Comorbidities and cause-specific outcomes in heart failure across the ejection fraction spectrum: A blueprint for clinical trial design.

Atrial fibrillation Chronic kidney disease Ejection fraction Heart failure Trial design Type 2 diabetes mellitus

Journal

International journal of cardiology
ISSN: 1874-1754
Titre abrégé: Int J Cardiol
Pays: Netherlands
ID NLM: 8200291

Informations de publication

Date de publication:
15 08 2020
Historique:
received: 31 03 2020
revised: 17 04 2020
accepted: 24 04 2020
pubmed: 4 5 2020
medline: 15 5 2021
entrez: 4 5 2020
Statut: ppublish

Résumé

Comorbidities may differently affect treatment response and cause-specific outcomes in heart failure (HF) with preserved (HFpEF) vs. mid-range/mildly-reduced (HFmrEF) vs. reduced (HFrEF) ejection fraction (EF), complicating trial design. In patients with HF, we performed a comprehensive analysis of type 2 diabetes (T2DM), atrial fibrillation (AF) chronic kidney disease (CKD), and cause-specific outcomes. Of 42,583 patients from the Swedish HF registry (23% HFpEF, 21% HFmrEF, 56% HFrEF), 24% had T2DM, 51% CKD, 56% AF, and 8% all three comorbidities. HFpEF had higher prevalence of CKD and AF, HFmrEF had intermediate prevalence of AF, and prevalence of T2DM was similar across the EF spectrum. Patients with T2DM, AF and/or CKD were more likely to have also other comorbidities and more severe HF. Risk of cardiovascular (CV) events was highest in HFrEF vs. HFpEF and HFmrEF; non-CV risk was highest in HFpEF vs. HFmrEF vs. HFrEF. T2DM increased CV and non-CV events similarly but less so in HFpEF. CKD increased CV events somewhat more than non-CV events and less so in HFpEF. AF increased CV events considerably more than non-CV events and more so in HFpEF and HFmrEF. HFpEF is distinguished from HFmrEF and HFrEF by more comorbidities, non-CV events, but lower effect of T2DM and CKD on events. CV events are most frequent in HFrEF. To enrich for CV vs. non-CV events, trialists should not exclude patients with lower EF, AF and/or CKD, who report higher CV risk.

Sections du résumé

BACKGROUND
Comorbidities may differently affect treatment response and cause-specific outcomes in heart failure (HF) with preserved (HFpEF) vs. mid-range/mildly-reduced (HFmrEF) vs. reduced (HFrEF) ejection fraction (EF), complicating trial design. In patients with HF, we performed a comprehensive analysis of type 2 diabetes (T2DM), atrial fibrillation (AF) chronic kidney disease (CKD), and cause-specific outcomes.
METHODS AND RESULTS
Of 42,583 patients from the Swedish HF registry (23% HFpEF, 21% HFmrEF, 56% HFrEF), 24% had T2DM, 51% CKD, 56% AF, and 8% all three comorbidities. HFpEF had higher prevalence of CKD and AF, HFmrEF had intermediate prevalence of AF, and prevalence of T2DM was similar across the EF spectrum. Patients with T2DM, AF and/or CKD were more likely to have also other comorbidities and more severe HF. Risk of cardiovascular (CV) events was highest in HFrEF vs. HFpEF and HFmrEF; non-CV risk was highest in HFpEF vs. HFmrEF vs. HFrEF. T2DM increased CV and non-CV events similarly but less so in HFpEF. CKD increased CV events somewhat more than non-CV events and less so in HFpEF. AF increased CV events considerably more than non-CV events and more so in HFpEF and HFmrEF.
CONCLUSION
HFpEF is distinguished from HFmrEF and HFrEF by more comorbidities, non-CV events, but lower effect of T2DM and CKD on events. CV events are most frequent in HFrEF. To enrich for CV vs. non-CV events, trialists should not exclude patients with lower EF, AF and/or CKD, who report higher CV risk.

Identifiants

pubmed: 32360702
pii: S0167-5273(20)31679-X
doi: 10.1016/j.ijcard.2020.04.068
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

76-82

Informations de copyright

Copyright © 2020 Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest GS reports grants and personal fees from Vifor, non-financial support from Boehringer Ingelheim, personal fees from Societa´ Prodotti Antibiotici, grants from MSD, grants and personal fees from AstraZeneca, personal fees from Roche, personal fees from Servier, grants from Novartis, personal fees from GENESIS, personal fees from Medtronic, personal fees from Cytokinetics, outside the submitted work. LHL reports grants and personal fees from Boehringer Ingelheim, during the conduct of the study; personal fees from Merck, personal fees from Sanofi, grants and personal fees from Vifor-Fresenius, grants and personal fees from AstraZeneca, grants and personal fees from Relypsa, personal fees from Bayer, grants from Boston Scientific, grants and personal fees from Novartis, personal fees from Pharmacosmos, personal fees from Abbott, grants and personal fees from Mundipharma, personal fees from Medscape, outside the submitted work. CS, BS, TT, IL, US, LB, FC, FA: None related with the current study. AM, SFF, MB, KGB and OV are employed by Boehringer Ingelheim.

Auteurs

Gianluigi Savarese (G)

Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: gianluigi.savarese@ki.se.

Camilla Settergren (C)

Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.

Benedikt Schrage (B)

Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.

Tonje Thorvaldsen (T)

Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.

Ida Löfman (I)

Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.

Ulrik Sartipy (U)

Department of Cardiothoracic Surgery, Karolinska University Hospital, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.

Linda Mellbin (L)

Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.

Andrea Meyers (A)

Boehringer Ingelheim Pharmaceuticals, Ridgefield, United States of America.

Soulmaz Fazeli Farsani (SF)

Boehringer Ingelheim International GmbH, Ingelheim Am Rhein, Germany.

Martina Brueckmann (M)

Boehringer Ingelheim International GmbH, Ingelheim Am Rhein, Germany; Faculty of Medicine Mannheim at the University of Heidelberg, Mannheim, Germany.

Kimberly G Brodovicz (KG)

Boehringer Ingelheim Pharmaceuticals, Ridgefield, United States of America.

Ola Vedin (O)

Affiliation is Boehringer Ingelheim AB, Sweden; Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

Folkert W Asselbergs (FW)

Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, United Kingdom; Health Data Research UK and Institute of Health Informatics, University College London, London, United Kingdom.

Ulf Dahlström (U)

Department of Cardiology, Linköping University, Linköping, Sweden; Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.

Francesco Cosentino (F)

Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.

Lars H Lund (LH)

Division of Cardiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.

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