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Original research
Pharmacotherapeutic management of paediatric heart failure and ACE-I use patterns: a European survey
  1. Cristina Castro Díez1,
  2. Feras Khalil1,
  3. Holger Schwender2,
  4. Michiel Dalinghaus3,
  5. Ida Jovanovic4,
  6. Nina Makowski1,
  7. Christoph Male5,
  8. Milica Bajcetic6,7,
  9. Marijke van der Meulen3,
  10. Saskia N de Wildt8,9,
  11. László Ablonczy10,
  12. András Szatmári10,
  13. Ingrid Klingmann11,
  14. Jennifer Walsh12,
  15. Stephanie Läer1
  1. 1 Institute of Clinical Pharmacy and Pharmacotherapy, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
  2. 2 Mathematical Institute, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
  3. 3 Department of Paediatric Cardiology, Erasmus MC Sophia Children’s Hospital, Rotterdam, The Netherlands
  4. 4 Department of Paediatric Cardiology, University Children’s Hospital, Belgrade, Serbia
  5. 5 Department of Paediatric Cardiology, Medical University of Vienna, Vienna, Austria
  6. 6 Department of Clinical Pharmacology, University Children’s Hospital, Belgrade, Serbia
  7. 7 Department of Pharmacology, Clinical Pharmacology and Toxicology, School of Medicine, University of Belgrade, Belgrade, Serbia
  8. 8 Department of Pharmacology and Toxicology, Radboud University, Nijmegen, The Netherlands
  9. 9 Intensive Care and Department of Paediatric Surgery, Erasmus MC Sophia Children’s Hospital, Rotterdam, The Netherlands
  10. 10 Göttsegen György Hungarian Institute of Cardiology, Paediatric Heart Centre, Budapest, Hungary
  11. 11 Pharmaplex bvba, Wezembeek-Oppem, Belgium
  12. 12 Jenny Walsh Consulting Ltd, BioCity Nottingham, UK
  1. Correspondence to Dr Stephanie Läer; stephanie.laeer{at}uni-duesseldorf.de

Abstract

Objective To characterise heart failure (HF) maintenance pharmacotherapy for children across Europe and investigate how angiotensin-converting enzyme inhibitors (ACE-I) are used in this setting.

Methods A Europe-wide web-based survey was conducted between January and May 2015 among European paediatricians dedicated to cardiology.

Results Out of 200-eligible, 100 physicians representing 100 hospitals in 27 European countries participated. All participants reported prescribing ACE-I to treat dilated cardiomyopathy-related HF and 97% in the context of congenital heart defects; 87% for single ventricle physiology. Twenty-six per cent avoid ACE-I in newborns. Captopril was most frequently selected as first-choice for newborns (73%) and infants and toddlers (66%) and enalapril for children (56%) and adolescents (58%). Reported starting and maintenance doses varied widely. Up to 72% of participants follow formal creatinine increase limits for decision-making when up-titrating; however, heterogeneity in the cut-off points selected existed. ACE-I formulations prescribed by 47% of participants are obtained from more than a single source. Regarding symptomatic HF maintenance therapy, 25 different initial drug combinations were reported, although 79% select a regimen that includes ACE-I and diuretic (thiazide and/or loop), 61% ACE-I and aldosterone antagonist; 44% start with beta-blocker, 52% use beta-blockers as an add-on drug. Of the 89 participants that prescribe pharmacotherapy to asymptomatic patients, 40% do not use ACE-I monotherapy or ACE-I-beta-blocker two-drug only combination.

Conclusions Despite some reluctance to use them in newborns, ACE-I seem key in paediatric HF treatment strategies. Use in single ventricle patients seems frequent, in apparent contradiction with current paediatric evidence. Disparate dosage criteria and potential formulation-induced variability suggest significant differences may exist in the risk-benefit profile children are exposed to. No uniformity seems to exist in the drug regimens in use. The information collected provides relevant insight into real-life clinical practice and may facilitate research to identify the best therapeutic options for HF children.

  • cardiology
  • paediatric practice
  • pharmacology
  • therapeutics

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • Patient consent for publication Not required.

  • Contributors SL conceived the research idea. CCD, SL, IK, AS, LA, MB, AH, MD, SNW, MM, IJ, MB and CM contributed to the conception of the study. CCD, FK and HS contributed to the study design. CCD performed the experimental part. CCD, FK, NM and HS contributed to the analysis of data. CCD, FK, NM, SL, IK, LA, MD, SNW, IJ, MB and CM contributed to the interpretation of the study results. CCD and SL elaborated the study report. CCD drafted the manuscript. FK, HS, MD, IJ, SNW, IK, CM, JW and SL critically reviewed the manuscript. All authors approved the final version to be submitted for publication.

  • Funding The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement n°602295 (LENA). The aim of the European grant funded ‘Labeling of Enalapril from Neonates to Adolescents’ (LENA) project is to develop a safe, effective and age appropriate formulation of enalapril, for the treatment of heart failure in patients aged from birth to 18 years (https://www.lena-med.eu).

  • Competing interests All authors report grants from European Union Seventh Framework Programme during the conduct of the study.

  • Ethics approval Ethics Committee of the Heinrich-Heine-University Düsseldorf.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement The data can be open for sharing if required.