Efficacy of empagliflozin in heart failure with preserved ejection fraction according to frailty status in EMPEROR‐Preserved

Author:

Coats Andrew J.S.1,Butler Javed23,Tsutsui Hiroyuki4,Doehner Wolfram567,Filippatos Gerasimos8,Ferreira João Pedro91011,Böhm Michael12,Chopra Vijay K.13,Verma Subodh14,Nordaby Matias15,Iwata Tomoko16,Nitta Daisuke17,Ponikowski Piotr18,Zannad Faiez11,Packer Milton1920,Anker Stefan D.2122

Affiliation:

1. Heart Research Institute Sydney Australia

2. Baylor Scott and White Research Institute Dallas TX USA

3. University of Mississippi Medical Center Jackson MS USA

4. School of Medicine and Graduate School International University of Health and Welfare Okawa Japan

5. Berlin Institute of Health Center for Regenerative Therapies (BCRT) Charité Universitätsmedizin Berlin Germany

6. Deutsches Herzzentrum der Charité, Department of Cardiology (Campus Virchow) Charité Universitätsmedizin Berlin Germany

7. German Centre for Cardiovascular Research (DZHK) Partner Site Berlin Charité Universitätsmedizin Berlin Germany

8. National and Kapodistrian University of Athens School of Medicine Athens University Hospital Attikon Athens Greece

9. Cardiovascular R&D Centre—UnIC@RISE, Department of Physiology and Cardiothoracic Surgery Faculty of Medicine of the University of Porto Porto Portugal

10. Department of Internal Medicine Heart Failure Clinic, Centro Hospitalar de Vila Nova de Gaia/Espinho Vila Nova de Gaia Portugal

11. Université de Lorraine, Inserm, Centre d'Investigation Clinique Plurithématique 1433, U1116, CHRU de Nancy, F‐CRIN INI‐CRCT Nancy France

12. Department of Internal Medicine III University Hospital Saarland, Saarland University Homburg Germany

13. Max Super Speciality Hospital, Saket New Delhi India

14. Division of Cardiac Surgery St Michael's Hospital, University of Toronto Toronto ON Canada

15. Boehringer Ingelheim International GmbH Ingelheim Germany

16. Boehringer Ingelheim Pharma GmbH & Co KG Biberach Germany

17. Medicine Division Nippon Boehringer Ingelheim Co. Ltd Tokyo Japan

18. Center for Heart Diseases University Hospital, Wroclaw Medical University Wrocław Poland

19. Baylor Heart and Vascular Institute Baylor University Medical Center Dallas TX USA

20. Imperial College London UK

21. Department of Cardiology (CVK) of German Heart Center Charité; Institute of Health Center for Regenerative Therapies (BCRT), German Centre for Cardiovascular Research (DZHK) partner site Berlin Charité Universitätsmedizin Berlin Germany

22. Institute of Heart Diseases Wroclaw Medical University Wrocław Poland

Abstract

AbstractBackgroundFrailty is a severe, common co‐morbidity associated with heart failure (HF) with preserved ejection fraction (HFpEF). The impact of frailty on HFpEF outcomes may affect treatment choices in HFpEF. The impact of frailty on HFpEF patients and any impact on the clinical benefits of sodium glucose co‐transporter 2 (SGLT2) inhibition in HFpEF have been described in only a limited number of trials. Whether the SGLT2 inhibitor empagliflozin would improve or worsen frailty status when given to HFpEF patients is also not known. The aims of this study were, therefore, to evaluate, in HFpEF patients enrolled in the EMPEROR‐Preserved trial (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction), the impact of frailty on clinical outcomes, and on the effects of empagliflozin, as well as the effect of empagliflozin on frailty status during treatment period.MethodsWe calculated a cumulative deficit‐derived frailty index (FI) using 44 variables including clinical, laboratory and quality of life parameters recorded in EMPEROR‐Preserved. Patients were classified into four groups: non‐frail (FI < 0.21), mild frailty (0.21 to <0.30), moderate frailty (0.30 to <0.40) and severe frailty (≥0.40). Clinical outcomes and health‐related quality of life were evaluated according to baseline FI along with the effect of empagliflozin on chronological changes in FI (at 12, 32 and 52 weeks).ResultsThe patient distribution was 1514 (25.3%), 2100 (35.1%), 1501 (25.1%) and 873 (14.6%) in non‐frail, mild frailty, moderate frailty and severe frailty, respectively. Severe frailty patients tended to be female and have low Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, more co‐morbidities and more polypharmacy. Incidence rates of the primary outcome of cardiovascular death or HF hospitalization increased as frailty worsened (hazard ratio [HR] of each FI category compared with the non‐frail group: 1.10 [95% confidence interval, CI, 0.89–1.35], 2.00 [1.63–2.47] and 2.61 [2.08–3.27] in the mild frailty, moderate frailty and severe frailty groups, respectively; P trend < 0.001). Compared with placebo, empagliflozin reduced the risk for the primary outcome across the four FI categories, HR: 0.59 [95% CI 0.42–0.83], 0.79 [0.61–1.01], 0.77 [0.61–0.96] and 0.90 [0.69–1.16] in non‐frail to severe frailty categories, respectively (P value for trend = 0.097). Empagliflozin also improved other clinical outcomes and KCCQ score across frailty categories. Compared with placebo, empagliflozin‐treated patients had a higher likelihood of being in a lower FI category at Weeks 12, 32 and 52 (P < 0.05), odds ratio: 1.12 [95% CI 1.01–1.24] at Week 12, 1.21 [1.09–1.34] at Week 32 and 1.20 [1.09–1.33] at Week 52.ConclusionsEmpagliflozin improved key efficacy outcomes with a possible diminution of effect in very frail patients. Empagliflozin also improved frailty status during follow‐up.

Publisher

Wiley

Subject

Physiology (medical),Orthopedics and Sports Medicine

Cited by 3 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Targeting obesity for therapeutic intervention in heart failure patients;Expert Review of Cardiovascular Therapy;2024-06-02

2. Sodium–glucose cotransporter 2 inhibitors and skeletal muscle;European Journal of Heart Failure;2024-04

3. Frailty, Sarcopenia, Cachexia, and Malnutrition in Heart Failure;Korean Circulation Journal;2024

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