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Eur J Heart Fail. 2019 Dec 9. doi: 10.1002/ejhf.1673. [Epub ahead of print]

European Society of Cardiology/Heart Failure Association position paper on the role and safety of new glucose-lowering drugs in patients with heart failure.

Author information

1
Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
2
Serbian Academy of Sciences and Arts, Belgrade, Serbia.
3
Pharmacology, Centre of Clinical and Experimental Medicine, IRCCS San Raffaele Pisana, Rome, Italy.
4
Centre for Heart Diseases, Wrocław Medical University, Wrocław, Poland.
5
University of Cyprus Medical School, Nicosia, Cyprus.
6
Athens University Hospital Attikon, National and Kapodistrian University of Athens, Athens, Greece.
7
Division of Cardiology, Department of Medicine II, Medical University of Vienna, Vienna, Austria.
8
British Heart Foundation, Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
9
Department of Cardiology, Clinical Centre of Serbia, Belgrade, Serbia.
10
Institute of Cardiometabolism and Nutrition (ICAN), Pierre et Marie Curie University, Paris VI, La Pitié-Salpétrière Hospital, Paris, France.
11
Clinic for Endocrinology, Diabetes and Metabolic Disorders, Clinical Centre, Belgrade, Serbia.
12
Department of Cardiology, Faculty of Medicine, Marmara University, Istanbul, Turkey.
13
Cardiology Unit, Department of Medicine, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden.
14
Division of Cardiology, University of Perugia, Perugia, Italy.
15
Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy.
16
Heart Failure Unit, Cardiology, G. da Saliceto Hospital, Piacenza, Italy.
17
University of Medicine Carol Davila, Bucharest, Romania.
18
Emergency Institute for Cardiovascular Diseases, Bucharest, Romania.
19
Department of Medicine, Karolinska Institutet, and Heart and Vascular Theme, Karolinska University Hospital, Stockholm, Sweden.
20
Hannover Medical School, Institute of Molecular and Translational Therapeutic Strategies, Hannover, Germany.
21
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
22
Faculty of Medicine and Life Sciences, BIOMED - Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
23
Department of Cardiology, Ziekenhuis Oost, Genk, Belgium.
24
Regional Cardiology Centre Volgograd, Volgograd State Medical University, Volgograd, Russia.
25
Department of Cardiology, IRCCS San Raffaele Pisana, Rome, Italy.
26
School of Nursing and Midwifery, Queen's University Belfast, Belfast, UK.
27
Department of Cardiology and Angiology, Medical School Hannover, Hannover, Germany.
28
National Heart and Lung Institute, Imperial College London and Royal Brompton Hospital, London, UK.
29
Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
30
Department of Cardiology (CVK), Berlin Institute of Health Center for Regenerative Therapies (BCRT), German Centre for Cardiovascular Research (DZHK) partner site Berlin, Charité Universitätsmedizin Berlin, Berlin, Germany.
31
Department of Medical Sciences, IRCCS San Raffaele Pisana, Rome, Italy.

Abstract

Type 2 diabetes mellitus (T2DM) is common in patients with heart failure (HF) and associated with considerable morbidity and mortality. Significant advances have recently occurred in the treatment of T2DM, with evidence of several new glucose-lowering medications showing either neutral or beneficial cardiovascular effects. However, some of these agents have safety characteristics with strong practical implications in HF [i.e. dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RA), and sodium-glucose co-transporter type 2 (SGLT-2) inhibitors]. Regarding safety of DPP-4 inhibitors, saxagliptin is not recommended in HF because of a greater risk of HF hospitalisation. There is no compelling evidence of excess HF risk with the other DPP-4 inhibitors. GLP-1 RAs have an overall neutral effect on HF outcomes. However, a signal of harm suggested in two small trials of liraglutide in patients with reduced ejection fraction indicates that their role remains to be defined in established HF. SGLT-2 inhibitors (empagliflozin, canagliflozin and dapagliflozin) have shown a consistent reduction in the risk of HF hospitalisation regardless of baseline cardiovascular risk or history of HF. Accordingly, SGLT-2 inhibitors could be recommended to prevent HF hospitalisation in patients with T2DM and established cardiovascular disease or with multiple risk factors. The recently completed trial with dapagliflozin has shown a significant reduction in cardiovascular mortality and HF events in patients with HF and reduced ejection fraction, with or without T2DM. Several ongoing trials will assess whether the results observed with dapagliflozin could be extended to other SGLT-2 inhibitors in the treatment of HF, with either preserved or reduced ejection fraction, regardless of the presence of T2DM. This position paper aims to summarise relevant clinical trial evidence concerning the role and safety of new glucose-lowering therapies in patients with HF.

KEYWORDS:

Cardiovascular risk; Clinical trial; Dipeptidyl peptidase-4 inhibitor; Glucagon-like peptide-1 receptor agonist; Heart failure; Hospitalisation; Sodium-glucose co-transporter type 2 inhibitor; Type 2 diabetes mellitus

PMID:
31816162
DOI:
10.1002/ejhf.1673

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