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01-12-2019 | Bosentan | PULMONARY HYPERTENSION

Bosentan or Macitentan Therapy in Chronic Thromboembolic Pulmonary Hypertension?

Authors: M. C. J. van Thor, L. ten Klooster, R. J. Snijder, J. C. Kelder, J. J. Mager, M. C. Post

Published in: Lung | Issue 6/2019

Abstract

Objective

Research comparing bosentan and macitentan in chronic thromboembolic pulmonary hypertension (CTEPH) is scarce, although macitentan might have superior pharmacologic properties. We present the first real-world, 2-year follow-up results and compare clinical outcomes of both drugs in CTEPH.

Methods

All consecutive, technical inoperable or residual CTEPH patients receiving bosentan or macitentan, diagnosed in our multidisciplinary team between January 2003 and January 2019, were included. We report and compare survival, clinical worsening (CW), adverse events, WHO FC, NT-proBNP and 6-min walking test (6MWT) until 2 years after medication initiation.

Results

In total, 112 patients receiving bosentan or macitentan (58% female, mean age 62 ± 14 years, 68% WHO FC III/IV, 51% bosentan) could be included. Mean treatment duration was 1.9 ± 0.4 years for bosentan and 1.2 ± 0.6 years for macitentan. Two-year survival rate was 91% for bosentan and 80% for macitentan (HR mortality macitentan 1.85 [0.56–6.10], p = 0.31). Two-year CW-free survival was 81% and 58%, respectively (HR CW macitentan 2.16 [0.962–4.87], p = 0.06). Right atrial pressure, cardiac output (for mortality alone) and 6MWT lowest saturation were multivariate predictors at baseline. Overall adverse event rates were comparable and WHO FC, NT-proBNP and 6MWT distance improved similar for both drugs till 2-year follow-up.

Conclusion

CTEPH patients receiving bosentan or macitentan have improved clinical outcomes till 2-year follow-up, without significant differences in outcomes between both therapies.

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Simonneau G, Torbicki A, Dorfmüller P, Kim N (2017) The pathophysiology of chronic thromboembolic pulmonary hypertension. Eur Respir Rev 26:160112. https://doi.org/10.1183/16000617.0112-2016 CrossRefPubMed

Jenkins D, Madani M, Fadel E, D'Armini AM, Mayer E (2017) Pulmonary endarterectomy in the management of chronic thromboembolic pulmonary hypertension. Eur Respir Rev 26:160111. https://doi.org/10.1183/16000617.0111-2016 CrossRefPubMed

Galiè N, Humbert M, Vachiery JL, ESC Scientific Document Group et al (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 CrossRefPubMed

Ghofrani HA, D'Armini AM, Grimminger F, CHEST-1 Study Group et al (2013) Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med 369:319–329. https://doi.org/10.1056/NEJMoa1209657 CrossRefPubMed

Simonneau G, D'Armini AM, Ghofrani HA et al (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 CrossRefPubMed

van Thor MCJ, Ten Klooster L, Snijder RJ, Post MC, Mager JJ (2019) Long-term clinical value and outcome of riociguat in chronic thromboembolic pulmonary hypertension. Int J Cardiol Heart Vasc 22:163–168. https://doi.org/10.1016/j.ijcha.2019.02.004 CrossRefPubMedPubMedCentral

Kim NH, Delcroix M, Jais X et al (2019) Chronic thromboembolic pulmonary hypertension. Eur Respir J. 53(1):1801915. https://doi.org/10.1183/13993003.01915-2018 CrossRefPubMedPubMedCentral

Jaïs 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. https://doi.org/10.1016/j.jacc.2008.08.059 CrossRefPubMed

Ghofrani HA, Simonneau G, D'Armini AM, MERIT study investigators et al (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 CrossRefPubMed

10.

Iglarz M, Bossu A, Wanner D et al (2014) Comparison of pharmacological activity of macitentan and bosentan in preclinical models of systemic and pulmonary hypertension. Life Sci 118:333–339. https://doi.org/10.1016/j.lfs.2014.02.018 CrossRefPubMed

11.

Khadka A, Singh Brashier DB, Tejus A, Sharma AK (2015) Macitentan: An important addition to the treatment of pulmonary arterial hypertension. J Pharmacol Pharmacother 6:53–57. https://doi.org/10.4103/0976-500X.149151 CrossRefPubMedPubMedCentral

12.

Boss C, Bolli MH, Gatfield J (2016) From bosentan (Tracleer®) to macitentan (Opsumit®): the medicinal chemistry perspective. Bioorg Med Chem Lett 26:3381–3394. https://doi.org/10.1016/j.bmcl.2016.06.014 CrossRefPubMed

13.

Rich S, Rubin LJ, Abenhail L et al (1998) Executive summary from the world symposium on primary pulmonary hypertension (Evian, France, September 6–10, 1998). The World Health Organization publication via the Internet. https://www.who.int/ncd/cvd/pph.html

14.

Delcroix M, Staehler G, Gall H (2018) Risk assessment in medically treated chronic thromboembolic pulmonary hypertension patients. Eur Respir J 52:1800248CrossRefPubMed

15.

Lang I, Meyer BC, Ogo T et al (2017) Balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension. Eur Respir Rev 26:160119. https://doi.org/10.1183/16000617.0119-2016 CrossRefPubMed

16.

Aypar E, Alehan D, Karagöz T, Aykan HH, Ertugrul İ (2018) Clinical efficacy and safety of switch from bosentan to macitentan in children and young adults with pulmonary arterial hypertension. Cardiol Young 28:542–547. https://doi.org/10.1017/S1047951117002542 CrossRefPubMed

17.

Safdar Z, Thakur A, Frost A (2017) Tolerability of switch to macitentan from bosentan in pulmonary arterial hypertension. South Med J 110:223–228. https://doi.org/10.14423/SMJ.0000000000000607 CrossRefPubMed

18.

Blok IM, van Riel ACMJ, van Dijk APJ, Mulder BJM, Bouma BJ (2017) From bosentan to macitentan for pulmonary arterial hypertension and adult congenital heart disease: further improvement?. Int J Cardiol 227:51–52. https://doi.org/10.1016/j.ijcard.2016.11.211 CrossRefPubMed

19.

Delcroix M, Lang I, Pepke-Zaba J et al (2016) Long-term outcome of patients with chronic thromboembolic pulmonary hypertension: results from an international prospective registry. Circulation 133:859–871CrossRefPubMed

20.

Hughes RJ, Jais X, Bonderman D et al (2006) The efficacy of bosentan in inoperable chronic thromboembolic pulmonary hypertension: a 1-year follow-up study. Eur Respir J 28(1):138–143CrossRefPubMed

21.

Ulrich S, Speich R, Domenighetti G et al (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(41–42):573–580PubMed

22.

Vassallo FG, Kodric M, Scarduelli C et al (2009) Bosentan for patients with chronic thromboembolic pulmonary hypertension. Eur J Intern Med 20(1):24–29CrossRefPubMed

23.

Reesink HJ, Surie S, Kloek JJ et al (2010) Bosentan as a bridge to pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension. J Thorac Cardiovasc Surg 139(1):85–91CrossRefPubMed

24.

Schiess R, Senn O, Fischler M et al (2010) Tobacco smoke: a risk factor for pulmonary arterial hypertension? A case-control study. Chest 138:1086–1092. https://doi.org/10.1378/chest.09-2962 CrossRefPubMed

25.

Guglin M, Kolli S, Chen R (2012) Determinants of pulmonary hypertension in young adults. Int J Clin Pract Suppl 177:13–19. https://doi.org/10.1111/ijcp.12008 CrossRef

26.

Keusch S, Hildenbrand FF, Bollmann T et al (2014) Tobacco smoke exposure in pulmonary arterial and thromboembolic pulmonary hypertension. Respiration 88:38–45. https://doi.org/10.1159/000359972 CrossRefPubMed

27.

Suntharalingam J, Goldsmith K, Toshner M et al (2007) Role of NT-proBNP and 6MWD in chronic thromboembolic pulmonary hypertension. Respir Med 101:2254–2262CrossRefPubMed

28.

Raymond RJ, Hinderliter AL, Willis PW et al (2002) Echocardiographic predictors of adverse outcomes in primary pulmonary hypertension. J Am Coll Cardiol 39:1214–1219CrossRefPubMed

29.

Benza RL, Gomberg-Maitland M, Miller DP et al (2012) The REVEAL Registry risk score calculator in patients newly diagnosed with pulmonary arterial hypertension. Chest 141:354–362. https://doi.org/10.1378/chest.11-0676 CrossRefPubMed

30.

Fares WH, Bellumkonda L, Tonelli AR et al (2016) Right atrial pressure/pulmonary artery wedge pressure ratio: a more specific predictor of survival in pulmonary arterial hypertension. J Heart Lung Transplant 35:760–767. https://doi.org/10.1016/j.healun.2015.12.028 CrossRefPubMed

31.

Tromeur C, Jaïs X, Mercier O et al (2018) Factors predicting outcome after pulmonary endarterectomy. PLoS ONE 13:e0198198. https://doi.org/10.1371/journal.pone.0198198 CrossRefPubMedPubMedCentral

32.

Nierlich P, Hold A, Ristl R (2016) Outcome after surgical treatment of chronic thromboembolic pulmonary hypertension: dealing with different patient subsets. A single-centre experience. Eur J Cardiothorac Surg 50:898–906CrossRefPubMed

33.

Paciocco G, Martinez FJ, Bossone E, Pielsticker E, Gillespie B, Rubenfire M (2001) Oxygen desaturation on the six-minute walk test and mortality in untreated primary pulmonary hypertension. Eur Respir J 17:647–652CrossRefPubMed

34.

Inagaki T, Terada J, Yahaba M et al (2018) Heart rate and oxygen saturation change patterns during 6-min walk test in subjects with chronic thromboembolic pulmonary hypertension. Respir Care 63:573–583. https://doi.org/10.4187/respcare.05788 CrossRefPubMed

35.

Lajoie AC, Lauzière G, Lega JC et al (2016) Combination therapy versus monotherapy for pulmonary arterial hypertension: a meta-analysis. Lancet Respir Med 4:291–305. https://doi.org/10.1016/S2213-2600(16)00027-8 CrossRefPubMed

36.

Fox BD, Shtraichman O, Langleben D, Shimony A, Kramer MR (2016) Combination therapy for pulmonary arterial hypertension: a systematic review and meta-analysis. Can J Cardiol 32:1520–1530. https://doi.org/10.1016/j.cjca.2016.03.004 CrossRefPubMed

37.

Ghofrani HA, Humbert M (2014) The role of combination therapy in managing pulmonary arterial hypertension. Eur Respir Rev 23:469–475. https://doi.org/10.1183/09059180.00007314 CrossRefPubMed

38.

Lajoie AC, Bonnet S, Provencher S (2017) Combination therapy in pulmonary arterial hypertension: recent accomplishments and future challenges. Pulm Circ 7:312–325. https://doi.org/10.1177/2045893217710639 CrossRefPubMedPubMedCentral

Title: Bosentan or Macitentan Therapy in Chronic Thromboembolic Pulmonary Hypertension?
Authors: M. C. J. van Thor
L. ten Klooster
R. J. Snijder
J. C. Kelder
J. J. Mager
M. C. Post
Publication date: 01-12-2019
Publisher: Springer US
Keywords: Bosentan
Sildenafil
Pulmonary Hypertension
Pulmonary Hypertension
Pulmonary Hypertension
Pulmonary Hypertension
Riociguat
Published in: Lung / Issue 6/2019
Print ISSN: 0341-2040
Electronic ISSN: 1432-1750
DOI: https://doi.org/10.1007/s00408-019-00274-9

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