Advertisement

Heart Failure Reviews

, Volume 24, Issue 6, pp 949–965 | Cite as

Advances in targeted therapy for chronic thromboembolic pulmonary hypertension

  • Yi Zhang
  • Xue Yu
  • Qi Jin
  • Qin Luo
  • Zhihui Zhao
  • Qing Zhao
  • Lu Yan
  • Zhihong LiuEmail author
Article

Abstract

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by unresolved thrombi in the pulmonary arteries and microvasculopathy in nonoccluded areas. If left untreated, progressive pulmonary hypertension will induce right heart failure and, finally, death. Currently, pulmonary endarterectomy (PEA) remains the only method that has the potential to cure CTEPH. Unfortunately, up to 40% of patients are ineligible for this procedure for various reasons. In recent years, refined balloon pulmonary angioplasty (BPA) has become an alternative option for inoperable CTEPH patients, and it may be another curative treatment in the future, particularly in combination with prior PEA. Nevertheless, 23% of patients still suffer from persistent PH after BPA. Given that CTEPH shares many similarities with idiopathic pulmonary arterial hypertension (PAH), targeted drugs developed for PAH are also attractive options for CTEPH, especially for inoperable or persistent/recurrent CTEPH patients. To date, riociguat, macitentan, and subcutaneous treprostinil are the only drugs proven by randomized control trials to be capable of improving the exercise capacity (6-min walking distance) of CTEPH patients. In this review, we summarize the achievements and unresolved problems of PAH-targeted therapy for CTEPH over the last decade.

Keywords

Chronic thromboembolic pulmonary hypertension Pulmonary arterial hypertension-targeted therapy Combination therapy Bridging therapy 

Notes

Funding information

This review article was supported by the National Natural Science Foundation of China (81370326, 81641005), Beijing Municipal Science and Technology Project (Z181100001718200), and National Precision Medical Research Program of China (2016YFC0905602).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

References

  1. 1.
    Fedullo P, Kerr KM, Kim NH, Auger WR (2011) Chronic thromboembolic pulmonary hypertension. Am J Respir Crit Care Med 183:1605–1613.  https://doi.org/10.1164/rccm.201011-1854CI CrossRefGoogle Scholar
  2. 2.
    Ende-Verhaar YM, Cannegieter SC, Vonk Noordegraaf A, Delcroix M, Pruszczyk P, Mairuhu AT, Huisman MV, Klok FA (2017) Incidence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: a contemporary view of the published literature. Eur Respir J 49:49.  https://doi.org/10.1183/13993003.01792-2016 CrossRefGoogle Scholar
  3. 3.
    Hoeper MM, Mayer E, Simonneau G, Rubin LJ (2006) Chronic thromboembolic pulmonary hypertension. Circulation 113:2011–2020.  https://doi.org/10.1161/circulationaha.105.602565 CrossRefPubMedGoogle Scholar
  4. 4.
    Lang IM, Madani M (2014) Update on chronic thromboembolic pulmonary hypertension. Circulation 130:508–518.  https://doi.org/10.1161/circulationaha.114.009309 CrossRefGoogle Scholar
  5. 5.
    Galie N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, Simonneau G, Peacock A, Vonk Noordegraaf A, Beghetti M, Ghofrani A, Gomez Sanchez MA, Hansmann G, Klepetko W, Lancellotti P, Matucci M, McDonagh T, Pierard LA, Trindade PT, Zompatori M, Hoeper M (2016) 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 37:67–119.  https://doi.org/10.1093/eurheartj/ehv317 CrossRefPubMedGoogle Scholar
  6. 6.
    Simonneau G, D’Armini AM, Ghofrani HA, Grimminger F, Hoeper MM, Jansa P, Kim NH, Wang C, Wilkins MR, Fritsch A, Davie N, Colorado P, Mayer E (2015) Riociguat for the treatment of chronic thromboembolic pulmonary hypertension: a long-term extension study (CHEST-2). Eur Respir J 45:1293–1302.  https://doi.org/10.1183/09031936.00087114 CrossRefPubMedGoogle Scholar
  7. 7.
    Pesavento R, Prandoni P (2018) Prevention and treatment of the chronic thromboembolic pulmonary hypertension. Thromb Res 164:150–156.  https://doi.org/10.1016/j.thromres.2018.02.149 CrossRefPubMedGoogle Scholar
  8. 8.
    Tanabe N, Kawakami T, Satoh T, Matsubara H, Nakanishi N, Ogino H, Tamura Y, Tsujino I, Ogawa A, Sakao S, Nishizaki M, Ishida K, Ichimura Y, Yoshida M, Tatsumi K (2018) Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension: a systematic review. Respir Investig 56:332–341.  https://doi.org/10.1016/j.resinv.2018.03.004 CrossRefPubMedGoogle Scholar
  9. 9.
    Tsuji A, Ogo T, Ueda J, Fukui S, Morita Y, Fukuda T, Nakanishi N, Ogawa H, Yasuda S (2017) Predictors of residual pulmonary hypertension after balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension. Int J Cardiol 226:118–120.  https://doi.org/10.1016/j.ijcard.2016.09.132 CrossRefPubMedGoogle Scholar
  10. 10.
    Berger G, Azzam ZS, Hardak E, Tavor Y, Yigla M (2011) Idiopathic pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension: can we be certain? Isr Med Assoc J 13:106–110PubMedGoogle Scholar
  11. 11.
    Hoeper MM (2015) Pharmacological therapy for patients with chronic thromboembolic pulmonary hypertension. Eur Respir Rev 24:272–282.  https://doi.org/10.1183/16000617.00001015 CrossRefPubMedGoogle Scholar
  12. 12.
    Matthews DT, Hemnes AR (2016) Current concepts in the pathogenesis of chronic thromboembolic pulmonary hypertension. Pulm Circ 6:145–154.  https://doi.org/10.1086/686011 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Satoh T, Satoh K, Yaoita N, Kikuchi N, Omura J, Kurosawa R, Numano K, Al-Mamun E, Siddique MA, Sunamura S, Nogi M, Suzuki K, Miyata S, Morser J, Shimokawa H (2017) Activated TAFI promotes the development of chronic thromboembolic pulmonary hypertension: a possible novel therapeutic target. Circ Res 120:1246–1262.  https://doi.org/10.1161/circresaha.117.310640 CrossRefPubMedGoogle Scholar
  14. 14.
    Phan K, Jo HE, Xu J, Lau EM (2018) Medical therapy versus balloon angioplasty for CTEPH: a systematic review and meta-analysis. Heart Lung Circ 27:89–98.  https://doi.org/10.1016/j.hlc.2017.01.016 CrossRefPubMedGoogle Scholar
  15. 15.
    Stasch JP, Pacher P, Evgenov OV (2011) Soluble guanylate cyclase as an emerging therapeutic target in cardiopulmonary disease. Circulation 123:2263–2273.  https://doi.org/10.1161/circulationaha.110.981738 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Grimminger F, Weimann G, Frey R, Voswinckel R, Thamm M, Bolkow D, Weissmann N, Muck W, Unger S, Wensing G, Schermuly RT, Ghofrani HA (2009) First acute haemodynamic study of soluble guanylate cyclase stimulator riociguat in pulmonary hypertension. Eur Respir J 33:785–792.  https://doi.org/10.1183/09031936.00039808 CrossRefPubMedGoogle Scholar
  17. 17.
    Ghofrani HA, D’Armini AM, Grimminger F, Hoeper MM, Jansa P, Kim NH, Mayer E, Simonneau G, Wilkins MR, Fritsch A, Neuser D, Weimann G, Wang C (2013) Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med 369:319–329.  https://doi.org/10.1056/NEJMoa1209657 CrossRefPubMedGoogle Scholar
  18. 18.
    McLaughlin VV, Gaine SP, Howard LS, Leuchte HH, Mathier MA, Mehta S, Palazzini M, Park MH, Tapson VF, Sitbon O (2013) Treatment goals of pulmonary hypertension. J Am Coll Cardiol 62:D73–D81.  https://doi.org/10.1016/j.jacc.2013.10.034 CrossRefPubMedGoogle Scholar
  19. 19.
    Nickel N, Golpon H, Greer M, Knudsen L, Olsson K, Westerkamp V, Welte T, Hoeper MM (2012) The prognostic impact of follow-up assessments in patients with idiopathic pulmonary arterial hypertension. Eur Respir J 39:589–596.  https://doi.org/10.1183/09031936.00092311 CrossRefPubMedGoogle Scholar
  20. 20.
    Gabler NB, French B, Strom BL, Palevsky HI, Taichman DB, Kawut SM, Halpern SD (2012) Validation of 6-minute walk distance as a surrogate end point in pulmonary arterial hypertension trials. Circulation 126:349–356.  https://doi.org/10.1161/circulationaha.112.105890 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Jamieson SW, Kapelanski DP, Sakakibara N, Manecke GR, Thistlethwaite PA, Kerr KM, Channick RN, Fedullo PF, Auger WR (2003) Pulmonary endarterectomy: experience and lessons learned in 1,500 cases. Ann Thorac Surg 76:1457–1462 discussion 1462-1454 CrossRefGoogle Scholar
  22. 22.
    D’Armini AM, Ghofrani HA, Kim NH, Mayer E, Morsolini M, Pulido-Zamudio T, Simonneau G, Wilkins MR, Curram J, Davie N, Hoeper MM (2015) Use of responder threshold criteria to evaluate the response to treatment in the phase III CHEST-1 study. J Heart Lung Transplant 34:348–355.  https://doi.org/10.1016/j.healun.2015.02.003 CrossRefGoogle Scholar
  23. 23.
    Simonneau G, D’Armini AM, Ghofrani HA, Grimminger F, Jansa P, Kim NH, Mayer E, Pulido T, Wang C, Colorado P, Fritsch A, Meier C, Nikkho S, Hoeper MM (2016) Predictors of long-term outcomes in patients treated with riociguat for chronic thromboembolic pulmonary hypertension: data from the CHEST-2 open-label, randomised, long-term extension trial. Lancet Respir Med 4:372–380.  https://doi.org/10.1016/s2213-2600(16)30022-4 CrossRefGoogle Scholar
  24. 24.
    Benza RL, Farber HW, Frost A, Grunig E, Hoeper MM, Busse D, Meier C, Nikkho S, Ghofrani HA (2018) REVEAL risk score in patients with chronic thromboembolic pulmonary hypertension receiving riociguat. J Heart Lung Transplant 37:836–843.  https://doi.org/10.1016/j.healun.2018.02.015 CrossRefGoogle Scholar
  25. 25.
    Benza RL, Miller DP, Foreman AJ, Frost AE, Badesch DB, Benton WW, McGoon MD (2015) Prognostic implications of serial risk score assessments in patients with pulmonary arterial hypertension: a Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) analysis. J Heart Lung Transplant 34:356–361.  https://doi.org/10.1016/j.healun.2014.09.016 CrossRefPubMedGoogle Scholar
  26. 26.
    Benza RL, Miller DP, Gomberg-Maitland M, Frantz RP, Foreman AJ, Coffey CS, Frost A, Barst RJ, Badesch DB, Elliott CG, Liou TG, McGoon MD (2010) Predicting survival in pulmonary arterial hypertension: insights from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL). Circulation 122:164–172.  https://doi.org/10.1161/circulationaha.109.898122 CrossRefPubMedGoogle Scholar
  27. 27.
    Benza RL, Miller DP, Barst RJ, Badesch DB, Frost AE, McGoon MD (2012) An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL registry. Chest 142:448–456.  https://doi.org/10.1378/chest.11-1460 CrossRefPubMedGoogle Scholar
  28. 28.
    Halank M, Hoeper MM, Ghofrani HA, Meyer FJ, Stahler G, Behr J, Ewert R, Fletcher M, Colorado P, Nikkho S, Grimminger F (2017) Riociguat for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: results from a phase II long-term extension study. Respir Med 128:50–56.  https://doi.org/10.1016/j.rmed.2017.05.008 CrossRefPubMedGoogle Scholar
  29. 29.
    McLaughlin VV, Jansa P, Nielsen-Kudsk JE, Halank M, Simonneau G, Grunig E, Ulrich S, Rosenkranz S, Gomez Sanchez MA, Pulido T, Pepke-Zaba J, Barbera JA, Hoeper MM, Vachiery JL, Lang I, Carvalho F, Meier C, Mueller K, Nikkho S, D’Armini AM (2017) Riociguat in patients with chronic thromboembolic pulmonary hypertension: results from an early access study. BMC Pulm Med 17:216.  https://doi.org/10.1186/s12890-017-0563-7 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Gall H, Vachiery JL, Tanabe N, Halank M, Orozco-Levi M, Mielniczuk L, Chang M, Vogtlander K, Grunig E (2018) Real-world switching to riociguat: management and practicalities in patients with PAH and CTEPH. Lung 196:305–312.  https://doi.org/10.1007/s00408-018-0100-3 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Hill NS, Rahaghi FF, Sood N, Frey R, Ghofrani HA (2017) Individual dose adjustment of riociguat in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Respir Med 129:124–129.  https://doi.org/10.1016/j.rmed.2017.05.005 CrossRefPubMedGoogle Scholar
  32. 32.
    Frey R, Becker C, Unger S, Schmidt A, Wensing G, Muck W (2016) Assessment of the effects of hepatic impairment and smoking on the pharmacokinetics of a single oral dose of the soluble guanylate cyclase stimulator riociguat (BAY 63-2521). Pulm Circ 6:S5–S14.  https://doi.org/10.1086/685015 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Saleh S, Becker C, Frey R, Muck W (2016) Population pharmacokinetics and the pharmacokinetic/pharmacodynamic relationship of riociguat in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. Pulm Circ 6:S86–S96.  https://doi.org/10.1086/685404 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Frey R, Becker C, Unger S, Schmidt A, Wensing G, Muck W (2016) Assessment of the effects of renal impairment and smoking on the pharmacokinetics of a single oral dose of the soluble guanylate cyclase stimulator riociguat (BAY 63-2521). Pulm Circ 6:S15–S26.  https://doi.org/10.1086/685017 CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Delcroix M, Lang I, Pepke-Zaba J, Jansa P, D’Armini AM, Snijder R, Bresser P, Torbicki A, Mellemkjaer S, Lewczuk J, Simkova I, Barbera JA, de Perrot M, Hoeper MM, Gaine S, Speich R, Gomez-Sanchez MA, Kovacs G, Jais X, Ambroz D, Treacy C, Morsolini M, Jenkins D, Lindner J, Dartevelle P, Mayer E, Simonneau G (2016) Long-term outcome of patients with chronic thromboembolic pulmonary hypertension: results from an international prospective registry. Circulation 133:859–871.  https://doi.org/10.1161/circulationaha.115.016522 CrossRefPubMedGoogle Scholar
  36. 36.
    Pepke-Zaba J, Delcroix M, Lang I, Mayer E, Jansa P, Ambroz D, Treacy C, D’Armini AM, Morsolini M, Snijder R, Bresser P, Torbicki A, Kristensen B, Lewczuk J, Simkova I, Barbera JA, de Perrot M, Hoeper MM, Gaine S, Speich R, Gomez-Sanchez MA, Kovacs G, Hamid AM, Jais X, Simonneau G (2011) Chronic thromboembolic pulmonary hypertension (CTEPH): results from an international prospective registry. Circulation 124:1973–1981.  https://doi.org/10.1161/circulationaha.110.015008 CrossRefGoogle Scholar
  37. 37.
    Marra AM, Egenlauf B, Ehlken N, Fischer C, Eichstaedt C, Nagel C, Bossone E, Cittadini A, Halank M, Gall H, Olsson KM, Lange TJ, Grunig E (2015) Change of right heart size and function by long-term therapy with riociguat in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Int J Cardiol 195:19–26.  https://doi.org/10.1016/j.ijcard.2015.05.105 CrossRefGoogle Scholar
  38. 38.
    Ahmadi A, Thornhill RE, Pena E, Renaud JM, Promislow S, Chandy G, Davies RA, Stewart DJ, Contreras-Dominguez V, Dunne R, Doyle-Cox C, Beanlands RS, deKemp RA, Mielniczuk LM (2018) Effects of riociguat on right ventricular remodelling in chronic thromboembolic pulmonary hypertension patients: a prospective study. Can J Cardiol 34:1137–1144.  https://doi.org/10.1016/j.cjca.2018.06.007 CrossRefGoogle Scholar
  39. 39.
    Weir NA, Conrey A, Lewis D, Mehari A (2018) Riociguat use in sickle cell related chronic thromboembolic pulmonary hypertension: a case series. Pulm Circ 8:2045894018791802.  https://doi.org/10.1177/2045894018791802 CrossRefGoogle Scholar
  40. 40.
    Ahn HS, Foster M, Cable M, Pitts BJ, Sybertz EJ (1991) Ca/CaM-stimulated and cGMP-specific phosphodiesterases in vascular and non-vascular tissues. Adv Exp Med Biol 308:191–197CrossRefGoogle Scholar
  41. 41.
    Suntharalingam J, Hughes RJ, Goldsmith K, Doughty N, George P, Toshner M, Sheares KK, Pepke-Zaba J (2007) Acute haemodynamic responses to inhaled nitric oxide and intravenous sildenafil in distal chronic thromboembolic pulmonary hypertension (CTEPH). Vasc Pharmacol 46:449–455.  https://doi.org/10.1016/j.vph.2007.01.008 CrossRefGoogle Scholar
  42. 42.
    Reichenberger F, Voswinckel R, Enke B, Rutsch M, El Fechtali E, Schmehl T, Olschewski H, Schermuly R, Weissmann N, Ghofrani HA, Grimminger F, Mayer E, Seeger W (2007) Long-term treatment with sildenafil in chronic thromboembolic pulmonary hypertension. Eur Respir J 30:922–927.  https://doi.org/10.1183/09031936.00039007 CrossRefPubMedGoogle Scholar
  43. 43.
    Suntharalingam J, Treacy CM, Doughty NJ, Goldsmith K, Soon E, Toshner MR, Sheares KK, Hughes R, Morrell NW, Pepke-Zaba J (2008) Long-term use of sildenafil in inoperable chronic thromboembolic pulmonary hypertension. Chest 134:229–236.  https://doi.org/10.1378/chest.07-2681 CrossRefPubMedGoogle Scholar
  44. 44.
    Toshner MR, Gopalan D, Suntharalingam J, Treacy C, Soon E, Sheares KK, Morrell NW, Screaton N, Pepke-Zaba J (2010) Pulmonary arterial size and response to sildenafil in chronic thromboembolic pulmonary hypertension. J Heart Lung Transplant 29:610–615.  https://doi.org/10.1016/j.healun.2009.12.014 CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Sekine A, Tanabe N, Sugiura T, Shigeta A, Jujo T, Nishimura R, Sakao S, Kasahara Y, Tatsumi K (2014) Polymorphism of the G protein beta3 subunit gene influences the efficacy of sildenafil in patients with pulmonary hypertension. Intern Med 53:291–297CrossRefGoogle Scholar
  46. 46.
    Nishimura R, Tanabe N, Sekine A, Kasai H, Suda R, Kato F, Jujo T, Sugiura T, Shigeta A, Sakao S, Tatsumi K (2016) Synergistic effects of ACE insertion/deletion and GNB3 C825T polymorphisms on the efficacy of PDE-5 inhibitor in patients with pulmonary hypertension. Respiration 91:132–140.  https://doi.org/10.1159/000443772 CrossRefPubMedGoogle Scholar
  47. 47.
    Claessen G, La Gerche A, Wielandts JY, Bogaert J, Van Cleemput J, Wuyts W, Claus P, Delcroix M, Heidbuchel H (2015) Exercise pathophysiology and sildenafil effects in chronic thromboembolic pulmonary hypertension. Heart 101:637–644.  https://doi.org/10.1136/heartjnl-2014-306851 CrossRefPubMedGoogle Scholar
  48. 48.
    Yamamura A, Fujitomi E, Ohara N, Tsukamoto K, Sato M, Yamamura H (2017) Tadalafil induces antiproliferation, apoptosis, and phosphodiesterase type 5 downregulation in idiopathic pulmonary arterial hypertension in vitro. Eur J Pharmacol 810:44–50.  https://doi.org/10.1016/j.ejphar.2017.06.010 CrossRefPubMedGoogle Scholar
  49. 49.
    Southwood M, MacKenzie Ross RV, Kuc RE, Hagan G, Sheares KK, Jenkins DP, Goddard M, Davenport AP, Pepke-Zaba J (2016) Endothelin ETA receptors predominate in chronic thromboembolic pulmonary hypertension. Life Sci 159:104–110.  https://doi.org/10.1016/j.lfs.2016.02.036 CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Reesink HJ, Meijer RC, Lutter R, Boomsma F, Jansen HM, Kloek JJ, Bresser P (2006) Hemodynamic and clinical correlates of endothelin-1 in chronic thromboembolic pulmonary hypertension. Circ J 70:1058–1063CrossRefGoogle Scholar
  51. 51.
    Bauer M, Wilkens H, Langer F, Schneider SO, Lausberg H, Schafers HJ (2002) Selective upregulation of endothelin B receptor gene expression in severe pulmonary hypertension. Circulation 105:1034–1036CrossRefGoogle Scholar
  52. 52.
    Jais X, D’Armini AM, Jansa P, Torbicki A, Delcroix M, Ghofrani HA, Hoeper MM, Lang IM, Mayer E, Pepke-Zaba J, Perchenet L, Morganti A, Simonneau G, Rubin LJ (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.  https://doi.org/10.1016/j.jacc.2008.08.059 CrossRefPubMedGoogle Scholar
  53. 53.
    Nishikawa-Takahashi M, Ueno S, Kario K (2014) Long-term advanced therapy with bosentan improves symptoms and prevents deterioration of inoperable chronic thromboembolic pulmonary hypertension. Life Sci 118:410–413.  https://doi.org/10.1016/j.lfs.2014.03.024 CrossRefPubMedGoogle Scholar
  54. 54.
    Post MC, Plokker HW, Kelder JC, Snijder RJ (2009) Long-term efficacy of bosentan in inoperable chronic thromboembolic pulmonary hypertension. Neth Hear J 17:329–333CrossRefGoogle Scholar
  55. 55.
    Ulrich S, Speich R, Domenighetti G, Geiser T, Aubert JD, Rochat T, Huber L, Treder U, Fischler M (2007) Bosentan therapy for chronic thromboembolic pulmonary hypertension. A national open label study assessing the effect of bosentan on haemodynamics, exercise capacity, quality of life, safety and tolerability in patients with chronic thromboembolic pulmonary hypertension (BOCTEPH-study). Swiss Med Wkly 137:573–580PubMedGoogle Scholar
  56. 56.
    Vassallo FG, Kodric M, Scarduelli C, Harari S, Potena A, Scarda A, Piattella M, Cassandro R, Confalonieri M (2009) Bosentan for patients with chronic thromboembolic pulmonary hypertension. Eur J Intern Med 20:24–29.  https://doi.org/10.1016/j.ejim.2008.03.008 CrossRefPubMedGoogle Scholar
  57. 57.
    Becattini C, Manina G, Busti C, Gennarini S, Agnelli G (2010) Bosentan for chronic thromboembolic pulmonary hypertension: findings from a systematic review and meta-analysis. Thromb Res 126:e51–e56.  https://doi.org/10.1016/j.thromres.2010.01.007 CrossRefPubMedGoogle Scholar
  58. 58.
    Chen X, Zhai Z, Huang K, Xie W, Wan J, Wang C (2018) Bosentan therapy for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: a systemic review and meta-analysis. Clin Respir J 12:2065–2074.  https://doi.org/10.1111/crj.12774 CrossRefPubMedGoogle Scholar
  59. 59.
    Hirashiki A, Adachi S, Nakano Y, Kamimura Y, Shimokata S, Takeshita K, Murohara T, Kondo T (2016) Effects of bosentan on peripheral endothelial function in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. Pulm Circ 6:168–173.  https://doi.org/10.1086/685715 CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Gatfield J, Mueller Grandjean C, Sasse T, Clozel M, Nayler O (2012) Slow receptor dissociation kinetics differentiate macitentan from other endothelin receptor antagonists in pulmonary arterial smooth muscle cells. PLoS One 7:e47662.  https://doi.org/10.1371/journal.pone.0047662 CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Ghofrani HA, Simonneau G, D’Armini AM, Fedullo P, Howard LS, Jais X, Jenkins DP, Jing ZC, Madani MM, Martin N, Mayer E, Papadakis K, Richard D, Kim NH (2017) Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study. Lancet Respir Med 5:785–794.  https://doi.org/10.1016/s2213-2600(17)30305-3 CrossRefPubMedGoogle Scholar
  62. 62.
    Clapp LH, Gurung R (2015) The mechanistic basis of prostacyclin and its stable analogues in pulmonary arterial hypertension: role of membrane versus nuclear receptors. Prostaglandins Other Lipid Mediat 120:56–71.  https://doi.org/10.1016/j.prostaglandins.2015.04.007 CrossRefPubMedGoogle Scholar
  63. 63.
    Scelsi L, Ghio S, Campana C, D’Armini AM, Serio A, Klersy C, Piovella F, Vigano M, Tavazzi L (2004) Epoprostenol in chronic thromboembolic pulmonary hypertension with distal lesions. Ital Heart J 5:618–623PubMedGoogle Scholar
  64. 64.
    Cabrol S, Souza R, Jais X, Fadel E, Ali RH, Humbert M, Dartevelle P, Simonneau G, Sitbon O (2007) Intravenous epoprostenol in inoperable chronic thromboembolic pulmonary hypertension. J Heart Lung Transplant 26:357–362.  https://doi.org/10.1016/j.healun.2006.12.014 CrossRefPubMedGoogle Scholar
  65. 65.
    Ikari J, Tanabe N, Tatsuno I, Yamanaka M, Sakao S, Tada Y, Kurosu K, Kasahara Y, Takiguchi Y, Tatsumi K (2011) ACTH deficiency and PGI(2) therapy in chronic thromboembolic pulmonary hypertension. Int J Cardiol 146:449–450.  https://doi.org/10.1016/j.ijcard.2010.10.115 CrossRefPubMedGoogle Scholar
  66. 66.
    Olschewski H, Simonneau G, Galie N, Higenbottam T, Naeije R, Rubin LJ, Nikkho S, Speich R, Hoeper MM, Behr J, Winkler J, Sitbon O, Popov W, Ghofrani HA, Manes A, Kiely DG, Ewert R, Meyer A, Corris PA, Delcroix M, Gomez-Sanchez M, Siedentop H, Seeger W (2002) Inhaled iloprost for severe pulmonary hypertension. N Engl J Med 347:322–329.  https://doi.org/10.1056/NEJMoa020204 CrossRefPubMedGoogle Scholar
  67. 67.
    Krug S, Hammerschmidt S, Pankau H, Wirtz H, Seyfarth HJ (2008) Acute improved hemodynamics following inhaled iloprost in chronic thromboembolic pulmonary hypertension. Respiration 76:154–159.  https://doi.org/10.1159/000107977 CrossRefPubMedGoogle Scholar
  68. 68.
    Ulrich S, Fischler M, Speich R, Popov V, Maggiorini M (2006) Chronic thromboembolic and pulmonary arterial hypertension share acute vasoreactivity properties. Chest 130:841–846.  https://doi.org/10.1378/chest.130.3.841 CrossRefPubMedGoogle Scholar
  69. 69.
    Reichenberger F, Mainwood A, Doughty N, Fineberg A, Morrell NW, Pepke-Zaba J (2007) Effects of nebulised iloprost on pulmonary function and gas exchange in severe pulmonary hypertension. Respir Med 101:217–222.  https://doi.org/10.1016/j.rmed.2006.05.019 CrossRefPubMedGoogle Scholar
  70. 70.
    Lang I, Gomez-Sanchez M, Kneussl M, Naeije R, Escribano P, Skoro-Sajer N, Vachiery JL (2006) Efficacy of long-term subcutaneous treprostinil sodium therapy in pulmonary hypertension. Chest 129:1636–1643.  https://doi.org/10.1378/chest.129.6.1636 CrossRefPubMedGoogle Scholar
  71. 71.
    Skoro-Sajer N, Bonderman D, Wiesbauer F, Harja E, Jakowitsch J, Klepetko W, Kneussl MP, Lang IM (2007) Treprostinil for severe inoperable chronic thromboembolic pulmonary hypertension. J Thromb Haemost 5:483–489.  https://doi.org/10.1111/j.1538-7836.2007.02394.x CrossRefPubMedGoogle Scholar
  72. 72.
    Sadushi-Kolici R, Jansa P, Kopec G, Torbicki A, Skoro-Sajer N, Campean IA, Halank M, Simkova I, Karlocai K, Steringer-Mascherbauer R, Samarzija M, Salobir B, Klepetko W, Lindner J, Lang IM (2019) Subcutaneous treprostinil for the treatment of severe non-operable chronic thromboembolic pulmonary hypertension (CTREPH): a double-blind, phase 3, randomised controlled trial. Lancet Respir Med 7:239–248.  https://doi.org/10.1016/s2213-2600(18)30367-9 CrossRefPubMedGoogle Scholar
  73. 73.
    Ono F, Nagaya N, Okumura H, Shimizu Y, Kyotani S, Nakanishi N, Miyatake K (2003) Effect of orally active prostacyclin analogue on survival in patients with chronic thromboembolic pulmonary hypertension without major vessel obstruction. Chest 123:1583–1588CrossRefGoogle Scholar
  74. 74.
    Nagaya N, Shimizu Y, Satoh T, Oya H, Uematsu M, Kyotani S, Sakamaki F, Sato N, Nakanishi N, Miyatake K (2002) Oral beraprost sodium improves exercise capacity and ventilatory efficiency in patients with primary or thromboembolic pulmonary hypertension. Heart 87:340–345CrossRefGoogle Scholar
  75. 75.
    Vizza CD, Badagliacca R, Sciomer S, Poscia R, Battagliese A, Schina M, Agati L, Fedele F (2006) Mid-term efficacy of beraprost, an oral prostacyclin analog, in the treatment of distal CTEPH: a case control study. Cardiology 106:168–173.  https://doi.org/10.1159/000092920 CrossRefPubMedGoogle Scholar
  76. 76.
    Holmboe S, Andersen A, Jensen RV, Kimose HH, Ilkjaer LB, Shen L, Clapp LH, Nielsen-Kudsk JE (2017) Prostacyclins have no direct inotropic effect on isolated atrial strips from the normal and pressure-overloaded human right heart. Pulm Circ 7:339–347.  https://doi.org/10.1177/2045893217691532 CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Sitbon O, Channick R, Chin KM, Frey A, Gaine S, Galie N, Ghofrani HA, Hoeper MM, Lang IM, Preiss R, Rubin LJ, Di Scala L, Tapson V, Adzerikho I, Liu J, Moiseeva O, Zeng X, Simonneau G, McLaughlin VV (2015) Selexipag for the treatment of pulmonary arterial hypertension. N Engl J Med 373:2522–2533.  https://doi.org/10.1056/NEJMoa1503184 CrossRefPubMedGoogle Scholar
  78. 78.
    Thurber KM, Williams BM, Bates RE, Frantz RP (2017) Transition of intravenous treprostinil to oral therapy in a patient with functional class IV chronic thromboembolic pulmonary hypertension. Pharmacotherapy 37:e76–e81.  https://doi.org/10.1002/phar.1951 CrossRefPubMedGoogle Scholar
  79. 79.
    Gall H, Preston IR, Hinzmann B, Heinz S, Jenkins D, Kim NH, Lang I (2016) An international physician survey of chronic thromboembolic pulmonary hypertension management. Pulm Circ 6:472–482.  https://doi.org/10.1086/688084 CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Ghofrani HA, Wiedemann R, Rose F, Olschewski H, Schermuly RT, Weissmann N, Seeger W, Grimminger F (2002) Combination therapy with oral sildenafil and inhaled iloprost for severe pulmonary hypertension. Ann Intern Med 136:515–522CrossRefGoogle Scholar
  81. 81.
    Voswinckel R, Reichenberger F, Enke B, Kreckel A, Krick S, Gall H, Schermuly RT, Grimminger F, Rubin LJ, Olschewski H, Seeger W, Ghofrani HA (2008) Acute effects of the combination of sildenafil and inhaled treprostinil on haemodynamics and gas exchange in pulmonary hypertension. Pulm Pharmacol Ther 21:824–832.  https://doi.org/10.1016/j.pupt.2008.07.003 CrossRefPubMedGoogle Scholar
  82. 82.
    Horng M, Mohammad I, Smith ZR, Awdish RL, Cajigas HR (2016) Inhaled iloprost for chronic thromboembolic pulmonary hypertension (CTEPH) during pregnancy: a case report. Pharmacotherapy 36(9):e142–e147.  https://doi.org/10.1002/phar.1793 CrossRefPubMedGoogle Scholar
  83. 83.
    Swisher JW, Elliott D (2017) Combination therapy with riociquat and inhaled treprostinil in inoperable and progressive chronic thromboembolic pulmonary hypertension. Respir Med Case Rep 20:45–47.  https://doi.org/10.1016/j.rmcr.2016.11.012 CrossRefPubMedGoogle Scholar
  84. 84.
    Tromeur C, Jais X, Mercier O, Couturaud F, Montani D, Savale L, Jevnikar M, Weatherald J, Sitbon O, Parent F, Fabre D, Mussot S, Dartevelle P, Humbert M, Simonneau G, Fadel E (2018) Factors predicting outcome after pulmonary endarterectomy. PLoS One 13:e0198198.  https://doi.org/10.1371/journal.pone.0198198 CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Nagaya N, Sasaki N, Ando M, Ogino H, Sakamaki F, Kyotani S, Nakanishi N (2003) Prostacyclin therapy before pulmonary thromboendarterectomy in patients with chronic thromboembolic pulmonary hypertension. Chest 123:338–343CrossRefGoogle Scholar
  86. 86.
    Reesink HJ, Surie S, Kloek JJ, Tan HL, Tepaske R, Fedullo PF, Bresser P (2010) Bosentan as a bridge to pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension. J Thorac Cardiovasc Surg 139:85–91.  https://doi.org/10.1016/j.jtcvs.2009.03.053 CrossRefPubMedGoogle Scholar
  87. 87.
    Surie S, Reesink HJ, Marcus JT, van der Plas MN, Kloek JJ, Vonk-Noordegraaf A, Bresser P (2013) Bosentan treatment is associated with improvement of right ventricular function and remodeling in chronic thromboembolic pulmonary hypertension. Clin Cardiol 36:698–703.  https://doi.org/10.1002/clc.22197 CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Kramm T, Eberle B, Krummenauer F, Guth S, Oelert H, Mayer E (2003) Inhaled iloprost in patients with chronic thromboembolic pulmonary hypertension: effects before and after pulmonary thromboendarterectomy. Ann Thorac Surg 76:711–718CrossRefGoogle Scholar
  89. 89.
    Jensen KW, Kerr KM, Fedullo PF, Kim NH, Test VJ, Ben-Yehuda O, Auger WR (2009) Pulmonary hypertensive medical therapy in chronic thromboembolic pulmonary hypertension before pulmonary thromboendarterectomy. Circulation 120:1248–1254.  https://doi.org/10.1161/circulationaha.109.865881 CrossRefPubMedGoogle Scholar
  90. 90.
    Charalampopoulos A, Gibbs JS, Davies RJ, Gin-Sing W, Murphy K, Sheares KK, Pepke-Zaba J, Jenkins DP, Howard LS (2016) Exercise physiological responses to drug treatments in chronic thromboembolic pulmonary hypertension. J Appl Physiol 121:623–628.  https://doi.org/10.1152/japplphysiol.00087.2016 CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Inami T, Kataoka M, Shimura N, Ishiguro H, Yanagisawa R, Taguchi H, Fukuda K, Yoshino H, Satoh T (2013) Pulmonary edema predictive scoring index (PEPSI), a new index to predict risk of reperfusion pulmonary edema and improvement of hemodynamics in percutaneous transluminal pulmonary angioplasty. JACC Cardiovasc Interv 6:725–736.  https://doi.org/10.1016/j.jcin.2013.03.009 CrossRefPubMedGoogle Scholar
  92. 92.
    Inami T, Kataoka M, Shimura N, Ishiguro H, Yanagisawa R, Fukuda K, Yoshino H, Satoh T (2014) Pressure-wire-guided percutaneous transluminal pulmonary angioplasty: a breakthrough in catheter-interventional therapy for chronic thromboembolic pulmonary hypertension. JACC Cardiovasc Interv 7:1297–1306.  https://doi.org/10.1016/j.jcin.2014.06.010 CrossRefPubMedGoogle Scholar
  93. 93.
    Feinstein JA, Goldhaber SZ, Lock JE, Ferndandes SM, Landzberg MJ (2001) Balloon pulmonary angioplasty for treatment of chronic thromboembolic pulmonary hypertension. Circulation 103:10–13CrossRefGoogle Scholar
  94. 94.
    Mizoguchi H, Ogawa A, Munemasa M, Mikouchi H, Ito H, Matsubara H (2012) Refined balloon pulmonary angioplasty for inoperable patients with chronic thromboembolic pulmonary hypertension. Circ Cardiovasc Interv 5:748–755.  https://doi.org/10.1161/circinterventions.112.971077 CrossRefPubMedGoogle Scholar
  95. 95.
    Sugimura K, Fukumoto Y, Satoh K, Nochioka K, Miura Y, Aoki T, Tatebe S, Miyamichi-Yamamoto S, Shimokawa H (2012) Percutaneous transluminal pulmonary angioplasty markedly improves pulmonary hemodynamics and long-term prognosis in patients with chronic thromboembolic pulmonary hypertension. Circ J 76:485–488CrossRefGoogle Scholar
  96. 96.
    Galie N, Olschewski H, Oudiz RJ, Torres F, Frost A, Ghofrani HA, Badesch DB, McGoon MD, McLaughlin VV, Roecker EB, Gerber MJ, Dufton C, Wiens BL, Rubin LJ (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.  https://doi.org/10.1161/circulationaha.107.742510 CrossRefPubMedGoogle Scholar
  97. 97.
    Divers C, Platt D, Wang E, Lin J, Lingohr-Smith M, Mathai SC (2017) A review of clinical trial endpoints of patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension and how they relate to patient outcomes in the United States. J Manag Care Spec Pharm 23:92–104.  https://doi.org/10.18553/jmcp.2017.23.1.92 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Yi Zhang
    • 1
  • Xue Yu
    • 1
  • Qi Jin
    • 1
  • Qin Luo
    • 1
  • Zhihui Zhao
    • 1
  • Qing Zhao
    • 1
  • Lu Yan
    • 1
  • Zhihong Liu
    • 1
    Email author
  1. 1.Center for Pulmonary Vascular Diseases, Fuwai Hospital, National Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Personalised recommendations