Efficacy of Empagliflozin in Patients With Heart Failure Across Kidney Risk Categories

Javed Butler; Milton Packer; Tariq Jamal Siddiqi; Michael Böhm; Martina Brueckmann; James L Januzzi; Subodh Verma; Ingrid Gergei; Tomoko Iwata; Christoph Wanner; João Pedro Ferreira; Stuart J Pocock; Gerasimos Filippatos; Stefan D Anker; Faiez Zannad

doi:10.1016/j.jacc.2023.03.390

Efficacy of Empagliflozin in Patients With Heart Failure Across Kidney Risk Categories

J Am Coll Cardiol. 2023 May 16;81(19):1902-1914. doi: 10.1016/j.jacc.2023.03.390.

Authors

Affiliations

¹ Baylor Scott and White Research Institute, Dallas, Texas, USA; Department of Medicine, University of Mississippi School of Medicine, Jackson, Mississippi, USA. Electronic address: Javed.Butler@bswhealth.org.
² Baylor University Medical Center, Dallas, Texas, USA; Imperial College, London, United Kingdom.
³ Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.
⁴ Department of Internal Medicine III, University Hospital Saarland, Saarland University, Homburg, Saar, Germany.
⁵ Boehringer Ingelheim International GmbH, Ingelheim, Germany; First Department of Medicine, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany.
⁶ Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA.
⁷ Division of Cardiac Surgery, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
⁸ Boehringer Ingelheim International GmbH, Ingelheim, Germany; Fifth Department of Medicine, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany.
⁹ Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
¹⁰ Würzburg University Clinic, Würzburg, Germany.
¹¹ Centre d'Investigations Cliniques Plurithématique 14-33, Inserm U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Université de Lorraine, Nancy, France; Cardiovascular Research and Development Center, Faculty of Medicine of the University of Porto, Porto, Portugal.
¹² Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom.
¹³ National and Kapodistrian University of Athens School of Medicine, Athens University Hospital Attikon, Athens, Greece.
¹⁴ Department of Cardiology (CVK) and Berlin Institute of Health Center for Regenerative Therapies (BCRT), German Centre for Cardiovascular Research (DZHK) partner site Berlin, Germany, Charité Universitätsmedizin Berlin, Berlin, Germany; Institute of Heart Diseases, Wrocław Medical University, Wrocław, Poland.
¹⁵ Centre d'Investigations Cliniques Plurithématique 14-33, Inserm U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Université de Lorraine, Nancy, France.

PMID: 37164523
DOI: 10.1016/j.jacc.2023.03.390

Abstract

Background: Empagliflozin reduces the risk of major heart failure outcomes in heart failure with reduced or preserved ejection fraction.

Objectives: The goal of this study was to evaluate the effect of empagliflozin across the spectrum of chronic kidney disease in a pooled analysis of EMPEROR-Reduced and EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Reduced or Preserved Ejection Fraction, respectively).

Methods: A total of 9,718 patients were grouped into Kidney Disease Improving Global Outcomes (KDIGO) categories based on estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio into low-, moderate-, high-, and very-high-risk categories, comprising 32.0%, 29.1%, 21.9%, and 17.0% of the participants, respectively.

Results: In the placebo arm, when compared with lower risk categories, patients at higher risk experienced a slower rate of decline in eGFR, but a higher risk of a composite kidney event. Empagliflozin reduced the risk of cardiovascular death or heart failure hospitalizations similarly in all KDIGO categories (HR: 0.81; 95% CI: 0.66-1.01 for low-; HR: 0.63; 95% CI: 0.52-0.76 for moderate-; HR: 0.82; 95% CI: 0.68-0.98 for high-; and HR: 0.84; 95% CI: 0.71-1.01 for very-high-risk groups; P trend = 0.30). Empagliflozin reduced the rate of decline in eGFR whether it was estimated by chronic slope, total slope, or unconfounded slope. When compared with the unconfounded slope, the magnitude of the effect on chronic slope was larger, and the effect on total slope was smaller. In EMPEROR-Reduced, patients at lowest risk experienced the largest effect of empagliflozin on eGFR slope; this pattern was not observed in EMPEROR-Preserved.

Conclusions: The benefit of empagliflozin on major heart failure events was not influenced by KDIGO categories. The magnitude of the renal effects of the drug depended on the approach used to calculate eGFR slopes.

Keywords: KDIGO category; SGLT2 inhibitor; cardiovascular disease; chronic kidney disease; congestive heart failure.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Diabetes Mellitus, Type 2* / complications
Diabetes Mellitus, Type 2* / drug therapy
Heart Failure* / chemically induced
Heart Failure* / drug therapy
Heart Failure* / epidemiology
Humans
Kidney
Renal Insufficiency, Chronic* / complications
Renal Insufficiency, Chronic* / drug therapy
Renal Insufficiency, Chronic* / epidemiology
Sodium-Glucose Transporter 2 Inhibitors* / pharmacology
Stroke Volume

Substances

empagliflozin
Sodium-Glucose Transporter 2 Inhibitors