Use of ACE inhibitors in Fontan: Rational or irrational?,☆☆

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Abstract

Background

Despite a lack of evidence supporting the use of angiotensin-converting enzyme (ACE) inhibitors in patients with a Fontan circulation, their use is frequent. We decided to identify the rationale for ACE inhibitor therapy in patients within the Australia and New Zealand Fontan Registry.

Methods

All patients in the Registry taking an ACE inhibitor at last follow up were identified, and a review of medical records was undertaken to determine the rationale for treatment initiation and reasons for treatment continuation or dose increase.

Results

In 2015, 36% of the surviving patients in the Registry (462/1268) were taking an ACE inhibitor. Indications for initiation of therapy were ventricular systolic or diastolic dysfunction (29%), atrioventricular valve regurgitation (19%), preservation of normal ventricular function (7%), prolonged effusions at Fontan (6%), hypertension (6%), other (6%) and unknown (2%). No indication was stated in the remaining patients (25%). Those with hypoplastic left heart syndrome were more likely to be on an ACE inhibitor than those with an alternative primary morphology (70% vs 32%; p < 0.001). Only 36% of the patients treated with an ACE inhibitor at last follow up (166/462) had an indication that would generally justify treatment in a two-ventricle circulation.

Conclusion

It is likely that the use of ACE inhibitors in patients with a Fontan circulation is excessive within our region. The coordination of prospective, multicentre studies and initiatives such as the Australia and New Zealand Fontan Registry will facilitate further investigations to guide treatment decisions in the growing Fontan population.

Introduction

We are now facing a growing population of children, adolescents and young adults who have survived a Fontan procedure [1]. There are no current guidelines identifying optimal care in this population. The Australia and New Zealand Fontan Registry was established to identify outcomes after Fontan surgery and to encourage research that would assess treatment strategies aimed at increasing longevity and quality of life in this population [2]. In an earlier report of outcomes from the Registry, we found that 26% of patients were being treated with an angiotensin-converting enzyme (ACE) inhibitor at last follow-up [3]. There is no current evidence supporting the use of ACE inhibitors in patients with a single ventricle circulation; only a few small studies have been performed, none of which have focused on long-term outcomes [4], [5], [6], [7]. We sought to identify the rationale for the use of ACE inhibitors in Fontan patients in Australia and New Zealand and if possible, evaluate the cost and impact of their use.

Section snippets

Methods

The Australia and New Zealand Fontan Registry, created in 2008, is a binational, population-based registry that collects the clinical data of all patients who have undergone a Fontan procedure in either country, as well as those who had their Fontan procedure overseas and are now followed within the region [2]. There were 1444 hospital survivors of a Fontan procedure in Australia and New Zealand between January 1975 and May 2015. During post-discharge follow-up of these patients there were 129

Results

At most recent follow up, 36% of the participants in the Australia and New Zealand Fontan Registry were taking an ACE inhibitor (457/1268) and 0.4% were taking an ARB (5/1268). The characteristics of those who were taking an ACE-inhibitor or ARB, compared to those who were not, are summarized in Table 1.

The most commonly prescribed agent of the two classes was lisinopril (54%, 248/462), followed by enalapril (24%, 111/462), cilazapril (5%, 23/462), perindopril (5%, 21/462), captopril (5%,

Discussion

Despite no proven indications for their use in single ventricle palliation, we have demonstrated that a high proportion of patients with a Fontan circulation are treated with ACE inhibitors in our region.

A limited number of trials have investigated the benefits of ACE inhibitors in the Fontan population, the majority of which were underpowered and focused on short-term outcomes [5], [6], [7], [10], [11]. No study has shown ACE inhibitors to be effective in improving exercise capacity, growth

Conclusion

Despite a paucity of evidence supporting the use of ACE inhibitors in patients with a Fontan circulation, more than a third of the patients within our region are currently taking one of these agents. Only a third of the patients identified had a well-recognised indication for ongoing treatment. A significant proportion of the remaining two thirds appeared to be treated on the assumption that long-term administration of ACE inhibitors would improve long-term outcomes in patients after Fontan

Disclosures

All other authors have nothing to disclose with regard to commercial support.

Conflicts of interest

Yves d'Udekem is consultant for MSD and Actelion. David S Celermajer report consulting fees from Actelion.

Acknowledgements

The authors thank Murdoch Childrens Research Institute for infrastructure support. The authors also acknowledge Fontan Registry management and research assistants for their invaluable support in the creation and maintenance of the Registry, as well as support in data gathering for this paper and to Belinda Bortone for administrative support. The authors acknowledge support provided to the Murdoch Childrens Research Institute by the Victorian Government's Operational Infrastructure Support

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  • Cited by (36)

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      It is possible that there are difference in case mix and/or propensity to prescribe medications between PHN and other centers. In a contemporary study from the Australia/New Zealand Fontan Registry the likelihood of ACEi/ARB prescription (36%) was similar to our study population.10 The similarities with this contemporary cohort could be seen as supporting an era effect, but the Australia/New Zealand Fontan is also an unselected sample of Fontan survivors, so the same issues of case mix and practice variation may apply.

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    All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

    ☆☆

    Acknowledgement of Grant Support: The Australia and New Zealand Fontan Registry is funded by grants from the National Health and Medical Research Council (NHMRC; Project Grants 1012241, 1047923, 1065794). The authors acknowledge support provided to the Murdoch Childrens Research Institute by the Victorian Government's Operational Infrastructure Support Programme. Yves d'Udekem is a NHMRC Clinician Practitioner Fellow (1082186). The Victorian Government's Operational Infrastructure Support Programme supported this research project.

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