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

Abstract

Background: Patients with heart failure with preserved ejection fraction have significant impairment in health-related quality of life. In the EMPEROR-Preserved trial (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction), we evaluated the efficacy of empagliflozin on health-related quality of life in patients with heart failure with preserved ejection fraction and whether the clinical benefit observed with empagliflozin varies according to baseline health status.

Methods: Health-related quality of life was measured with the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline and 12, 32, and 52 weeks. Patients were divided by baseline KCCQ Clinical Summary Score (CSS) tertiles, and the effect of empagliflozin on outcomes was examined. The effect of empagliflozin on KCCQ-CSS, Total Symptom Score, and Overall Summary Score was 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 heart failure hospitalization was consistent across baseline KCCQ-CSS tertiles (hazard ratio, 0.83 [95% CI, 0.69-1.00], 0.70 [95% CI, 0.55-0.88], and 0.82 [95% CI, 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 heart failure 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 Total Symptom Score and Overall Summary Score. At 12 weeks, patients on empagliflozin had higher odds of improvement ≥5 points (odds ratio, 1.23 [95% CI, 1.10-1.37]), ≥10 points (odds ratio, 1.15 [95% CI, 1.03-1.27]), and ≥15 points (odds ratio, 1.13 [95% CI, 1.02-1.26]) and lower odds of deterioration ≥5 points in KCCQ-CSS (odds ratio, 0.85 [95% CI, 0.75-0.97]). A similar pattern was seen at 32 and 52 weeks, and results were consistent for Total Symptom Score and Overall Summary Score.

Conclusions: In patients with heart failure with preserved ejection fraction, empagliflozin reduced the risk for major heart failure outcomes across the range of baseline KCCQ scores. Empagliflozin improved health-related quality of life, an effect that appeared early and was sustained for at least 1 year. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03057951.

Keywords: empagliflozin; health status; heart failure, diastolic; quality of life.

Figure 1.

Effect of empagliflozin on outcomes by baseline KCCQ tertiles. CSS indicates Clinical Summary Score; KCCQ, Kansas City Cardiomyopathy Questionnaire; OSS, Overall Summary Score; and TSS, total symptom score. *P value from trend test assuming ordering of the KCCQ tertiles

Figure 2.

Effects of empagliflozin versus placebo on mean KCCQ scores. Changes in (A) Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score, (B) Total Symptom Score, and (C) Overall Summary Score from baseline to 12, 32, and 52 weeks for empagliflozin versus placebo. Adj. mean diff indicates adjusted mean difference.

Figure 3.

Adjusted mean difference in KCCQ-CSS, TSS, OSS, and subdomains for empagliflozin versus placebo at 12, 32, and 52 weeks. CSS indicates Clinical Summary Score; empa, empagliflozin; KCCQ, Kansas City Cardiomyopathy Questionnaire; OSS, Overall Summary Score; and TSS, Total Symptom Score.

Figure 4.

Responder analysis for improvement and deterioration across the KCCQ domains. CSS indicates Clinical Summary Score; empa, empagliflozin; KCCQ, Kansas City Cardiomyopathy Questionnaire; OSS, Overall Summary Score; and TSS, total symptom score

Figure 5.

Responder analysis with proportion of responders at 12, 32, and 52 weeks with empagliflozin versus placebo. CSS indicates Clinical Summary Score; OSS, Overall Summary Score; and TSS, Total Symptom Score.