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. 2021 Mar 31;42(13):1203-1212.
doi: 10.1093/eurheartj/ehaa1007.

Empagliflozin and health-related quality of life outcomes in patients with heart failure with reduced ejection fraction: the EMPEROR-Reduced trial

Javed Butler  1 , Stefan D Anker  2 , Gerasimos Filippatos  3 , Muhammad Shahzeb Khan  1 , João Pedro Ferreira  4 , Stuart J Pocock  5 , Nadia Giannetti  6 , James L Januzzi  7 , Ileana L Piña  8 , Carolyn S P Lam  9 , Piotr Ponikowski  10 , Naveed Sattar  11 , Subodh Verma  12 , Martina Brueckmann  13   14 , Waheed Jamal  13 , Ola Vedin  15 , Barbara Peil  16 , Cordula Zeller  17 , Faiez Zannad  4 , Milton Packer  18   19 ; EMPEROR-Reduced Trial Committees and Investigators
Affiliations

Empagliflozin and health-related quality of life outcomes in patients with heart failure with reduced ejection fraction: the EMPEROR-Reduced trial

Javed Butler et al. Eur Heart J. .

Abstract

Aims: In this secondary analysis of the EMPEROR-Reduced trial, we sought to evaluate whether the benefits of empagliflozin varied by baseline health status and how empagliflozin impacted patient-reported outcomes in patients with heart failure with reduced ejection fraction.

Methods and results: Health status was assessed by the Kansas City Cardiomyopathy Questionnaires-clinical summary score (KCCQ-CSS). The influence of baseline KCCQ-CSS (analyzed by tertiles) on the effect of empagliflozin on major outcomes was examined using Cox proportional hazards models. Responder analyses were performed to assess the odds of improvement and deterioration in KCCQ scores related to treatment with empagliflozin. Empagliflozin reduced the primary outcome of cardiovascular death or heart failure hospitalization regardless of baseline KCCQ-CSS tertiles [hazard ratio (HR) 0.83 (0.68-1.02), HR 0.74 (0.58-0.94), and HR 0.61 (0.46-0.82) for <62.5, 62.6-85.4, and ≥85.4 score tertiles, respectively; P-trend = 0.10]. Empagliflozin improved KCCQ-CSS, total symptom score, and overall summary score at 3, 8, and 12 months. More patients on empagliflozin had ≥5-point [odds ratio (OR) 1.20 (1.05-1.37)], 10-point [OR 1.26 (1.10-1.44)], and 15-point [OR 1.29 (1.12-1.48)] improvement and fewer had ≥5-point [OR 0.75 (0.64-0.87)] deterioration in KCCQ-CSS at 3 months. These benefits were sustained at 8 and 12 months and were similar for other KCCQ domains.

Conclusion: Empagliflozin improved cardiovascular death or heart failure hospitalization risk across the range of baseline health status. Empagliflozin improved health status across various domains, and this benefit was sustained during long-term follow-up.

Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03057977.

Keywords: Empagliflozin; Health status; Heart failure; Quality of life; SGLT2 inhibitors.

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Figures

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Graphical abstract
Figure 1
Figure 1
Effects of empagliflozin vs. placebo on time to first event of cardiovascular death or heart failure hospitalization according to baseline Kansas City Cardiomyopathy Questionnaires-clinical summary score tertile. Cumulative incidence curves for empagliflozin vs. placebo demonstrating time to composite of cardiovascular death or heart failure hospitalization in (A) lowest baseline Kansas City Cardiomyopathy Questionnaires-clinical summary score tertile, (B) middle baseline Kansas City Cardiomyopathy Questionnaires-clinical summary score tertile, and (C) highest baseline Kansas City Cardiomyopathy Questionnaires-clinical summary score tertile. CI, confidence interval; HR, hazard ratio.
Figure 2
Figure 2
Effects of empagliflozin vs. placebo on mean Kansas City Cardiomyopathy Questionnaire scores. Changes in (A) Kansas City Cardiomyopathy Questionnaire-clinical summary score, (B) Kansas City Cardiomyopathy Questionnaire-total symptom score, and (C) Kansas City Cardiomyopathy Questionnaire-overall summary score from baseline to 3, 8, and 12 months for empagliflozin vs. placebo. All observed data were used regardless whether on- or off-treatment. Adj. mean diff., adjusted mean difference; CI, confidence interval; CSS, clinical summary score; KCCQ, Kansas City Cardiomyopathy Questionnaire; OSS, overall summary score; TSS, total symptom score.
Figure 3
Figure 3
Adjusted mean difference in Kansas City Cardiomyopathy Questionnaire-clinical summary score, total symptom score, overall summary score, and sub-domains for empagliflozin vs. placebo at 3, 8, and 12 months. All observed data were used regardless whether on- or off-treatment. CI, confidence interval; KCCQ, Kansas City Cardiomyopathy Questionnaire.
Figure 4
Figure 4
Responder analyses of clinically meaningful improvement and deterioration in Kansas City Cardiomyopathy Questionnaire-clinical summary score, Kansas City Cardiomyopathy Questionnaire-total symptom score, and Kansas City Cardiomyopathy Questionnaire-overall summary score with empagliflozin vs. placebo over time. Odds ratios for ≥5-, ≥10-, and ≥15-point improvement and ≥5-point deterioration with empagliflozin vs. placebo at 3, 8, and 12 months. CI, confidence interval; CSS, clinical summary score; OSS, overall summary score; TSS, total symptom score.
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