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Medikamentöse Therapie der pulmonalen Hypertonie

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Medical treatment of pulmonary hypertension

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  • Arzneimitteltherapie
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Zusammenfassung

Die pulmonale Hypertonie (PH) ist eine chronisch progrediente Erkrankung der pulmonalen Zirkulation multifaktorieller Ursache. Die aktuelle diagnostische Klassifikation der PH unterscheidet fünf Hauptgruppen, die als Gemeinsamkeit einen erhöhten mittleren pulmonalarteriellen Druck und pulmonalen Gefäßwiderstand aufweisen. Klassifiziert werden die pulmonalarterielle Hypertonie (PAH), die PH durch Linksherzerkrankung, die PH bei Lungenerkrankungen und/oder Hypoxie, die chronische thromboembolische pulmonale Hypertonie (CTEPH) und die PH mit unklaren bzw. multifaktoriellen Mechanismen. Aktuelle Fortschritte in der Grundlagenforschung sowie die Zulassung neuer Medikamente und Etablierung von Therapiestrategien vor allem bei der PAH und CTEPH erfordern eine differenzierte Betrachtung der Erkrankung, eine sorgfältige Diagnosestellung und Therapieeinleitung sowie regelmäßige Verlaufskontrollen. In diesem Beitrag möchten wir einen aktuellen Überblick über die komplexe medikamentöse Therapie der PAH geben.

Abstract

Pulmonary hypertension (PH) is a chronic progressive disease of the pulmonary circulation of multifactorial causes. The current diagnostic classification of PH distinguishes five main groups, which have as a common feature an increased pulmonary arterial pressure and pulmonary resistance. The classification differentiates pulmonary arterial hypertension (PAH), PH due to left heart disease, PH in lung diseases and/or hypoxia, chronic thromboembolic pulmonary hypertension (CTEPH), and PH with unclear/multifactorial mechanisms. Recent advances in basic research with the approval of new drugs and the establishment of therapeutic strategies, mainly in PAH and CTEPH, require a differentiated view of the disease, a careful diagnosis and initiation of therapy, and regular follow-ups. In this article, we provide an overview of the complex drug therapy currently available for PAH patients.

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Literatur

  1. Badesch DB, Tapson VF, Mcgoon MD et al (2000) Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial. Ann Intern Med 132:425–434

    Article  CAS  PubMed  Google Scholar 

  2. Barst RJ, McGoon M, McLaughlin V et al (2003) Beraprost therapy for pulmonary arterial hypertension. J Am Coll Cardiol 41:2119–2125

  3. Barst RJ, Rubin LJ, Long WA et al (1996) A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med 334:296–301

  4. Channick RN, Simonneau G, Sitbon O et al (2001) Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet 358:1119–1123

    Article  CAS  PubMed  Google Scholar 

  5. Ewert R, Halank M, Bruch L et al (2012) A case series of patients with severe pulmonary hypertension receiving an implantable pump for intravenous prostanoid therapy. Am J Respir Crit Care Med 186:1196–1198

    Article  PubMed  Google Scholar 

  6. Fisher MR, Forfia PR, Chamera E et al (2009) Accuracy of Doppler echocardiography in the hemodynamic assessment of pulmonary hypertension. Am J Respir Crit Care Med 179:615–621

    Article  PubMed Central  PubMed  Google Scholar 

  7. Galie N, Brundage BH, Ghofrani HA et al (2009) Tadalafil therapy for pulmonary arterial hypertension. Circulation 119:2894–2903

    Article  CAS  PubMed  Google Scholar 

  8. Galie N, Corris PA, Frost A et al (2013) Updated treatment algorithm of pulmonary arterial hypertension. J Am Coll Cardiol 62:D60–D72

  9. Galie N, Ghofrani HA, Torbicki A et al (2005) Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med 353:2148–2157

  10. Galie N, Muller K, Scalise AV et al (2015) PATENT PLUS: a blinded, randomised and extension study of riociguat plus sildenafil in PAH. Eur Respir J (im Druck)

  11. Galie N, Olschewski H, Oudiz RJ et al (2008) Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2. Circulation 117:3010–3019

    Article  CAS  PubMed  Google Scholar 

  12. Galiè N, Rubin LJ, Hoeper MM et al (2008) Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind, randomised controlled trial. Lancet 371:2093–2100

    Article  PubMed  Google Scholar 

  13. Gatfield J, Mueller Grandjean C, Sasse T et al (2012) Slow receptor dissociation kinetics differentiate macitentan from other endothelin receptor antagonists in pulmonary arterial smooth muscle cells. PLoS One 7:e47662

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Ghofrani HA, D’Armini AM, Grimminger F et al (2013) Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med 369:319–329

  15. Ghofrani HA, Galie N, Grimminger F et al (2013) Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med 369:330–340

  16. Ghofrani HA, Humbert M (2014) The role of combination therapy in managing pulmonary arterial hypertension. Eur Respir Rev 23:469–475

    Article  PubMed  Google Scholar 

  17. Ghofrani HA, Seeger W, Grimminger F (2005) Imatinib for the treatment of pulmonary arterial hypertension. N Engl J Med 353:1412–1413

  18. Hoeper MM, Markevych I, Spiegerkoetter E et al (2005) Goal-oriented treatment and combination therapy for pulmonary arterial hypertension. Eur Respir J 26(5):858–863

    Article  Google Scholar 

  19. Hoeper MM, Barst RJ, Bourge RC et al (2013) Imatinib mesylate as add-on therapy for pulmonary arterial hypertension: results of the randomized IMPRES study. Circulation 127:1128–1138

    Article  CAS  PubMed  Google Scholar 

  20. Hoeper MM, Schwarze M, Ehlerding S et al (2000) Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue. N Engl J Med 342:1866–1870

  21. Humbert M, Barst RJ, Robbins IM et al (2004) Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2. Eur Respir J 24:353–359

    Article  Google Scholar 

  22. Jais X, D’Armini AM, Jansa P et al (2008) Bosentan for treatment of inoperable chronic thromboembolic pulmonary hypertension: BENEFiT (Bosentan Effects in iNopErable Forms of chronIc Thromboembolic pulmonary hypertension), a randomized, placebo-controlled trial. J Am Coll Cardiol 52:2127–2134

  23. Kemp K, Savale L, O’Callaghan DS et al (2012) Usefulness of first-line combination therapy with epoprostenol and bosentan in pulmonary arterial hypertension: an observational study. J Heart Lung Transplant 31:150–158

  24. Kylhammar D, Persson L, Hesselstrand R et al (2014) Prognosis and response to first-line single and combination therapy in pulmonary arterial hypertension. Scand Cardiovasc J 48:223–233

    Article  Google Scholar 

  25. McLaughlin V, Channick R, Ghofrani A (2014) Effect of bosentan and sildenafil combination therapy on morbidity and mortality in pulmonary arterial hypertension (PAH): results from the COMPASS-2 study. Chest 146:860A

    Article  Google Scholar 

  26. Nickel N, Golpon H, Greer M et al (2012) The prognostic impact of follow-up assessments in patients with idiopathic pulmonary arterial hypertension. Eur Respir J 39:589–596

    Article  Google Scholar 

  27. Olschewski H, Ghofrani HA, Walmrath D et al (1998) Recovery from circulatory shock in severe primary pulmonary hypertension (PPH) with aerosolization of iloprost. Intensive Care Med 24:631–634

    Article  CAS  PubMed  Google Scholar 

  28. Olschewski H, Simonneau G, Galie N et al (2002) Inhaled iloprost for severe pulmonary hypertension. N Engl J Med 347:322–329

  29. Oudiz RJ, Brundage BH, Galie N et al (2012) Tadalafil for the treatment of pulmonary arterial hypertension: a double-blind 52-week uncontrolled extension study. J Am Coll Cardiol 60:768–774

  30. Pulido T, Adzerikho I, Channick RN et al (2013) Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med 369:809–818

  31. Pullamsetti SS, Schermuly R, Ghofrani A et al (2014) Novel and emerging therapies for pulmonary hypertension. Am J Respir Crit Care Med 189:394–400

    Article  CAS  PubMed  Google Scholar 

  32. Rubin LJ, Badesch DB, Barst RJ et al (2002) Bosentan therapy for pulmonary arterial hypertension. N Engl J Med 346:896–903

  33. Rubin LJ, Badesch DB, Fleming TR et al (2011) Long-term treatment with sildenafil citrate in pulmonary arterial hypertension: the SUPER-2 study. Chest 140:1274–1283

    Article  CAS  PubMed  Google Scholar 

  34. Rubin LJ, Mendoza J, Hood M et al (1990) Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol). Results of a randomized trial. Ann Intern Med 112:485–491

    Article  CAS  PubMed  Google Scholar 

  35. Schermuly RT, Dony E, Ghofrani HA et al (2005) Reversal of experimental pulmonary hypertension by PDGF inhibition. J Clin Invest 115:2811–2821

  36. Simonneau G, Barst RJ, Galie N et al (2002) Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med 165:800–804

    Article  PubMed  Google Scholar 

  37. Simonneau G, Gatzoulis MA, Adatia I et al (2013) Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 62:D34–D41

  38. 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 149:521–530

    Article  PubMed  Google Scholar 

  39. Sitbon O, Galie N (2010) Treat-to-target strategies in pulmonary arterial hypertension: the importance of using multiple goals. Eur Respir Rev 19:272–278

    Article  CAS  PubMed  Google Scholar 

  40. Sitbon O, Jais X, Savale L et al (2014) Upfront triple combination therapy in pulmonary arterial hypertension: a pilot study. Eur Respir J 43:1691–1697

    Article  Google Scholar 

  41. Strange G, Gabbay E, Kermeen F et al (2013) Time from symptoms to definitive diagnosis of idiopathic pulmonary arterial hypertension: the delay study. Pulm Circ 3:89–94

    Article  PubMed Central  PubMed  Google Scholar 

  42. Strange G, Playford D, Stewart S et al (2012) Pulmonary hypertension: prevalence and mortality in the Armadale echocardiography cohort. Heart 98:1805–1811

    Article  PubMed Central  PubMed  Google Scholar 

  43. Tapson VF, Jing ZC, Xu KF et al (2013) Oral treprostinil for the treatment of pulmonary arterial hypertension in patients receiving background endothelin receptor antagonist and phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C2 study): a randomized controlled trial. Chest 144:952–958

    Article  CAS  PubMed  Google Scholar 

  44. Tapson VF, Torres F, Kermeen F et al (2012) Oral treprostinil for the treatment of pulmonary arterial hypertension in patients on background endothelin receptor antagonist and/or phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C study): a randomized controlled trial. Chest 142:1383–1390

    Article  CAS  PubMed  Google Scholar 

  45. Task Force For Diagnosis and Treatment of Pulmonary Hypertension of European Society of Cardiology (ESC), European Respiratory Society (ERS), International Society of Heart and Lung Transplantation (ISHLT) et al (2009) Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J 34:1219–1263

    Google Scholar 

  46. https://clinicaltrials.gov/ct2/show/NCT01247116

  47. https://clinicaltrials.gov/ct2/show/NCT01178073

  48. https://clinicaltrials.gov/ct2/show/NCT01106014

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Einhaltung ethischer Richtlinien

Interessenkonflikt. M.J. Richter erhielt Vortragshonorare von United Therapeutics/OMT sowie Fortbildungsunterstützung von Bayer. H. Gall erhält finanzielle Unterstützung für seine Forschung und/oder Honorare von Actelion, AstraZeneca, Bayer, GlaxoSmithKline, Janssen-Cilag, Lilly, Pfizer und United Therapeutics/OMT. K. Tello erhielt Vortragshonorare und Fortbildungsunterstützung von Actelion sowie Fortbildungsunterstützung von Bayer. N. Sommer erhielt Vortragshonorare von Actelion und Bayer. F. Grimminger und W. Seeger erhielten Vortragshonorare von Pfizer und Bayer und sind als Berater für Bayer tätig. H.A. Ghofrani erhielt Vortragshonorare von Actelion, Bayer, Ergonex, Gilead, GSK, Novartis und Pfizer, erhält Forschungsförderungen von Actelion, Bayer, Ergonex und Pfizer, ist Gremienmitglied bei Actelion, Bayer, Ergonex, GSK, Novartis, Pfizer und ist als Berater für Actelion, Bayer, Ergonex, Gilead, GSK, Merck, Novartis und Pfizer tätig.

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Richter, M., Gall, H., Tello, K. et al. Medikamentöse Therapie der pulmonalen Hypertonie. Internist 56, 573–582 (2015). https://doi.org/10.1007/s00108-015-3693-0

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