Patients who recently suffered from heart failure (HF) hospitalization (HHF) have a high risk of other cardiovascular (CV) events, rehospitalization and mortality, especially in the first 3 months after discharge.¹ Intervention during this vulnerable phase is critical to improving the patient outcomes.¹ Previously, sodium-glucose cotransporter-2 inhibitors (SGLT2is) such as empagliflozin have demonstrated clinical benefits among patients, regardless of the ejection fraction and diabetes status, and may be good candidates to be initiated early for high-risk patients post-discharge to prevent future CV events.¹

To evaluate the benefits of empagliflozin among HF patients, according to the timing of prior HF hospitalization, Dr. João Pedro Ferreira of the Université de Lorraine, Nancy, France, and his colleagues conducted a post hoc and pooled analysis with the EMPEROR-Pooled database.¹ The results were presented at the American College of Cardiology (ACC) Annual Scientific Session 2023/World Congress of Cardiology (WCC).¹

The EMPEROR-Pooled database consisted of data from the multicenter, randomized, parallel-group, placebo-controlled EMPEROR-Reduced and EMPEROR-Preserved trials.¹ This analysis included 9,718 HF patients who were randomized 1:1 to receive empagliflozin or placebo, and were grouped according to the recency of HHF [i.e., none (n=6,270), <3 months (n=1,050), 3-6 months (n=734), 6-12 months (n=736), and >12 months (n=928)].¹ The primary outcome was the composite of the time to first HHF or CV death over a median follow-up of 21 months.¹ Other study endpoints included renal outcomes and safety.¹

The result showed that the relative risk reduction of the first HHF or CV death with empagliflozin was similar across the timing of HHF (p_interaction=0.67).¹ Notably, the benefit with empagliflozin was more pronounced among patients with a recent HHF (i.e., <3 months HHF prior to enrollment).¹ A similar pattern for the first and total HHF with empagliflozin was observed, reducing the risk of the first HHF by 30% (HR=0.70; 95% CI: 0.62-0.78; p_interaction=0.51) and total HHF by 28% (HR=0.72; 95% CI: 0.63-0.82; p_interaction=0.64).¹ Yet, the benefit of empagliflozin on CV and all-cause mortality was not demonstrated.¹

Regarding the renal endpoint defined by the time to first event of sustained estimated glomerular filtration rate (eGFR) reduction >50% from baseline or end-stage renal disease or renal death, empagliflozin showed a significant risk reduction of 76% (95% CI: 0.07-0.84) and 61% (95% CI: 0.16-0.95) for patients with 3-6 months recent HHF and <3 months recent HHF vs. placebo, respectively.¹ Across all the patient subgroups, empagliflozin demonstrated a slower eGFR decline vs. placebo with a mean difference of 1.46ml/min/1.73m² (95% CI: 1.18-1.73; p_interaction=0.98).¹ The rates of adverse events (AEs) leading to treatment discontinuation were comparable between the 2 study arms (OR=1.02; 95% CI: 0.92-1.13).¹

In summary, empagliflozin reduced the composite endpoint of HFF or CV mortality, and the future HF events, regardless of HHF recency.¹ Patients with a recent HHF, particularly <3 months, experienced a larger absolute benefit from empagliflozin.¹ The findings highlighted the importance of initiating empagliflozin among patients hospitalized for HF as early as possible.