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Der Klinikarzt 2017; 46(08): 374-381
DOI: 10.1055/s-0043-116604
Schwerpunkt
© Georg Thieme Verlag Stuttgart · New York

Therapie der pulmonal arteriellen Hypertonie

Behandlungsstrategien und Stellenwert von Kombinationstherapien
Stephan Rosenkranz
1   Klinik III für Innere Medizin, Herzzentrum der Universität zu Köln
2   Cologne Cardiovascular Research Center (CCRC), Herzzentrum der Universität zu Köln
,
H. Ardeschir Ghofrani
3   Universities of Giessen and Marburg Lung Center (UGMLC), Gießen
4   Department of Medicine, Imperial College, London, UK
5   Deutsches Zentrum für Lungenforschung (DZL)
,
Marius M. Hoeper
5   Deutsches Zentrum für Lungenforschung (DZL)
6   Klinik für Pneumologie, Medizinische Hochschule, Hannover
› Author Affiliations
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Publication History

Publication Date:
24 August 2017 (online)

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Zusammenfassung

Die Betreuung von Patienten mit pulmonal arterieller Hypertonie (PAH) basiert auf einer komplexen Strategie, welche neben dem Einsatz gezielter PAH-Medikamente auch Allgemeinmaßnahmen und supportive Therapien einschließt. Gezielte PAH-Therapien umfassen Endothelin-Rezeptor-Antagonisten, Phosphodiesterase 5-Inhibitoren, Stimulatoren der löslichen Guanylatzyklase, Prostazyklin-Analoga und Prostazyklin-Rezeptor-Agonisten, die als Mono- oder Kombinationstherapien eingesetzt werden. Vor Einleitung einer gezielten PAH-Therapie sollten die Patienten zur Diagnosesicherung und Klassifikation in einem Expertenzentrum vorgestellt werden. Therapieentscheidungen basieren auf der initialen Ermittlung der Krankheitsschwere und einer individuellen Risikostratifizierung, dem Vorhandensein von Komorbiditäten und Risikofaktoren, dem Therapieansprechen und dem Krankheitsverlauf. Die aktuellen ESC/ERS-Leitlinien und die Empfehlungen der Kölner Konsensus-Konferenz betonen den Stellenwert von Kombinationstherapien, wobei je nach Vorhandensein kardialer und/oder pulmonaler Begleiterkrankungen zwischen „typischer" und „atypischer" PAH unterschieden werden sollte. Allgemeinmaßnahmen und supportive Therapien haben zum Teil erheblichen Einfluss auf die Morbidität und Mortalität und sind daher integraler Bestandteil der Behandlung und Versorgung von PAH-Patienten.

 

  • Literatur

  • 1 Galiè N, Humbert M, Vachiery JL. et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J 2015; 46: 903-975
    CrossrefPubMedGoogle Scholar
  • 2 Galiè N, Humbert M, Vachiery JL. et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J 2016; 37: 67-119
    CrossrefPubMedGoogle Scholar
  • 3 Galiè N, Barbera JA, Frost AE. et al. Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension. N Engl J Med 2015; 373: 834-844
    CrossrefPubMedGoogle Scholar
  • 4 Pulido T, Adzerikho I, Channick RN. et al. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med 2013; 369: 809-818
    CrossrefPubMedGoogle Scholar
  • 5 Sitbon O, Channick R, Chin KM. et al. Selexipag for the Treatment of Pulmonary Arterial Hypertension. 2015; 373: 2522-2533
    PubMedGoogle Scholar
  • 6 Jing ZC, Jiang X, Han ZY. et al. Iloprost for pulmonary vasodilator testing in idiopathic pulmonary arterial hypertension. Eur Respir J 2009; 33: 1354-1360
    CrossrefPubMedGoogle Scholar
  • 7 Rosenkranz S. Pulmonary hypertension 2015: Current definitions, terminology, and novel treatment options. Clin Res Cardiol 2015; 104: 197-207
    CrossrefPubMedGoogle Scholar
  • 8 Hoeper MM, Apitz C, Grünig E. et al. Gezielte Therapie der pulmonal arteriellen Hypertonie: Empfehlungen der Kölner Konsensus-Konferenz 2016. Dtsch Med Wochenschr 2016; 141: S33-S41
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Kylhammar D, Kjellström B, Hjalmarsson C. et al. A comprehensive risk stratification at early follow-up determines prognosis in pulmonary arterial hypertension. Eur Heart J. 2017 [Epub ahead of print]
    PubMedGoogle Scholar
  • 10 Hoeper MM, Kramer T, Pan Z. et al. Mortality in pulmonary arterial hypertension: Prediction by the 2015 European Pulmonary Hypertension Guidelines risk stratification model. Eur Respir J. 2017 [Epub ahead of print]
    PubMedGoogle Scholar
  • 11 Boucly A, Weatherald J, Savale L. et al. Risk assessment, prognosis and guideline implementation in pulmonary arterial hypertension. Eur Respir J. 2017 [Epub ahead of print]
    PubMedGoogle Scholar
  • 12 Leuchte HH, ten Freyhaus H, Gall H. et al. Risikostratifizierung und Verlaufskontrollen bei PAH-Patienten: Empfehlungen der Kölner Konsensus-Konferenz 2016. Dtsch Med Wochenschr 2016; 141: S19-S25
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Galiè N, Corris PA, Frost A. et al. Updated treatment algorithm of pulmonary arterial hypertension. J Am Coll Cardiol 2013; 62 (Suppl D) D60-D72
    CrossrefPubMedGoogle Scholar
  • 14 Lajoie AC, Lauziere G, Lega JC. et al. Combination therapy versus monotherapy for pulmonary arterial hypertension: a meta-analysis. Lancet Respir Med 2016; 4: 291-305
    CrossrefPubMedGoogle Scholar
  • 15 Hoeper MM, McLaughlin VV, Galiè N. et al. Initial combination therapy with ambrisentan and tadalafil and mortality in patients with pulmonary arterial hypertension. A secondary analysis of the results from the randomized, controlled AMBITION study. Lancet Respir Med 2016; 4: 894-901
    CrossrefPubMedGoogle Scholar
  • 16 Hoeper MM, Huscher D, Pittrow D. Incidence and prevalence of pulmonary arterial hypertension in Germany. Int J Cardiol 2016; 203: 612-613
    CrossrefPubMedGoogle Scholar
  • 17 Mueller-Mottet S, Stricker H, Domenighetti G. et al. Long-term data from the Swiss pulmonary hypertension registry. Respiration 2015; 89: 127-140
    CrossrefPubMedGoogle Scholar
  • 18 Radegran G, Kjellstrom B, Ekmehag B. et al. Characteristics and survival of adult Swedish PAH and CTEPH patients 2000–2014. 2016; 50: 243-250
    PubMedGoogle Scholar
  • 19 Hoeper MM, Humbert M, Souza R. et al. A global view of pulmonary hypertension. Lancet Respir Med 2016; 4: 306-322
    CrossrefPubMedGoogle Scholar
  • 20 Opitz CF, Hoeper MM, Gibbs JSR. et al. Pre-capillary, combined, and post-capillary pulmonary hypertension: A pathophysiological continuum. J Am Coll Cardiol 2016; 68: 368-378
    CrossrefPubMedGoogle Scholar
  • 21 Hoeper MM, Meyer K, Rademacher J. et al. Diffusion capacity and mortality in patients with pulmonary hypertension due to heart failure with preserved ejection fraction. J Am Coll Cardiol HF 2016; 4: 441-449
    PubMedGoogle Scholar
  • 22 Trip P, Nossent EJ, de Man FS. et al. Severely reduced diffusion capacity in idiopathic pulmonary arterial hypertension: patient characteristics and treatment responses. Eur Respir J 2013; 42: 1575-1585
    CrossrefPubMedGoogle Scholar
  • 23 Grünig E, Benjamin N, Krüger U. et al. Allgemeine und supportive Therapie der pulmonal arteriellen Hypertonie: Empfehlungen der Kölner Konsensus-Konferenz 2016. Dtsch Med Wochenschr 2016; 141: S26-S32
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Jais X, Olsson KM, Barbera JA. et al. Pregnancy outcomes in pulmonary arterial hypertension in the modern management era. Eur Respir J 2012; 40: 881-885
    CrossrefPubMedGoogle Scholar
  • 25 Duarte AG, Thomas S, Safdar Z. et al. Management of pulmonary arterial hypertension during pregnancy: a retrospective, multicenter experience. Chest 2013; 143: 1330-1336
    CrossrefPubMedGoogle Scholar
  • 26 Burns RM, Peacock AJ, Johnson MK. et al. Hypoxaemia in patients with pulmonary arterial hypertension during simulated air travel. Respir Med 2013; 107: 298-304
    CrossrefPubMedGoogle Scholar
  • 27 Olsson KM, Delcroix M, Ghofrani HA. et al. Anticoagulation and survival in pulmonary arterial hypertension: results from the Comparative, Prospective Registry of Therapies for Pulmonary Hypertension (COMPERA). Circulation 2014; 129: 57-65
    CrossrefPubMedGoogle Scholar
  • 28 Galiè N, Delcroix M, Ghofrani A. et al. Anticoagulant therapy does not influence long-term outcomes in patients with pulmonary arterial hypertension (PAH): insights from the randomised controlled SERAPHIN trial of macitentan. Eur Heart J 2014; 35: 10
    CrossrefPubMedGoogle Scholar
  • 29 Preston RJ, Roberts KE, Miller DP. et al. Effect of warfarin treatment on survival of patients with pulmonary arterial hypertension (PAH) in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL). Am J Respir Crit Care Med 2014; 189: A2464
    PubMedGoogle Scholar
  • 30 Maron BA, Waxman AB, Opotowsky AR. et al. Effectiveness of spironolactone plus ambrisentan for treatment of pulmonary arterial hypertension (from the [ARIES] study 1 and 2 trials). Am J Cardiol 2013; 112: 720-725
    CrossrefPubMedGoogle Scholar
  • 31 Weitzenblum E, Sautegeau A, Ehrhart M. et al. A. Long-term oxygen therapy can reverse the progression of pulmonary hypertension in patients with chronic obstructive pulmonary disease. Am Rev Respir Dis 1985; 131: 493-498
    CrossrefPubMedGoogle Scholar
  • 32 Ulrich S, Hasler ED, Saxer S. et al. Effect of breathing oxygen-enriched air on exercise performance in patients with precapillary pulmonary hypertension: randomized, sham-controlled cross-over trial. Eur Heart J 2017; 38: 1159-1168
    CrossrefPubMedGoogle Scholar
  • 33 Rhodes CJ, Howard LS, Busbridge M. et al. Iron deficiency and raised hepcidin in idiopathic pulmonary arterial hypertension clinical prevalence, outcomes, and mechanistic insights. J Am Coll Cardiol 2011; 8: 300-309
    PubMedGoogle Scholar
  • 34 Melenovsky V, Petrak J, Mracek T. et al. Myocardial iron content and mitochondrial function in human heart failure: a direct tissue analysis. Eur J Heart Fail 2017; 19: 522-530
    CrossrefPubMedGoogle Scholar
  • 35 Viethen T, Gerhardt F, Dumitrescu D. et al. Ferric carboxymaltose improves exercise capacity and quality of life in patients with pulmonary arterial hypertension and iron deficiency: a pilot study. Int J Cardiol 2014; 175: 233-239
    CrossrefPubMedGoogle Scholar
  • 36 Hoeper MM, Galie N, Murali S. et al. Outcome after cardiopulmonary resuscitation in patients with pulmonary arterial hypertension. Am J Respir Crit Care Med 2002; 165: 341-344
    CrossrefPubMedGoogle Scholar
  • 37 Olsson KM, Nickel NP, Tongers J. et al. Atrial flutter and fibrillation in patients with pulmonary hypertension. Int J Cardiol 2013; 167: 2300-2305
    CrossrefPubMedGoogle Scholar
  • 38 Showkathali R, Tayebjee MH, Grapsa J. et al. Right atrial flutter isthmus ablation is feasible and results in acute clinical improvement in patients with persistent atrial flutter and severe pulmonary arterial hypertension. Int J Cardiol 2011; 149: 279-280
    CrossrefPubMedGoogle Scholar
  • 39 Tudorache I, Sommer W, Kuhn C. et al. Lung transplantation for severe pulmonary hypertension-awake extracorporeal membrane oxygenation for postoperative left ventricular remodelling. Transplantation 2015; 99: 451-458
    CrossrefPubMedGoogle Scholar