25 mg (n=2342) or placebo (n=2333), in addition to the standard of care.

Outcomes

To track time trajectories for the effect of pooled empagliflozin doses vs. placebo on HHF, CV death/HHF, and CV death based on hazard ratios (HR)

Results

Mean age of the study population was 63.1 years, and 72% of them were males.
A statistically beneficial effect of empagliflozin on CV death (72% risk reduction) was first observed on day 59 [HR; 0.28, 95% confidence interval (CI); 0.08-0.96, P = 0.0424] and was generally sustained throughout the trial (overall HR; 0.62, 95% CI; 0.49-0.77, P <0.0001).
A statistically significant 90% risk reduction for HHF with empagliflozin was first evident on day 17 (HR; 0.10, 95% CI; 0.01-0.87, P = 0.0372) and was sustained throughout the study (overall HR; 0.65, 95% CI; 0.50-0.85, P = 0.0017).
With regards to the composite outcome of CV death or HHF, a statistically significant risk reduction of 72% with empagliflozin was first evident on day 27 (HR; 0.28, 95% CI; 0.08-0.97, P = 0.0445) and was sustained throughout follow-up (overall HR; 0.66, 95% CI; 0.55-0.79, P < 0.0001).

Conclusions

This post hoc analysis of the EMPA-REG OUTCOME trial demonstrated that the clinically and statistically significant benefits of empagliflozin in terms of reduced risk of HHF, CV death/HHF, and CV death were evident within weeks of the treatment initiation.
These early benefits were sustained over a long-term. The earliest benefit appeared to be for the reduced risk of HHF.

ESC Heart Fail. Jun 16; 2021 (Published Ahead of Print); doi:10.1002/ehf2.13374.