Current and advancing treatments for pulmonary arterial hypertension in childhood

Abstract

Pulmonary arterial hypertension (PAH) is a severe and progressive intrinsic disease of the precapillary lung vasculature. Since the introduction of PAH-targeted drugs, survival of PAH patients seems to have improved. Randomized controlled trials have led to evidence-based guidelines to direct treatment in adults. However, since disease characteristics differ between adults and children, it is hazardous to simply extrapolate these guidelines to children. Moreover, pediatric data on treatment strategies and how to assess treatment response remain virtually absent. Optimal treatment strategies are highly needed to guide therapy and improve survival in children with PAH. This review provides an overview of currently available treatments for PAH and the limited efficacy and safety data in children (with the exclusion of perinatal pulmonary vascular diseases, as persistent pulmonary hypertension of the newborn). We also discuss potential treatment goals and how the available data can be translated into treatment strategies in pediatric PAH.

Keywords::

• goal-oriented treatment
• PAH-targeted drugs
• pediatrics
• pulmonary arterial hypertension
• survival
• treatment goal

Financial & competing interests disclosure

The University Medical Center Groningen has received fees for consultancies of Berger for Actelion, Pfizer, GSK, Lilly, United Therapeutics, Bayer and Novartis and grant support from Actelion and Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Pulmonary arterial hypertension (PAH) is a rare, severe progressive disease with a poor prognosis. Since the introduction of PAH-targeted drugs and the development of evidence-based treatment guidelines, survival in adults with PAH seems to have improved.

• There are important differences in pathophysiology, underlying conditions, clinical presentation and outcome between adult and pediatric PAH; therefore, adult treatment algorithms cannot simply be extrapolated to children.

• The scarce available data suggest comparable beneficial effects and safety of PAH-targeted drugs in pediatric PAH. Although survival in children with PAH also seems to have improved, it remains unsatisfactory.

• Goal-oriented treatment, aiming at predefined improvement of clinical condition, has been recommended in adults with PAH to guide and intensify therapy and this could also be helpful in children. However, it is hampered by the lack of validated treatment goals in pediatric PAH.

• The 5th World Symposium for Pulmonary Hypertension pediatric task force has recommended several variables to serve as treatment goals in children with PAH, including clinical symptoms, WHO functional class, (N-terminal pro-)brain natriuretic peptide, right ventricular imaging and invasive hemodynamics.

• Effort should be put in establishing and validating these variables as potential clinically relevant treatment goals, which will help to guide and intensify therapy and improve the currently unsatisfying outcome in pediatric PAH.

Notes