Skip to main content
Erschienen in: Pediatric Cardiology 2/2013

01.02.2013 | Review Article

Evolving Management of Pediatric Pulmonary Arterial Hypertension: Impact of Phosphodiesterase Inhibitors

verfasst von: Andrew James Wardle, Robert M. R. Tulloh

Erschienen in: Pediatric Cardiology | Ausgabe 2/2013

Einloggen, um Zugang zu erhalten

Abstract

The treatment of pulmonary arterial hypertension (PAH) has undergone significant change in recent years, improving both quality of life and survival for patients. One of the principal new agents is sildenafil, a phosphodiesterase-V inhibitor with great PAH efficacy. Its success has led to consideration of other phosphodiesterase inhibitors not yet licensed for pediatric PAH including tadalafil and vardenafil, among others. This article summarizes the evidence base for phosphodiesterase inhibitors used to ameliorate pediatric PAH pathology and associated symptoms. It also analyzes their suitability for contemporary practice with the aim of clarifying and helping to direct regimens that produce improved patient outcomes.
Literatur
1.
Zurück zum Zitat Atz AM, Lefler AK, Fairbrother DL et al (2002) Sildenafil augments the effect of inhaled nitric oxide for postoperative pulmonary hypertensive crises. J Thorac Cardiovasc Surg 124:628–629PubMedCrossRef Atz AM, Lefler AK, Fairbrother DL et al (2002) Sildenafil augments the effect of inhaled nitric oxide for postoperative pulmonary hypertensive crises. J Thorac Cardiovasc Surg 124:628–629PubMedCrossRef
2.
Zurück zum Zitat Badesch DB, Champion HC, Sanchez MA et al (2009) Diagnosis and assessment of pulmonary arterial hypertension. J Am Coll Cardiol 54(Suppl 1):S55–S66PubMedCrossRef Badesch DB, Champion HC, Sanchez MA et al (2009) Diagnosis and assessment of pulmonary arterial hypertension. J Am Coll Cardiol 54(Suppl 1):S55–S66PubMedCrossRef
3.
Zurück zum Zitat Barst RJ, Oudiz RJ, Beardsworth A et al (2011) Pulmonary arterial hypertension and response to tadalafil (PHIRST) study group: tadalafil monotherapy and as add-on to background bosentan in patients with pulmonary arterial hypertension. J Heart Lung Transplant 30:632–643PubMedCrossRef Barst RJ, Oudiz RJ, Beardsworth A et al (2011) Pulmonary arterial hypertension and response to tadalafil (PHIRST) study group: tadalafil monotherapy and as add-on to background bosentan in patients with pulmonary arterial hypertension. J Heart Lung Transplant 30:632–643PubMedCrossRef
4.
Zurück zum Zitat Barst RJ, Dunbar I, Gaitan G et al (2012) A randomised double-blind placebo-controlled dose-ranging study of oral sildenfail citrate in treatment naive children with pulmonary arterial hypertension. Circulation 125:324–334PubMedCrossRef Barst RJ, Dunbar I, Gaitan G et al (2012) A randomised double-blind placebo-controlled dose-ranging study of oral sildenfail citrate in treatment naive children with pulmonary arterial hypertension. Circulation 125:324–334PubMedCrossRef
5.
Zurück zum Zitat Barst RJ, McGoon MD, Elliott CG et al (2012) Childhood pulmonary arterial hypertension: insights from the registry to evaluate early and long-term pulmonary arterial hypertension disease management. Circulation 125:113–122PubMedCrossRef Barst RJ, McGoon MD, Elliott CG et al (2012) Childhood pulmonary arterial hypertension: insights from the registry to evaluate early and long-term pulmonary arterial hypertension disease management. Circulation 125:113–122PubMedCrossRef
6.
Zurück zum Zitat Bassler D, Choong K, McNamara P et al (2006) Neonatal persistent pulmonary hypertension treated with milrinone: four case reports. Biol Neonate 89:1–5PubMedCrossRef Bassler D, Choong K, McNamara P et al (2006) Neonatal persistent pulmonary hypertension treated with milrinone: four case reports. Biol Neonate 89:1–5PubMedCrossRef
7.
Zurück zum Zitat Berger RM, Beghetti M, Humpl T et al (2012) Clinical features of paediatric pulmonary hypertension: a registry study. Lancet 379:537–546PubMedCrossRef Berger RM, Beghetti M, Humpl T et al (2012) Clinical features of paediatric pulmonary hypertension: a registry study. Lancet 379:537–546PubMedCrossRef
8.
Zurück zum Zitat Carroll WD, Dhillon R (2003) Sildenafil as a treatment for pulmonary hypertension. Arch Dis Child 88:827–828PubMedCrossRef Carroll WD, Dhillon R (2003) Sildenafil as a treatment for pulmonary hypertension. Arch Dis Child 88:827–828PubMedCrossRef
9.
Zurück zum Zitat Della Torre F, Della Torre E, Di Berardino F (2005) Sildenafil in pulmonary hypertension. Sarcoidosis Vasc Diffuse Lung Dis 22:78–79PubMed Della Torre F, Della Torre E, Di Berardino F (2005) Sildenafil in pulmonary hypertension. Sarcoidosis Vasc Diffuse Lung Dis 22:78–79PubMed
10.
Zurück zum Zitat Derynck R, Zhang YE (2003) Smad-dependent and Smad-independent pathways in TGF family signalling. Nature 425:577–584PubMedCrossRef Derynck R, Zhang YE (2003) Smad-dependent and Smad-independent pathways in TGF family signalling. Nature 425:577–584PubMedCrossRef
11.
Zurück zum Zitat Fraisse A, Jais X, Schleich JM et al (2010) Characteristics and prospective 2-year follow-up of children with pulmonary arterial hypertension in France. Arch Cardiovasc Dis 103:66–74PubMedCrossRef Fraisse A, Jais X, Schleich JM et al (2010) Characteristics and prospective 2-year follow-up of children with pulmonary arterial hypertension in France. Arch Cardiovasc Dis 103:66–74PubMedCrossRef
12.
Zurück zum Zitat Galie JN, Brundage BH, Ghofrani H et al (2009) Tadalafil therapy for pulmonary arterial hypertension. Pulmonary arterial hypertension and response to tadalafil (PHIRST) study group. Circulation 119:2894–2903PubMedCrossRef Galie JN, Brundage BH, Ghofrani H et al (2009) Tadalafil therapy for pulmonary arterial hypertension. Pulmonary arterial hypertension and response to tadalafil (PHIRST) study group. Circulation 119:2894–2903PubMedCrossRef
13.
Zurück zum Zitat Hawkins A, Langton-Hewer S, Henderson J et al (2011) Management of pulmonary hypertension in down syndrome. Eur J Pediatr 170:915–921PubMedCrossRef Hawkins A, Langton-Hewer S, Henderson J et al (2011) Management of pulmonary hypertension in down syndrome. Eur J Pediatr 170:915–921PubMedCrossRef
14.
Zurück zum Zitat Humpl T, Reyes JT, Holtby H et al (2005) Beneficial effect of oral sildenafil therapy on childhood pulmonary arterial hypertension: twelve-month clinical trial of a single drug, open-label, pilot study. Circulation 111:3274–3280PubMedCrossRef Humpl T, Reyes JT, Holtby H et al (2005) Beneficial effect of oral sildenafil therapy on childhood pulmonary arterial hypertension: twelve-month clinical trial of a single drug, open-label, pilot study. Circulation 111:3274–3280PubMedCrossRef
15.
Zurück zum Zitat Jing ZC, Yu ZX, Shen JY et al (2011) Vardenafil in pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled study. Efficacy and safety of vardenafil in the treatment of pulmonary arterial hypertension (evaluation) study group. Am J Respir Crit Care Med 183:1723–1729PubMedCrossRef Jing ZC, Yu ZX, Shen JY et al (2011) Vardenafil in pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled study. Efficacy and safety of vardenafil in the treatment of pulmonary arterial hypertension (evaluation) study group. Am J Respir Crit Care Med 183:1723–1729PubMedCrossRef
16.
Zurück zum Zitat Karasu-Minareci E, Ozbudak I, Ozbillim G, et al (2012) Acute effects of vardenafil on pulmonary artery responsiveness in pulmonary hypertension. Sci World J 2012. doi:10.1100/2012/718279 Karasu-Minareci E, Ozbudak I, Ozbillim G, et al (2012) Acute effects of vardenafil on pulmonary artery responsiveness in pulmonary hypertension. Sci World J 2012. doi:10.​1100/​2012/​718279
17.
Zurück zum Zitat Karatza AA, Bush A, Magee AG (2005) Safety with pulmonary hypertension. Int J Cardiol 100:267–273PubMedCrossRef Karatza AA, Bush A, Magee AG (2005) Safety with pulmonary hypertension. Int J Cardiol 100:267–273PubMedCrossRef
18.
Zurück zum Zitat Lowe G, Costabile R (2012) 10-year analysis of adverse event reports to the food and drug administration for phosphodiesterase type-5 inhibitors. J Sex Med 9:265–270PubMedCrossRef Lowe G, Costabile R (2012) 10-year analysis of adverse event reports to the food and drug administration for phosphodiesterase type-5 inhibitors. J Sex Med 9:265–270PubMedCrossRef
19.
Zurück zum Zitat Moledina S, Hislop AA, Foster H et al (2010) Childhood idiopathic pulmonary arterial hypertension: a national cohort study. Heart 96:1401–1406PubMedCrossRef Moledina S, Hislop AA, Foster H et al (2010) Childhood idiopathic pulmonary arterial hypertension: a national cohort study. Heart 96:1401–1406PubMedCrossRef
20.
Zurück zum Zitat Namachivayam P, Theilen U, Butt WW et al (2006) Sildenafil prevents rebound pulmonary hypertension after withdrawal of nitric oxide in children. Am J Respir Crit Care Med 174:1042–1047PubMedCrossRef Namachivayam P, Theilen U, Butt WW et al (2006) Sildenafil prevents rebound pulmonary hypertension after withdrawal of nitric oxide in children. Am J Respir Crit Care Med 174:1042–1047PubMedCrossRef
21.
Zurück zum Zitat Simmoneau G, Robbins IM, Beghetti M et al (2009) Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 54:S43–S54CrossRef Simmoneau G, Robbins IM, Beghetti M et al (2009) Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 54:S43–S54CrossRef
22.
Zurück zum Zitat Simonneau G, Rubin LJ, Galie N et al (2008) Addition of sildenafil to long-term intravenous epoprostenol therapy in patients with pulmonary arterial hypertension: a randomized trial. Ann Intern Med 149:521–530PubMed Simonneau G, Rubin LJ, Galie N et al (2008) Addition of sildenafil to long-term intravenous epoprostenol therapy in patients with pulmonary arterial hypertension: a randomized trial. Ann Intern Med 149:521–530PubMed
23.
Zurück zum Zitat Spring RM, Ulrich S, Huber LC et al (2008) Sildenafil for pulmonary hypertension: dose-dependent improvement in exercise performance. Pulm Pharmacol Ther 21:516–521PubMedCrossRef Spring RM, Ulrich S, Huber LC et al (2008) Sildenafil for pulmonary hypertension: dose-dependent improvement in exercise performance. Pulm Pharmacol Ther 21:516–521PubMedCrossRef
24.
Zurück zum Zitat Sun X, Li Z, Liu Y et al (2010) Inhibition of cGMP phosphodiesterase 5 suppresses matrix metalloproteinase-2 production in pulmonary artery smooth muscle cells. Clin Exp Pharmacol Physiol 37:362–367PubMedCrossRef Sun X, Li Z, Liu Y et al (2010) Inhibition of cGMP phosphodiesterase 5 suppresses matrix metalloproteinase-2 production in pulmonary artery smooth muscle cells. Clin Exp Pharmacol Physiol 37:362–367PubMedCrossRef
25.
Zurück zum Zitat Takatsuki S, Calderbank M, Ivy DD (2012) Initial experience with tadalfil in pediatric pulmonary arterial hypertension. Pediatr Cardiol 33:683–688PubMedCrossRef Takatsuki S, Calderbank M, Ivy DD (2012) Initial experience with tadalfil in pediatric pulmonary arterial hypertension. Pediatr Cardiol 33:683–688PubMedCrossRef
26.
Zurück zum Zitat Torres F, Gupta H, Soto F, et al (2011) Safety and efficacy of bosentan in combination with sildenafil in pulmonary arterial hypertension: the COMPASS-3 Study (abstract). In: ERS Annual Congress 2011 Torres F, Gupta H, Soto F, et al (2011) Safety and efficacy of bosentan in combination with sildenafil in pulmonary arterial hypertension: the COMPASS-3 Study (abstract). In: ERS Annual Congress 2011
27.
Zurück zum Zitat Tudor A, Muşat A, Bari M et al (2005) Observations on peripheral microcirculation in young hypertensive patients. Rom J Intern Med 43:73–78PubMed Tudor A, Muşat A, Bari M et al (2005) Observations on peripheral microcirculation in young hypertensive patients. Rom J Intern Med 43:73–78PubMed
29.
Zurück zum Zitat Wirostko B, Trssler C, Hwang L et al (2012) Ocular safety of sildenafil citrate when administered chronically for pulmonary arterial hypertension: results from phase III, randomised, double-masked, placebo-controlled trial and open label extension. BMJ 344:e554PubMedCrossRef Wirostko B, Trssler C, Hwang L et al (2012) Ocular safety of sildenafil citrate when administered chronically for pulmonary arterial hypertension: results from phase III, randomised, double-masked, placebo-controlled trial and open label extension. BMJ 344:e554PubMedCrossRef
30.
Zurück zum Zitat Wrishko RE, Dingemanse J, Yu A et al (2008) Pharmacokinetic interaction between tadalafil and bosentan in healthy male subjects. J Clin Pharmacol 48:610–618PubMedCrossRef Wrishko RE, Dingemanse J, Yu A et al (2008) Pharmacokinetic interaction between tadalafil and bosentan in healthy male subjects. J Clin Pharmacol 48:610–618PubMedCrossRef
Metadaten
Titel
Evolving Management of Pediatric Pulmonary Arterial Hypertension: Impact of Phosphodiesterase Inhibitors
verfasst von
Andrew James Wardle
Robert M. R. Tulloh
Publikationsdatum
01.02.2013
Verlag
Springer-Verlag
Erschienen in
Pediatric Cardiology / Ausgabe 2/2013
Print ISSN: 0172-0643
Elektronische ISSN: 1432-1971
DOI
https://doi.org/10.1007/s00246-012-0598-8

Weitere Artikel der Ausgabe 2/2013

Pediatric Cardiology 2/2013 Zur Ausgabe

„Jeder Fall von plötzlichem Tod muss obduziert werden!“

17.05.2024 Plötzlicher Herztod Nachrichten

Ein signifikanter Anteil der Fälle von plötzlichem Herztod ist genetisch bedingt. Um ihre Verwandten vor diesem Schicksal zu bewahren, sollten jüngere Personen, die plötzlich unerwartet versterben, ausnahmslos einer Autopsie unterzogen werden.

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Schlechtere Vorhofflimmern-Prognose bei kleinem linken Ventrikel

17.05.2024 Vorhofflimmern Nachrichten

Nicht nur ein vergrößerter, sondern auch ein kleiner linker Ventrikel ist bei Vorhofflimmern mit einer erhöhten Komplikationsrate assoziiert. Der Zusammenhang besteht nach Daten aus China unabhängig von anderen Risikofaktoren.

Semaglutid bei Herzinsuffizienz: Wie erklärt sich die Wirksamkeit?

17.05.2024 Herzinsuffizienz Nachrichten

Bei adipösen Patienten mit Herzinsuffizienz des HFpEF-Phänotyps ist Semaglutid von symptomatischem Nutzen. Resultiert dieser Benefit allein aus der Gewichtsreduktion oder auch aus spezifischen Effekten auf die Herzinsuffizienz-Pathogenese? Eine neue Analyse gibt Aufschluss.

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.