Introduction and methods

Patient-reported outcomes with empagliflozin in the EMPERIAL trials

HFA Discoveries 2020 webinar presented by Prof. JoAnn Lindenfeld (Nashville, US)

SGLT2 inhibitors have been shown to improve symptoms in patients with HFrEF as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ). The effects of empagliflozin in patients with HF, with or without T2DM on patient-reported outcomes and 6-minute walking test distance have been investigated in two EMPERIAL trials.

In the EMPERIAL-reduced (LVEF ≤40%, n=312) and EMPERIAL-preserved (LVEF >40%, n=315) trials, patients were randomized (1:1) to receive either empagliflozin 10 mg qd or placebo for 12 weeks. In the current analyses, KCCQ - Total Symptom Score (KCCQ-TSS) and Chronic Heart Failure Questionnaire-Self-Administered Standardized Format (CHQ-SAS) were used to measure patient-reported outcomes at baseline and week 12. The primary endpoint for both EMPERIAL-reduced and EMPERIAL-preserved was neutral, therefore all results are considered exploratory.

Main results

• In the EMPERIAL-reduced trial, a greater proportion of patients had KCCQ-TTS improvements of ≥5 points and ≥8 points in the empagliflozin group compared to the placebo group at week 12 (≥5 points: 56.7% vs. 45.8%, OR 1.83, 95%CI 1.12-2.98; ≥8 points: 50.3% vs 39.4%, OR 1.66, 95%CI 1.02-2.72). No treatment effect on KCCQ-TSS was observed in the EMPERIAL-preserved trial.
• At 12 weeks, KCCQ-TSS improved by 4.55 points in the empagliflozin group compared to the placebo group (P=0.0083) in the EMPERIAL-reduced trial.
• Using CHQ-SAS, changes in dyspnea and fatigue were observed at week 12 in the EMPERIAL-reduced trial. Dyspnea and fatigue improved in favor of empagliflozin at week 12 (change from baseline vs. placebo 0.24 [95%CI 0.01-0.046], P=0.0423 for dyspnea and 0.20 [95%CI 0.01-0.39], P=0.0380 for fatigue). No treatment effect on CHQ-SAS was observed in EMPERIAL-preserved.
• All KCCQ summary scores (TSS, Clinical summary score [CSS], and overall summary score [OSS])

improved in favor of empagliflozin in the EMPERIAL-reduced trial. This was mostly due to improvements in symptom frequency, symptom burden and social limitations sub-domains.

• Adverse event (AE) rates were similar between treatment groups in both EMPERIAL trials. Serious AEs were also similar between groups in both trials, although there was a trend toward less serious AEs in the empagliflozin groups.

Conclusions

Analyses of HF symptoms measured by KCCQ-TSS suggest a trend towards reductions in HF symptom burden with empagliflozin compared to placebo in patients with HFrEF. A trend towards improvements in burden of fatigue and dyspnea, measured by CHQ-SAS, with empagliflozin was also observed in HFrEF patients. No treatment effects on KCCQ-TSS and CHQ-SAS were observed in patients with HFpEF.

-Our reporting is based on the information provided by the HFA Discoveries webinar -