Combination therapy is a new standard for treatment of pulmonary arterial hypertension


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Abstract

At present, compelling evidence has been obtained that combined therapy of pulmonary arterial hypertension (PAH) with specific drugs can significantly slow progression of PAH. Therefore, in current guidelines combination therapy is already considered as standard treatment for a significant proportion of patients with moderately severe and severe forms of PAH. However, the quality of life and long-term prognosis of patients receiving combination therapy, should be the object of further research. The future research is absolutely necessary to identify the most optimal strategy of treatment of patients with PAH, such as initial combination therapy or rapid sequential combination therapy, double or triple combinations as well as exploring new signaling pathways PAH, which can become targets for new specific drugs PAH.

About the authors

S N Avdeev

I.M. Sechenov First Moscow State Medical University

Email: serg_avdeev@list.ru
д.м.н., проф., член-корр. РАН, зав. каф. пульмонологии ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» Минздрава России; руководитель клинического отдела ФГБУ «НИИ пульмонологии» ФМБА России Moscow, Russia

N A Tsareva

I.M. Sechenov First Moscow State Medical University

Email: n_tsareva@mail.ru
к.м.н., доцент каф. пульмонологии ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» Минздрава России; зав. лаб. интенсивной пульмонологии и дыхательной недостаточности ФГБУ «НИИ пульмонологии» ФМБА России Moscow, Russia

I R Gaisin

Izhevsk State Medical Academy

Email: igaisin@mail.ru
д.м.н., проф. каф. госпитальной терапии с курсами кардиологии и функциональной диагностики ФПК и ПП ФГБОУ ВО «Ижевская государственная медицинская академия» Минздрава России Izhevsk, Russia

References

  1. Galiè N, Humbert M, Vachiery J.L 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. doi: 10.1093/eurheartj/ehv317. Epub 2015 Aug 29.
  2. Чазова И.Е., Авдеев С.Н., Царева Н.А., Волков А.В., Мартынюк Т.В., Наконечников С.Н. Клинические рекомендации по диагностике и лечению легочной гипертонии. Терапевтический архив. 2014; (9): 4-23.
  3. Humbert M, Souza R, Galie N, Mc Laughlin V, Simonneau G, Rubin L. Pulmonary arterial hypertension: bridging the present to the future. Eur Respir Rev. 2012; 21: 126, 267-270.
  4. Simonneau G, Gatzolis G, Adatia I et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2013; 62(25 Suppl): D35-41.
  5. Hoeper M.M, Huscher D, Ghofrani H.A et al. Elderly patients diagnosed with idiopathic pulmonary arterial hypertension: results from the COMPERA registry. Int J Cardiol. 2013; 168: 871-880.
  6. Humbert M, Sitbon O, Yaici A et al. Survival in incident and prevalent cohort of patients with pulmonary arterial hypertension. Eur Respir J. 2010; 36: 549-555.
  7. Frost A.E, Badesch D.B, Miller D.P et al. Evaluation of the predictive value of a clinical worsening definition using 2-year outcomes in patients with pulmonary arterial hypertension: a REVEAL Registry analysis. Chest. 2013; 144: 1521-1529.
  8. Nickel N, Golpon H, Greer M et al. The prognostic impact of follow - up assessments in patients with idiopathic pulmonary arterial hypertension. Eur Respir J. 2012; 39: 589-596.
  9. Boucly A, Weatherald J, Savale L et al. Risk assessment, prognosis and guideline implementation in pulmonary arterial hypertension. Eur Respir J. 2017; 50: 1700889 [https://doi.org/10.1183/13993003.00889-2017].
  10. Hoeper M.M, 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; 50: 1700740. https://doi.org/10.1183/13993003.00740-2017.
  11. Benza R.L, Miller D.P, Gomberg-Maitland M et al. Predicting survival in pulmonary arterial hypertension: insights from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL). Circulation. 2010; 122: 164-172.
  12. Barst R.J, Rubin L.J, Long W.A et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. The Primary Pulmonary Hypertension Study Group. N Engl J Med. 1996; 334: 296-302.
  13. Mc Laughlin V.V, Shillington A, Rich S. Survival in primary pulmonary hypertension: the impact of epoprostenol therapy. Circulation. 2002; 106: 1477-1482.
  14. Channick R.N, Simonneau G, Sitbon O et al. Effects of the dual endothelin - receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo - controlled study. Lancet. 2001; 358: 1119-1123.
  15. Barst R.J, Langleben D, Badesch D et al. Treatment of pulmonary arterial hypertension with the selective endothelin-A receptor antagonist sitaxsentan. J Am Coll Cardiol. 2006; 47: 2049-2056.
  16. Galiè N, Rubin L.J, Hoeper M.M et al. Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double - blind, randomised controlled trial. Lancet. 2008; 371: 2093-2100.
  17. Galiè N, Brundage B.H, Ghofrani H.A et al. Tadalafil therapy for pulmonary arterial hypertension. Circulation. 2009; 119: 2894-2903.
  18. Авдеев С.Н., Царева Н.А., Неклюдова Г.В., Чучалин А.Г. Первый клинический опыт применения антагониста рецепторов эндотелина бозентана у пациентов с легочной артериальной гипертензией: результаты 1-годичного исследования. Терапевтический архив. 2013; (3): 38-43.
  19. Авдеев С.Н. Новый антагонист рецепторов эндотелина мацитентан: перспективы терапии легочной артериальной гипертонии. Терапевтический архив. 2016; (7): 89-97.
  20. Frishman W.H, Landau A, Cretkovic A. Combination drug therapy with calcium - channel blockers in the treatment of systemic hypertension. J Clin Pharmacol. 1993; 33: 752-755.
  21. Pitt B, Zannad F, Remme W.J et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999; 341: 709-717.
  22. Wedzicha J.A, Banerji D, Chapman K.R, Vestbo J, Roche N, Ayers R.T, Thach C, Fogel R, Patalano F, Vogelmeier C. Indacaterol - glycopyrronium versus salmeterol - fluticasone for COPD. N Engl J Med. 2016; 374: 2222-34.
  23. Lajoie A-C, Bonnet S, Provencher S. Combination therapy in pulmonary arterial hypertension: recent accomplishments and future challenges. Pulmonary Circulation. 2017; 7: 312-325.
  24. Sitbon O, Gaine S. Beyond a single pathway: combination therapy in pulmonary arterial hypertension. Eur Respir Rev. 2016; 25:408-417. doi: 10.1183/16000617.0085-2016.
  25. Humbert M, Barst R.J, Robbins I.M et al. Combination of bosentan with epoprostenol in pulmonary arterial hypertension: BREATHE-2. Eur Respir J. 2004; 24: 353-359.
  26. Hoeper M.M, Leuchte H, Halank M et al. Combining inhaled iloprost with bosentan in patients with idiopathic pulmonary arterial hypertension. Eur Respir J. 2006; 28: 691-694.
  27. Simonneau G, Rubin L.J, Galiè N et al. Addition of sildenafil to long - term intravenous epoprostenol therapy in patients with pulmonary arterial hypertension: a randomized trial. Ann Intern Med. 2008; 149: 521-530.
  28. Galiè N, Barbera J.A, Frost A et al. Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension. N Engl J Med. 2015; 379: 834-844. doi: 10.1056/NEJMoa1413687.
  29. Galiè N, Palazzini M, Manes A. Pulmonary arterial hypertension: from the kingdom of the near - dead to multiple clinical trial meta - analyses. Eur Heart J. 2010; 31: 2080-2086. doi: 10.1093/eurheartj/ehq152.
  30. Царева Н.А., Авдеев С.Н., Неклюдова Г.В. Последовательная комбинированная терапия больной с идиопатической легочной артериальной гипертензией. Кардиология. 2016; (3): 97-100. doi: https://dx.doi.org/10. 18565/cardio.2016.3.97-100
  31. Царева Н.А., Авдеев С.Н., Неклюдова Г.В. Пациент с тяжелым течением идиопатической легочной артериальной гипертензии: есть ли выход? Терапевтический архив. 2017; (9): 100-103. doi: 10.17116/terarkh 2017899100-103
  32. Lajole A.C, Lauzière G., Lega J.C et al. Combination therapy versus monotherapy for pulmonary arterial hypertension: a meta - analysis. Lancet Resp Med. 2016; 4:291-305. doi: 10.1016/S2213-2600(16) 00027-8.
  33. Fox B.D, Shtraichman O, Langleben D et al. Combination therapy for pulmonary arterial hypertension a systematic review and meta - analysis. Can J Cardiol. 2016; 32: 1520-1530.
  34. Mc Laughlin V.V, Oudiz R.J, Frost A et al. Randomized study of adding inhaled iloprost to existing bosentan in pulmonary arterial hypertension. Am J Respir Crit Care Med. 2006; 174: 1257-1263.
  35. Tapson V.F, Torres F, Kermeen F et al. Oral treprostinil for the treatment of pulmonary arterial hypertension in patients on background endothelin receptor antagonist and/or phosphodiesterase type 5 inhibitor therapy (the FREEDOMC study): A randomized controlled trial. Chest. 2012; 142: 1383-1390.
  36. Tapson V.F, Jing Z-C, Xu K-F et al. 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. 2013; 144: 952-958.
  37. Mc Laughlin V, Benza R.L, Rubin L.J et al. Addition of inhaled treprostinil to oral therapy for pulmonary arterial hypertension: a randomized controlled clinical trial. J Am Coll Cardiol. 2010; 55: 1915-1922.
  38. Sitbon O, Channick R, Chin K.M et al. Selexipag for the Treatment of Pulmonary Arterial Hypertension. N Engl J Med. 2015; 373:2522-2533. doi: 10.1056/NEJMoa1503184.
  39. Pulido T, Adzerikho I, Channick R.N et al. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med. 2013; 369:809-18.
  40. Mc Laughlin V, Channick R.N, Ghofrani H-A et al. Bosentan added to sildenafil therapy in patients with pulmonary arterial hypertension. Eur Respir J. 2015; 46: 1-9.
  41. Gruenig E, Michelakis E, Vachiéry J.L, Vizza C.D, Meyer F.J, Doelberg M, Bach D, Dingemanse J, Galiè N. Acute hemodynamic effects of single - dose sildenafil when added to established bosentan therapy in patients with pulmonary arterial hypertension: results of the COMPASS-1 study. J Clin Pharmacol. 2009; 49: 1343-52. doi: 10.1177/ 0091270009341182.
  42. Barst R.J, Oudiz R.J, Beardsworth A et al. Tadalafil monotherapy and as add - on to background bosentan in patients with pulmonary arterial hypertension. J Heart Lung Transplant. 2011; 30: 632-643.
  43. Ghofrani H-A, Galie N, Grimminger F et al. Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med. 2013; 369: 330-340.
  44. Kemp K, Savale L, O’Callaghan D.S et al. Usefulness of first - line combination therapy with epoprostenol and bosentan in pulmonary arterial hypertension: an observational study. J Heart Lung Transplant. 2012; 31: 150-158. doi: 10.1016/j.healun.2011.11.002.
  45. Sitbon O, Jaїs X, Savale L et al. Upfront triple combination therapy in pulmonary arterial hypertension: a pilot study. Eur Respir J. 2014; 43: 1691-1697. doi: 10.1183/09031936.00116313.
  46. Hoeper M.M, Mc Laughlin V.V, Barbera J.A 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 randomised, controlled AMBITION study. Lancet Respir Med. 2016; 4: 894-901.
  47. Sitbon O, Sattler C, Bertoletti L et al. Initial dual oral combination therapy in pulmonary arterial hypertension. Eur Respir J. 2016; 47: 1727-1736.
  48. Jansa P, Pulido T. Macitentan in Pulmonary Arterial Hypertension: A Focus on Combination Therapy in the SERAPHIN Trial. Am J Cardiovasc Drugs. 2017 Dec 26. doi: 10.1007/s40256-017-0260-1. [Epub ahead of print].
  49. Coghlan J.G, Channick R, Chin K, Di Scala L, Galiè N, Ghofrani H.A, Hoeper M.M, Lang I.M, Mc Laughlin V, Preiss R, Rubin L.J, Simonneau G, Sitbon O, Tapson V.F, Gaine S. Targeting the Prostacyclin Pathway with Selexipag in Patients with Pulmonary Arterial Hypertension Receiving Double Combination Therapy: Insights from the Randomized Controlled GRIPHON Study. Am J Cardiovasc Drugs. 2018 Jan 6. doi: 10.1007/s40256-017-0262-z. [Epub ahead of print].
  50. Actelion. The Efficacy and Safety of Initial Triple Versus Initial Dual Oral Combination Therapy in Patients With Newly Diagnosed Pulmonary Arterial Hypertension (TRITON). Clinical Trials. gov. 2017: NCT02558231.

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