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Место антагонистов рецепторов эндотелина в лечении легочной гипертензии
Место антагонистов рецепторов эндотелина в лечении легочной гипертензии
Шостак Н.А., Клименко А.А., Андрияшкина Д.Ю., Демидова Н.А. Место антагонистов рецепторов эндотелина в лечении легочной гипертензии. Consilium Medicum. 2019; 21 (12): 74–80. DOI: 10.26442/20751753.2019.12.190424
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Аннотация
В статье представлены новые данные о применении антагонистов рецепторов эндотелина (АРЭ) в лечении больных различными вариантами легочной гипертензии. Описаны механизмы действия препаратов, приведены результаты клинических исследований по изучению их эффективности и безопасности, перспективы применения АРЭ в клинической практике. АРЭ являются одними из наиболее изученных классов препаратов, рекомендованных к применению у больных идиопатической легочной артериальной гипертензией (ЛАГ), ЛАГ вследствие системной склеродермии и при синдроме Эйзенменгера уже при начальных стадиях легочной гипертензии. Показано, что эта группа препаратов положительно влияет на функциональные, клинические, и гемодинамические параметры, увеличивает продолжительность и качество жизни этой тяжелой группы больных. Препараты эффективны как в монотерапии, так и при комбинированном лечении. По сравнению с другими ЛАГ-специфическими препаратами, наибольшую доказательную базу по количеству рандомизированных клинических исследований имеет бозентан, единственный в России препарат, который зарегистрирован в том числе для лечения детей. Согласно данным российского регистра больных ЛАГ среди АРЭ 31,6% больных получают бозентан, 3,6% – амбризентан, 2,1% – мацитентан. Бозентан занимает 2-е место по частоте назначения при ЛАГ после силденафила – 31,6 и 54,5% соответственно.
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The article presents new data on the use of endothelin receptor antagonists (ERA) in treatment of patients with different variants of pulmonary hypertension. The medications mechanisms of action are described and results of clinical studies on effectiveness and safety of the medications, perspectives on ERA use in clinical practice are presented. ERA is one of the best studied class of medications recommended for use in patients with idiopathic pulmonary arterial hypertension (PAH), PAH associated with generalized scleroderma and in Eisenmenger's syndrome in early stages of pulmonary hypertension. It was shown that this group of medications had a positive effect on functional, clinical and hemodynamic parameters, and increases life expectancy and quality of life in these serious cases. These medications are effective not only as monotherapy but also in combination treatment. Among medications for PAH treatment bosentan has the best evidence-based results according to the number of randomized clinical trials. It is the only medication from this group registered in Russia for children treatment. According to Russian register data among ERA in PAH patients 31.6% of patients use bosentan, 3.6% – ambrisentan, and 2.1% – macitentan. Bosentan is the second medication after sildenafil that is being used in PAH, in 31.6 and 54.5% of patients, respectively.
Key words: pulmonary hypertension, pathogenic mechanisms of pulmonary hypertension development, pulmonary arterial hypertension treatment, endothelin receptor antagonists, bosentan, macitentan.
Полный текст
Список литературы
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24. Bishop BM, Mauro VF, Khouri SJ. Practical considerations for the pharmacotherapy of pulmonary arterial hypertension. Pharmacotherapy 2012; 32: 838–55.
25. Chazova I.E., Arkhipova O.A., Martynyuk T.V. Pulmonary arterial hypertension in Russia: six-year observation analysis of the National Registry. Therapeutic Archive. 2019; 91 (1): 24–31. DOI: 10.26442/00403660.2019.01.000024
26. Chazova I.E., Arkhipova O.A., Valieva Z.S. et al. Legochnaia gipertenziia v Rossii: pervye rezul'taty natsional'nogo registra. Therapeutic Archive. 2014; 86 (9): 56–64 (in Russian).
27. Martyniuk T.V., Nakonechnikov S.N., Chazova I.E. Optimizatsiia spetsificheskoi terapii legochnoi arterial'noi gipertenzii: vozmozhnosti primeneniia antagonistov retseptorov endotelina. Evraziiskii kardiologicheskii zhurn. 2017; 2: 20–7 (in Russian).
28. Provencher S, Sitbon O, Humbert M et al. Long-term outcome with first-line bosentan therapy in idiopathic pulmonary arterial hypertension. Eur Heart J 2006; 27 (5): 589–95.
29. Chazova I.E., Avdeev S.N., Tsareva N.A. et al. Klinicheskie rekomendatsii po diagnostike i lecheniiu legochnoi gipertenzii. Therapeutic Archive. 2014; 9: 4–23 (in Russian).
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32. Naert A, De Haes P. Successful treatment with bosentan of lower extremity ulcers in a scleroderma patient. Case Rep Med 2013; 2013: 690591.
33. Hamaguchi Y, Sumida T, Kawaguchi Y. Safety and tolerability of bosentan for digital ulcers in Japanese patients with systemic sclerosis: Prospective, multicenter, open-label study. J Dermatol 2017; 44 (1): 13–7.
34. Matucci-Cerinic M, Denton CP, Furst DE et al. Bosentan treatment of digital ulcers related to systemic sclerosis: results from the RAPIDS-2 randomised, double-blind, placebo-controlled trial. Ann Rheum Dis 2011; 70 (1): 32–8.
35. Nagai Y, Hasegawa M, Hattori T et al. Bosentan for digital ulcers in patients with systemic sclerosis. J Dermatol 2012; 39 (1): 48–51.
36. Baughman RP, Culver DA, Cordova FC et al. Bosentan for sarcoidosis-associated pulmonary hypertension: a double-blind placebo controlled randomized trial. Chest 2014; 145 (4): 810–7.
37. Surie S, Reesink HJ, Marcus JT et al. Clin Bosentan treatment is associated with improvement of right ventricular function and remodeling in chronic thromboembolic pulmonary hypertension. Cardiol 2013; 36 (11): 698–703.
38. Hoeper MM, Madani MM, Nakanishi N et al. Chronic thromboembolic pulmonary hypertension. Lancet Respir Med 2014; 2 (7): 573–82.
39. Nishikawa-Takahashi M, Ueno S, Kario K. Long-term advanced therapy with bosentan improves symptoms and prevents deterioration of inoperable chronic thromboembolic pulmonary hypertension. Life Sci 2014; 118 (2): 410–3.
40. Jaïs X, D'Armini AM, Jansa P et al. Bosentan Effects in iNopErable Forms of chronIc Thromboembolic pulmonary hypertension), a randomized, placebo-controlled trial. J Am Coll Cardiol 2008;
52 (25): 2127–34. DOI: 10.1016/j.jacc.2008.08.059
41. Guo L, Liu YJ, Xie ZL. Safety and tolerability evaluation of oral bosentan in adult congenital heart disease associated pulmonary arterial hypertension: a systematic review and meta-analysis. Eur Rev Med Pharmacol Sci 2014; 18 (5): 638–45.
42. Shmal'ts A.A., Belkina M.V., Gorbachevskii S.V. Spetsificheskie legochnye vazodilatatory posle operatsii Fontena. Detskie bolezni serdtsa i sosudov. 2017; 14 (1): 16–24 (in Russian).
43. Maiya S, Hislop AA, Flynn Y, Haworth SG. Response to bosentan in children with pulmonary hypertension. Heart 2006; 92: 664–70.
44. Rosenzweig EB, Ivy DD, Widlitz A et al. Effects of long-term bosentan in children with pulmonary arterial hypertension. J Am Coll Cardiol 2005; 46: 697–704.
45. Mohamed WA, Ismail M. A randomized, double-blind, placebo-controlled, prospective study of bosentan for the treatment of persistent pulmonary hypertension of the newborn. J Perinatol 2012;
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46. Maneenil G, Thatrimontrichai A, Janjindamai W, Dissaneevate S. Effect of bosentan therapy in persistent pulmonary hypertension of the newborn. Pediatr Neonatol 2018; 59 (1): 58–64.
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47. Bolli MN, Boss C, Binkert C et al. The discovery of N-[5-94-bromophenyl0-6-[2-[95-bromo-2-pyrimidinyl) oxy]ethoxy]-4-pyrimidinyl]-N'-propylsulfamide (Macitentan), an orally active, potent dual endothelin receptor antagonist. J Med Chem 2012; 55: 7849–61. DOI: 10.1021/jm3009103
48. Gatfield J, Mueller Grandjean C, Sasse T et al. Slow receptor dissociation kinetics differentiate macitentan from other endothelin receptor antagonists in pulmonary arterial smooth muscle cells. PLoS One 2012; 7 (10): e47662. DOI: 10.1371/journal.pone.0047662
49. Sidharta PN, van Giersbergen PL, Dingemanse J. Safety, tolerability, pharmacokinetics, and pharmacodynamics of macitentan, an endothelin receptor antagonist, in an ascending multiple-dose study in healthy subjects. J Clin Pharmacol 2013; 53 (11): 1131–8. DOI: 10.1002/jcph.152
50. Pulido T, Adzerikho I, Channick RN, et al. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med. 2013; 369 (9): 809–18. DOI: 10.1056/NEJMoa1213917/
51. Channick RN, Delcroix M, Ghofrani HA et al. Effect of macitentan on hospitalizations: results from the SERAPHIN trial. JACC Heart Fail 2015; 3 (1): 1–8. DOI: 10.1016/j.jchf.2014.07.013
52. Simonneau G, Channick RN, Delcroix M et al. Incident and prevalent cohorts with pulmonary arterial hypertension: insight from SERAPHIN. Eur Respir J 2015; 46 (6): 1711–20. DOI: 10.1183/13993003.00364-2015
53. Aypar E, Alehan D, Karagöz T et al. Clinical efficacy and safety of switch from bosentan to macitentan in children and young adults with pulmonary arterial hypertension. Cardiol Young 2018;
28 (4): 542–7. DOI: 10.1017/S1047951117002542
54. Vachiéry JL, Delcroix M, Al-Hiti H et al. Macitentan in pulmonary hypertension due to left ventricular dysfunction. Eur Respir J 2018; 51 (2); pii: 1701886. DOI: 10.1183/13993003.01886-2017
55. Khanna D, Denton CP, Merkel PA et al. Effect of Macitentan on the Development of New Ischemic Digital Ulcers in Patients With Systemic Sclerosis: DUAL-1 and DUAL-2 Randomized Clinical Trials. JAMA 2016; 315 (18): 1975–88. DOI: 10.1001/jama.2016.5258
56. Souza R, Jardim C, Humbert M. Idiopathic pulmonary arterial hypertension. Semin Respir Crit Care Med 2013; 34 (5): 560–7.
57. Young A, Vummidi D, Visovatti S et al. Prevalence, Treatment and Outcomes of Coexistent Pulmonary Hypertension and Interstitial Lung Disease in Systemic Sclerosis. Arthritis Rheumatol 2019. DOI: 10.1002/art.40862
58. Bellando-Randone S, Lepri G, Bruni C et al. Combination therapy with Bosentan and Sildenafil improves Raynaud's phenomenon and fosters the recovery of microvascular involvement in systemic sclerosis. Clin Rheumatol 2016; 35 (1): 127–32.
59. Trombetta AC, Pizzorni C, Ruaro B et al. Effects of Longterm Treatment with Bosentan and Iloprost on Nailfold Absolute Capillary Number, Fingertip Blood Perfusion, and Clinical Status in Systemic Sclerosis. J Rheumatol 2016; 43 (11): 2033–41.
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32. Naert A, De Haes P. Successful treatment with bosentan of lower extremity ulcers in a scleroderma patient. Case Rep Med 2013; 2013: 690591.
33. Hamaguchi Y, Sumida T, Kawaguchi Y. Safety and tolerability of bosentan for digital ulcers in Japanese patients with systemic sclerosis: Prospective, multicenter, open-label study. J Dermatol 2017; 44 (1): 13–7.
34. Matucci-Cerinic M, Denton CP, Furst DE et al. Bosentan treatment of digital ulcers related to systemic sclerosis: results from the RAPIDS-2 randomised, double-blind, placebo-controlled trial. Ann Rheum Dis 2011; 70 (1): 32–8.
35. Nagai Y, Hasegawa M, Hattori T et al. Bosentan for digital ulcers in patients with systemic sclerosis. J Dermatol 2012; 39 (1): 48–51.
36. Baughman RP, Culver DA, Cordova FC et al. Bosentan for sarcoidosis-associated pulmonary hypertension: a double-blind placebo controlled randomized trial. Chest 2014; 145 (4): 810–7.
37. Surie S, Reesink HJ, Marcus JT et al. Clin Bosentan treatment is associated with improvement of right ventricular function and remodeling in chronic thromboembolic pulmonary hypertension. Cardiol 2013; 36 (11): 698–703.
38. Hoeper MM, Madani MM, Nakanishi N et al. Chronic thromboembolic pulmonary hypertension. Lancet Respir Med 2014; 2 (7): 573–82.
39. Nishikawa-Takahashi M, Ueno S, Kario K. Long-term advanced therapy with bosentan improves symptoms and prevents deterioration of inoperable chronic thromboembolic pulmonary hypertension. Life Sci 2014; 118 (2): 410–3.
40. Jaïs X, D'Armini AM, Jansa P et al. Bosentan Effects in iNopErable Forms of chronIc Thromboembolic pulmonary hypertension), a randomized, placebo-controlled trial. J Am Coll Cardiol 2008;
52 (25): 2127–34. DOI: 10.1016/j.jacc.2008.08.059
41. Guo L, Liu YJ, Xie ZL. Safety and tolerability evaluation of oral bosentan in adult congenital heart disease associated pulmonary arterial hypertension: a systematic review and meta-analysis. Eur Rev Med Pharmacol Sci 2014; 18 (5): 638–45.
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43. Maiya S, Hislop AA, Flynn Y, Haworth SG. Response to bosentan in children with pulmonary hypertension. Heart 2006; 92: 664–70.
44. Rosenzweig EB, Ivy DD, Widlitz A et al. Effects of long-term bosentan in children with pulmonary arterial hypertension. J Am Coll Cardiol 2005; 46: 697–704.
45. Mohamed WA, Ismail M. A randomized, double-blind, placebo-controlled, prospective study of bosentan for the treatment of persistent pulmonary hypertension of the newborn. J Perinatol 2012;
32 (8): 608–13.
46. Maneenil G, Thatrimontrichai A, Janjindamai W, Dissaneevate S. Effect of bosentan therapy in persistent pulmonary hypertension of the newborn. Pediatr Neonatol 2018; 59 (1): 58–64.
DOI: 10.1016/j.pedneo.2017.02.003
47. Bolli MN, Boss C, Binkert C et al. The discovery of N-[5-94-bromophenyl0-6-[2-[95-bromo-2-pyrimidinyl) oxy]ethoxy]-4-pyrimidinyl]-N'-propylsulfamide (Macitentan), an orally active, potent dual endothelin receptor antagonist. J Med Chem 2012; 55: 7849–61. DOI: 10.1021/jm3009103
48. Gatfield J, Mueller Grandjean C, Sasse T et al. Slow receptor dissociation kinetics differentiate macitentan from other endothelin receptor antagonists in pulmonary arterial smooth muscle cells. PLoS One 2012; 7 (10): e47662. DOI: 10.1371/journal.pone.0047662
49. Sidharta PN, van Giersbergen PL, Dingemanse J. Safety, tolerability, pharmacokinetics, and pharmacodynamics of macitentan, an endothelin receptor antagonist, in an ascending multiple-dose study in healthy subjects. J Clin Pharmacol 2013; 53 (11): 1131–8. DOI: 10.1002/jcph.152
50. Pulido T, Adzerikho I, Channick RN, et al. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med. 2013; 369 (9): 809–18. DOI: 10.1056/NEJMoa1213917/
51. Channick RN, Delcroix M, Ghofrani HA et al. Effect of macitentan on hospitalizations: results from the SERAPHIN trial. JACC Heart Fail 2015; 3 (1): 1–8. DOI: 10.1016/j.jchf.2014.07.013
52. Simonneau G, Channick RN, Delcroix M et al. Incident and prevalent cohorts with pulmonary arterial hypertension: insight from SERAPHIN. Eur Respir J 2015; 46 (6): 1711–20. DOI: 10.1183/13993003.00364-2015
53. Aypar E, Alehan D, Karagöz T et al. Clinical efficacy and safety of switch from bosentan to macitentan in children and young adults with pulmonary arterial hypertension. Cardiol Young 2018;
28 (4): 542–7. DOI: 10.1017/S1047951117002542
54. Vachiéry JL, Delcroix M, Al-Hiti H et al. Macitentan in pulmonary hypertension due to left ventricular dysfunction. Eur Respir J 2018; 51 (2); pii: 1701886. DOI: 10.1183/13993003.01886-2017
55. Khanna D, Denton CP, Merkel PA et al. Effect of Macitentan on the Development of New Ischemic Digital Ulcers in Patients With Systemic Sclerosis: DUAL-1 and DUAL-2 Randomized Clinical Trials. JAMA 2016; 315 (18): 1975–88. DOI: 10.1001/jama.2016.5258
56. Souza R, Jardim C, Humbert M. Idiopathic pulmonary arterial hypertension. Semin Respir Crit Care Med 2013; 34 (5): 560–7.
57. Young A, Vummidi D, Visovatti S et al. Prevalence, Treatment and Outcomes of Coexistent Pulmonary Hypertension and Interstitial Lung Disease in Systemic Sclerosis. Arthritis Rheumatol 2019. DOI: 10.1002/art.40862
58. Bellando-Randone S, Lepri G, Bruni C et al. Combination therapy with Bosentan and Sildenafil improves Raynaud's phenomenon and fosters the recovery of microvascular involvement in systemic sclerosis. Clin Rheumatol 2016; 35 (1): 127–32.
59. Trombetta AC, Pizzorni C, Ruaro B et al. Effects of Longterm Treatment with Bosentan and Iloprost on Nailfold Absolute Capillary Number, Fingertip Blood Perfusion, and Clinical Status in Systemic Sclerosis. J Rheumatol 2016; 43 (11): 2033–41.
60. https://www.rlsnet.ru/mnn_index_id_3680.htm
61. Stevenson MD, Macdonald FC, Langley J et al. The cost-effectiveness of in the United Kingdom for patients with pulmonary arterial hypertension of WHO functional class III. Value Health 2009; 12 (8): 1100–5. DOI: 10.1111/j.1524-4733.2009.00568
62. Fan CS, H WJ. The cost-utility of bosentan in the treatment of pulmonary arterial hypertension patients. Drug Evaluation 2016; 13 (8): 13–9.
63. Highland KB, Strange C, Mazur J, Simpson KN. Treatment of pulmonary arterial hypertension:
a preliminary decision analysis. Chest 2003; 124 (6): 2087–92.
64. Garin MC, Clark L, Chumney EC et al. Cost-utility of treatments for pulmonary arterial hypertension. Clin Drug Invest 2009; 29 (10): 635–46.
65. You R, Qian X, Tang W et al. Cost Effectiveness of Bosentan for Pulmonary Arterial Hypertension: A Systematic Review. Can Respir J 2018; 2018: 1015239. DOI: 10.1155/2018/1015239
66. Coyle K, Coyle D, Blouin J et al. Cost Effictiveness of First-Line Oral Therapies for Pulmonary Arterial Hypertension: A Modelling Study. Pharmacoeconomics 2016; 34 (5): 509–20. DOI: 10.1007/s40273-015-0366-8
67. Barbieri M, Zamboni W, Pippo L et al. Ambrisentan for the treatment of pulmonary arterial hypertension: a budget impact analysis in the Italian context. Expert Opin Orphan Drugs 2014; 2 (10): 989–97.
68. Dranitsaris G, Mehta S. Oral therapies for the treatment of pulmonary arterial hypertension. Applied Health Economics Health Policy 2009; 7 (1): 43–59.
69. Моисеева О.М., Рудакова А.В. Фармакоэкономические аспекты применения мацитентана при терапии легочной артериальной гипертонии. Терапевтический архив. 2017; 89 (3): 72–7.
[Moiseeva O.M., Rudakova A.V. Farmakoekonomicheskie aspekty primeneniia matsitentana pri terapii legochnoi arterial'noi gipertonii. Therapeutic Archive. 2017; 89 (3): 72–7 (in Russian).]
70. Vadlamudi HC, Yalavarthi PR, Basaveswara Rao MV et al. In vitro characterization studies of self-microemulsified bosentan systems. Drug Dev Ind Pharm 2017; 43 (6): 989–95. DOI: 10.1080/03639045.2017.1287720
71. Giménez VM, Sperandeo N, Faudone S et al. Preparation and characterization of bosentan monohydrate/ε-polycaprolactone nanoparticles obtained by electrospraying. Biotechnol Prog 2019; 35 (2): e2748.
________________________________________________
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59. Trombetta AC, Pizzorni C, Ruaro B et al. Effects of Longterm Treatment with Bosentan and Iloprost on Nailfold Absolute Capillary Number, Fingertip Blood Perfusion, and Clinical Status in Systemic Sclerosis. J Rheumatol 2016; 43 (11): 2033–41.
60. https://www.rlsnet.ru/mnn_index_id_3680.htm
61. Stevenson MD, Macdonald FC, Langley J et al. The cost-effectiveness of in the United Kingdom for patients with pulmonary arterial hypertension of WHO functional class III. Value Health 2009; 12 (8): 1100–5. DOI: 10.1111/j.1524-4733.2009.00568
62. Fan CS, H WJ. The cost-utility of bosentan in the treatment of pulmonary arterial hypertension patients. Drug Evaluation 2016; 13 (8): 13–9.
63. Highland KB, Strange C, Mazur J, Simpson KN. Treatment of pulmonary arterial hypertension:
a preliminary decision analysis. Chest 2003; 124 (6): 2087–92.
64. Garin MC, Clark L, Chumney EC et al. Cost-utility of treatments for pulmonary arterial hypertension. Clin Drug Invest 2009; 29 (10): 635–46.
65. You R, Qian X, Tang W et al. Cost Effectiveness of Bosentan for Pulmonary Arterial Hypertension: A Systematic Review. Can Respir J 2018; 2018: 1015239. DOI: 10.1155/2018/1015239
66. Coyle K, Coyle D, Blouin J et al. Cost Effictiveness of First-Line Oral Therapies for Pulmonary Arterial Hypertension: A Modelling Study. Pharmacoeconomics 2016; 34 (5): 509–20. DOI: 10.1007/s40273-015-0366-8
67. Barbieri M, Zamboni W, Pippo L et al. Ambrisentan for the treatment of pulmonary arterial hypertension: a budget impact analysis in the Italian context. Expert Opin Orphan Drugs 2014; 2 (10): 989–97.
68. Dranitsaris G, Mehta S. Oral therapies for the treatment of pulmonary arterial hypertension. Applied Health Economics Health Policy 2009; 7 (1): 43–59.
69. Moiseeva O.M., Rudakova A.V. Farmakoekonomicheskie aspekty primeneniia matsitentana pri terapii legochnoi arterial'noi gipertonii. Therapeutic Archive. 2017; 89 (3): 72–7 (in Russian).
70. Vadlamudi HC, Yalavarthi PR, Basaveswara Rao MV et al. In vitro characterization studies of self-microemulsified bosentan systems. Drug Dev Ind Pharm 2017; 43 (6): 989–95. DOI: 10.1080/03639045.2017.1287720
71. Giménez VM, Sperandeo N, Faudone S et al. Preparation and characterization of bosentan monohydrate/ε-polycaprolactone nanoparticles obtained by electrospraying. Biotechnol Prog 2019; 35 (2): e2748.
Авторы
Н.А. Шостак, А.А. Клименко, Д.Ю. Андрияшкина*, Н.А. Демидова
ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, Москва, Россия
*andryashkina.darya@yandex.ru
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Цель портала OmniDoctor – предоставление профессиональной информации врачам, провизорам и фармацевтам.