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Question 1: How safe are ACE inhibitors for heart failure in children?
  1. Marijke van der Meulen1,
  2. Michiel Dalinghaus1,
  3. Michael Burch2,
  4. Andras Szatmari3,
  5. Cristina Castro Diez4,
  6. Feras Khalil4,
  7. Vanessa Swoboda5,
  8. Johannes Breur6,
  9. Milica Bajcetic7,
  10. Ida Jovanovic8,
  11. Florian B Lagler9,
  12. Ingrid Klingmann10,
  13. Stephanie Laeer11,
  14. Saskia N de Wildt12
  1. 1 Department of Pediatric Cardiology, Erasmus MC - Sophia, Rotterdam, The Netherlands
  2. 2 Cardiothoracic Unit, Great Ormond Street Hospital, London, UK
  3. 3 Department of Pediatric Cardiology, Göttsegen Gyorgy Hungarian Institute of Cardiology, Budapest, Hungary
  4. 4 Institute of Clinical Pharmacy and Pharmacotherapy, Heinrich-Heine Universität Düsseldorf, Dusseldorf, Germany
  5. 5 Medical University of Vienna, Vienna, Austria
  6. 6 Department of Pediatric Cardiology, Wilhelmina Children’s Hospital University Medical Center, Utrecht, Utrecht, The Netherlands
  7. 7 Univerzitetska Dečja Klinika, Belgrade, Serbia
  8. 8 Clinical Pharmacology Unit, University Children’s Hospital, Belgrade, Serbia
  9. 9 Paracelsus Medizinische Privatuniversitat, Salzburg, Austria
  10. 10 Pharmaplex bvba, Wezembeek_Oppem, Belgium
  11. 11 Department of Clinical Pharmacy and Pharmacotherapy, Heinrich-Heine-Universität, Düsseldorf, Germany
  12. 12 Department of Pharmacology and Toxicology, Radboud University, Nijmegen, The Netherlands
  1. Correspondence to Dr Michiel Dalinghaus, Paediatric Cardiologist, Erasmus Medical Centre, Sophia Children’s Hospital, Rotterdam, The Netherlands; m.dalinghaus{at}

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A boy aged 1 year, recently diagnosed with dilated cardiomyopathy, has to be treated with enalapril according to the heart failure protocol. The physician wants to know which adverse events she can expect.

Structured clinical question

What are the potential adverse events related to administration of an ACE inhibitor to children with heart failure? What is the prevalence and what are the possible risk factors?


Secondary sources—nil

Electronic databases (PubMed/Medline and Embase) and reference lists of relevant articles were searched with the following strategy: ‘angiotensin-converting enzyme inhibitors’ and ‘heart failure’ and ‘children’. The search yielded 415 individual articles, of which 14 were identified as relevant.


Heart failure is an important cause of morbidity and mortality in children.1

It is commonly treated with ACE inhibitors (ACE-i) despite the lack of evidence on its efficacy.2 This treatment is based on the assumption that blocking of the renin-angiotensin-aldosterone system has a positive effect on morbidity and mortality, as it does in adults with heart failure.3–6 In adults, the most prevalent adverse events (AEs) related to the use of ACER-i are renal failure,7 8 hypotension,9 10 hyperkalemia,9 11 cough12 and angioedema.13 It is assumed that the safety profile of ACE-i differs for children and differs from that for adults, and for children of different ages, as growth and development contribute to variation in the disposition and effect of most drugs administered …

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  • Contributors The article is a critical appraisal of the literature on safety of ACE inhibitors in paediatric heart failure. MdeM, MD, SL and SNdeW had the idea for the article. MdeM and MD performed the literature search. MdeM, MD, SL and SNdeW wrote the article. CC, FK, IJ, MB, FBL, VS, AS, MB, IK and JB critically reviewed the drafts and made suggestions for improvement. SNdeW is the guarantor.

  • Competing interests None declared.

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

  • Data sharing statement No additional data are available.

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