Michael Böhm1, Javed Butler2, Gerasimos Filippatos3, João Pedro Ferreira4, Stuart J Pocock5, Amr Abdin6, Felix Mahfoud6, Martina Brueckmann7, Nicholas D Gollop8, Tomoko Iwata9, Piotr Ponikowski10, Christoph Wanner11, Faiez Zannad4, Milton Packer12, Stefan D Anker13. 1. Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Saarland University, Homburg/Saar, Germany. Electronic address: michael.boehm@uks.eu. 2. Department of Medicine, University of Mississippi School of Medicine, Jackson, Mississippi, USA. 3. National and Kapodistrian University of Athens School of Medicine, Athens University Hospital Attikon, Athens, Greece. 4. Université de Lorraine, Centre d'Investigation Clinique-Plurithématique Inserm 1433, Centre Hospitalier Regional Universitaire, Nancy Brabois, France; Inserm U1116, CHRU Nancy Brabois, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France. 5. Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom. 6. Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Saarland University, Homburg/Saar, Germany. 7. Boehringer Ingelheim International, Ingelheim, Germany; First Department of Medicine, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany. 8. Boehringer Ingelheim International, Ingelheim, Germany. 9. Boehringer Ingelheim Pharma GmbH and Co KG, Biberach/Riss, Germany. 10. Wroclaw Medical University, Wrocław, Poland. 11. Medizinische Klinik und Poliklinik 1, Schwerpunkt Nephrologie, Universitätsklinikum Würzburg, Würzburg, Germany. 12. Baylor University Medical Center, Dallas, Texas, USA; Imperial College, London, United Kingdom. 13. Department of Cardiology and Berlin Institute of Health Center for Regenerative Therapies, German Centre for Cardiovascular Research partner site Berlin, Charité Universitätsmedizin Berlin, Berlin, Germany.
Abstract
BACKGROUND: Empagliflozin reduces cardiovascular death (CVD) or heart failure (HF) hospitalization (HFH) in patients with HF and preserved ejection fraction. Treatment effects and safety in relation to age have not been studied. OBJECTIVES: The purpose of this study was to evaluate the interplay of age and empagliflozin effects in EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction). METHODS: We grouped patients (n = 5,988) according to their baseline age (<65 years [n = 1,199], 65-74 years [n = 2,214], 75-79 years [n = 1,276], ≥80 years [n = 1,299]). We explored the influence of age on empagliflozin effects on CVD or HFH (primary outcome), total HFH, rate of decline in estimated glomerular filtration rate, health-related quality of life with the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score, and frequency of adverse events. RESULTS: Considering only patients on placebo, the incidence of primary outcomes (P trend = 0.02) and CVD (P trend = 0.003) increased with age. Empagliflozin reduced primary outcomes (P trend = 0.33), first HFH (P trend = 0.22), and first and recurrent HFH (P trend = 0.11) across all age groups with an effect being similar at ≥75 years (P interaction = 0.22) or >80 years (P interaction = 0.51). Empagliflozin improved Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score at week 52 and attenuated the decline of estimated glomerular filtration rate without age interaction (P = 0.48 and P = 0.32, respectively). There were no clinically relevant differences in adverse events between empagliflozin and placebo across the age groups. CONCLUSIONS: Empagliflozin reduced primary outcomes and first and recurrent HFH and improved symptoms across a broad age spectrum. High age was not associated with reduced efficacy or meaningful intolerability. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction [EMPEROR-Preserved]; NCT0305951).
BACKGROUND: Empagliflozin reduces cardiovascular death (CVD) or heart failure (HF) hospitalization (HFH) in patients with HF and preserved ejection fraction. Treatment effects and safety in relation to age have not been studied. OBJECTIVES: The purpose of this study was to evaluate the interplay of age and empagliflozin effects in EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction). METHODS: We grouped patients (n = 5,988) according to their baseline age (<65 years [n = 1,199], 65-74 years [n = 2,214], 75-79 years [n = 1,276], ≥80 years [n = 1,299]). We explored the influence of age on empagliflozin effects on CVD or HFH (primary outcome), total HFH, rate of decline in estimated glomerular filtration rate, health-related quality of life with the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score, and frequency of adverse events. RESULTS: Considering only patients on placebo, the incidence of primary outcomes (P trend = 0.02) and CVD (P trend = 0.003) increased with age. Empagliflozin reduced primary outcomes (P trend = 0.33), first HFH (P trend = 0.22), and first and recurrent HFH (P trend = 0.11) across all age groups with an effect being similar at ≥75 years (P interaction = 0.22) or >80 years (P interaction = 0.51). Empagliflozin improved Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score at week 52 and attenuated the decline of estimated glomerular filtration rate without age interaction (P = 0.48 and P = 0.32, respectively). There were no clinically relevant differences in adverse events between empagliflozin and placebo across the age groups. CONCLUSIONS: Empagliflozin reduced primary outcomes and first and recurrent HFH and improved symptoms across a broad age spectrum. High age was not associated with reduced efficacy or meaningful intolerability. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction [EMPEROR-Preserved]; NCT0305951).