Pharmacotherapeutic management of paediatric heart failure and ACE-I use patterns: a European survey

Abstract

ObjectiveTo characterise heart failure (HF) maintenance pharmacotherapy for children across Europe and investigate how angiotensin-converting enzyme inhibitors (ACE-I) are used in this setting.MethodsA Europe-wide web-based survey was conducted between January and May 2015 among European paediatricians dedicated to cardiology.ResultsOut 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.ConclusionsDespite 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.

Low‐volume LC–MS/MS method for the pharmacokinetic investigation of carvedilol, enalapril and their metabolites in whole blood and plasma: Application to a paediatric clinical trial

“…Further, the simultaneous determination of two drugs, which represent a common treatment choice in paediatric heart failure (single or combined), 3,5 facilitates the reduction of required blood volumes in children, as both drugs and their metabolites can be determined in one sample. A method to determine carvedilol metabolites in the here presented extend by LC–MS/MS was lacking.…”

“…Within 5 years of their diagnosis, 50%–60% of the patients die or require heart transplants 2 . To mitigate symptoms and prevent further heart damage, drugs like the angiotensin‐converting enzyme (ACE) inhibitor enalapril and the β‐blocker carvedilol are used in children alone or in combination 3–5 . Similarly, these drugs have been applied in children with congenital heart disease and systemic ventricular dysfunction 6 .…”

“…Similarly, the evidence for administration of enalapril in paediatric heart failure is limited 8 . Therefore, currently insufficient evidence for a safe and rational pharmacotherapy in this vulnerable paediatric population is available owing to restricted pharmacokinetic data of carvedilol and enalapril for children 5,9,10 …”

238th ENMC International Workshop: Updating management recommendations of cardiac dystrophinopathyHoofddorp, The Netherlands, 30 November - 2 December 2018

“…Sacubitril-valsartan ('Entresto') may be able to improve on the benefits of ACE-inhibitor therapy but this has yet to be tested in DMD [18] . Although there is good rationale for adding prophylactic beta-blocker therapy to an ACE-inhibitor, the evidence for this is less clear [19][20][21] .…”

A word on netting of angiotensin-converting enzyme inhibitor therapy in hypoplastic left heart syndrome following stage-I

“…Acute efficiency may only be based on SaO2 values related to blood pressure amplitude and urine output. Since infants have a low risk of myocardial fibrosis, 26 therapy with angiotensin-converting enzyme inhibitors is therefore not prescribed to prevent cardiac fibrosis, but rather to reduce a possible AV-valve regurgitation 27 or to influence an excessively high SaO2 that will become caused by an unbalanced Qp/Qs and resulting increased Rs. The generalised conclusion by Hansen et al 1 that prescribing angiotensin-converting enzyme inhibitors is still common despite limited evidence of efficacy in the interstage could misinterpret that angiotensin-converting enzyme inhibitor is generally unsuitable for treating infants during the interstage after stage-I Norwood palliation.…”