Empagliflozin, Health Status, and Quality of Life in Patients with Heart Failure and Preserved Ejection Fraction: The EMPEROR-Preserved Trial

Circulation. 2021 Nov 15. doi: 10.1161/CIRCULATIONAHA.121.057812. Online ahead of print.

Abstract

Background: Patients with heart failure and preserved ejection fraction (HFpEF) have significant impairment in health-related quality of life (HRQoL). In EMPEROR-Preserved, we evaluated the efficacy of empagliflozin on HRQoL in patients with HFpEF and whether the clinical benefit observed with empagliflozin varies according to baseline health status. Methods: HRQoL was measured using the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline, 12, 32 and 52 weeks. Patients were divided by baseline KCCQ Clinical Summary Score (CSS) tertiles and the effect of empagliflozin on outcomes were examined. The effect of empagliflozin on KCCQ-CSS, Total Symptom Score (TSS) and Overall Summary Score (OSS) were evaluated. Responder analyses were performed to compare the odds of improvement and deterioration in KCCQ related to treatment with empagliflozin. Results: The effect of empagliflozin on reducing the risk of time to cardiovascular death or HF hospitalization was consistent across baseline KCCQ-CSS tertiles (HR 0.83 [0.69-1.00], HR 0.70 [0.55-0.88] and HR 0.82 [0.62-1.08] for scores <62.5, 62.5-83.3 and ≥83.3, respectively; P trend=0.77). Similar results were seen for total HF hospitalizations. Patients treated with empagliflozin had significant improvement in KCCQ-CSS versus placebo (+1.03, +1.24 and +1.50 at 12, 32 and 52 weeks, respectively P<0.01); similar results were seen for TSS and OSS. At 12 weeks, patients on empagliflozin had higher odds of improvement ≥5 points (OR 1.23; 95%CI 1.10, 1.37), ≥10 points (1.15; 95%CI 1.03, 1.27), and ≥15 points (1.13; 95%CI 1.02, 1.26) and lower odds of deterioration ≥5 points in KCCQ-CSS (0.85; 95%CI 0.75, 0.97). A similar pattern was seen at 32 and 52 weeks, and results were consistent for TSS and OSS. Conclusions: In patients with HFpEF, empagliflozin reduced the risk for major HF outcomes across the range of baseline KCCQ scores. Empagliflozin improved HRQoL, an effect that appeared early and was sustained for at least one year.