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01-04-2007 | Adis Drug Profile

Sitaxentan

In Pulmonary Arterial Hypertension

Author: Lesley J. Scott

Published in: Drugs | Issue 5/2007

Abstract

▴ Sitaxentan is a highly selective endothelin (ET)_A receptor antagonist, with an ≈6500 higher affinity for ET_A than ET_B receptors. In pulmonary arterial hypertension (PAH), elevated ET-1 levels are strongly correlated with disease severity and prognosis.
▴ Sitaxentan 100mg once daily was efficacious in the management of moderate to severe PAH in the pivotal, 12–18 week, large (n ≥ 98), well designed, placebo-controlled STRIDE-1, -2 and -4 trials.
▴ In the STRIDE-1 and -2 trials (the majority of patients had New York Heart Association [NYHA]/WHO functional class III PAH), sitaxentan-treated patients experienced significantly greater improvements from baseline in distance walked over 6 minutes (6MWD; primary endpoint in STRIDE-2) and in NYHA/WHO functional class than placebo recipients.
▴ In STRIDE-4, although there was no between-group difference in terms of improvements in 6MWD in the primary analysis of patients across all WHO functional classes (61% were functional class II) [primary endpoint], improvements in 6MWD significantly favoured sitaxentan versus placebo-treated patients in a post hoc subgroup analysis of those with WHO functional class III or IV disease.
▴ The beneficial effects of sitaxentan therapy on exercise capacity and NYHA/WHO functional class were maintained after up to 2 years’ treatment.
▴ Treatment with sitaxentan for up to 2 years was generally well tolerated in clinical trials.

The use of trade names is for product identification purposes only and does not imply endorsement.

D’Alonzo GE, Barst RJ, Ayres SM, et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med 1991; 115 (5): 343–9PubMed

Liu C, Liu K, Ji Z, et al. Treatments for pulmonary arterial hypertension. Respir Med 2006; 100 (5): 765–74PubMedCrossRef

Farber HW, Loscalzo J. Mechanisms of disease: pulmonary arterial hypertension. N Engl J Med 2004; 351 (16): 1655–65PubMedCrossRef

Galiè N, Manes A, Branzi A. Evaluation of pulmonary arterial hypertension. Curr Opin Cardiol 2004; 19 (6): 575–81PubMedCrossRef

O’Callaghan DS, Gaine SP. Sitaxsentan: an endothelin-A receptor antagonist for the treatment of pulmonary arterial hypertension. Int J Clin Pract 2006; 60 (4): 475–81PubMedCrossRef

Hoeper MM. Drug treatment of pulmonary arterial hypertension: current and future agents. Drugs 2005; 65 (10): 1337–54PubMedCrossRef

Galie N, Manes A, Branzi A. The endothelin system in pulmonary arterial hypertension. Cardiovasc Res 2004; 61 (2): 227–37PubMedCrossRef

European Medicines Agency. Annex I: summary of product characteristics (Thelin™) [online]. Available from URL: http://www.emea.europa.eu/ [Accessed 2006 Nov 26]

Wu C, Chan MF, Stavros F, et al. Discovery of TBC11251, a potent, long acting, orally active endothelin receptor-A selective antagonist. J Med Chem 1997; 40 (11): 1690–7PubMedCrossRef

10.

European Medicines Agency. Scientific discussion (Thelin™) [online]. Available from URL: http://www.emea.europa.eu/ [Accessed 2006 Nov 26]

11.

Rubinstein I. Prolonged anti-hypertensive effects of oral sitaxsentan, a selective ET(A) endothelin receptor antagonist, in spontaneously hypertensive hamsters. Cardiovasc Drugs Ther 2006; 20: 387–90PubMedCrossRef

12.

Givertz MM, Colucci WS, LeJemtel TH, et al. Acute endothelin A receptor blockade causes selective pulmonary vasodilation in patients with chronic heart failure. Circulation 2000; 101: 2922–7PubMedCrossRef

13.

Ooi H, Colucci WS, Givertz MM. Endothelin mediates increased pulmonary vascular tone in patients with heart failure: demonstration by direct intrapulmonary infusion of sitaxsentan. Circulation 2002; 106 (13): 1618–21PubMedCrossRef

14.

Coyne C, Kramer W. No clinical interaction between sitaxsentan and sildenafil [abstract no. P3623]. Eur Respir J 2005; 26 Suppl. 49: 563. Plus poster presented at the 15th European Respiratory Society Annual Congress; 2005 Sep 17–21; Copenhagen

15.

Barst RJ, Langleben D, Frost A, et al. Sitaxsentan therapy for pulmonary arterial hypertension. Am J Respir Crit Care Med 2004 Feb 15; 169 (4): 441–7PubMedCrossRef

16.

Langleben D, Brock T, Dixon R, et al. STRIDE 1: effects of the selective ET(A) receptor antagonist, sitaxsentan sodium, in a patient population with pulmonary arterial hypertension that meets traditional inclusion criteria of previous pulmonary arterial hypertension trials. J Cardiovasc Pharmacol 2004; 44 Suppl. 1: 80–4CrossRef

17.

Girgis R, McLaughlin V, Hill N, et al. Sitaxsentan improves 6MW and hemodynamics in patients with pulmonary arterial hypertension (PAH) related to connective tissue disease (CTD) [abstract no. FR10086 plus poster]. 2005 Annual European Congress of Rheumatology; 2005 Jun 8–11; Vienna

18.

McLaughlin V, Barst R. Sitaxsentan improves 6MW and hemodynamics in patients with pulmonary arterial hypertension related to connective tissue disease [abstract no. P3626]. Eur Respir J Suppl 2005; 26 Suppl. 49: 564. Plus poster presented at the 15th European Respiratory Society Meeting; 2005 Sep 17–21; Copenhagen

19.

Barst RJ, Langleben D, Badesch D, et al. Treatment of pulmonary arterial hypertension with the selective endothelin-A receptor antagonist sitaxsentan. J Am Coll Cardiol 2006 May 16; 47 (10): 2049–56PubMedCrossRef

20.

Pulido T, Kurzyna M, Souza R, et al. Sitaxsentan 100 mg proves more effective than sitaxsentan 50 mg in patients with pulmonary arterial hypertension [abstract]. Proceedings of the American Thoracic Society 2006; 3 Abstr. Suppl.: A417

21.

Barst RJ, Rich S, Widlitz A, et al. Clinical efficacy of sitaxsentan, an endothelin-A receptor antagonist, in patients with pulmonary arterial hypertension: open-label pilot study. Chest 2002 Jun; 121 (6): 1860–8PubMedCrossRef

22.

Benza RL, Mehta S, Keogh A, et al. Sitaxsentan treatment for patients with pulmonary arterial hypertension discontinuing bosentan. J Heart Lung Transplant 2007; 26 (1): 63–9PubMedCrossRef

23.

Ivy DD, Coyne TC, Frost A. Sitaxsentan for pulmonary arterial hypertension patients with clinical deterioration or significantly abnormal liver function test on bosentan [abstract no. P597]. Eur Heart J 2005 Sep; 26 Abstr. Suppl.: 79–80. Plus poster presented at the European Society of Cardiology Congress; 2005 Sep 3–7; Stockholm

24.

Frost A, Ivy D. Sitaxsentan for pulmonary arterial hypertension patients with clinical deterioration or significantly abnormal liver function test on bosentan [abstract]. Proceedings of the American Thoracic Society 2005; 2 Abstr. Suppl.: 204. Plus poster presented at the American Thoracic Society 2005 International Conference; 2005 May 20–25; San Diego, (CA)

25.

Langleben D, Hirsch AM, Shalit E, et al. Sustained symptomatic, functional, and hemodynamic benefit with the selective endothelin-A receptor antagonist, sitaxsentan, in patients with pulmonary arterial hypertension: a 1-year follow-up study. Chest 2004 Oct; 126 (4): 1377–81PubMedCrossRef

26.

Langleben D, Hirsch AM, Shalit E, et al. Sustained efficacy with the selective endothelin-a receptor antagonist, sitaxsentan, after two years of therapy in patients with pulmonary arterial hypertension [abstract no. P1334]. Europ Respir J Suppl. 2005 Sep; 26 Suppl. 49: 204s–5s. Plus oral presentation at the 15th European Respiratory Society Annual Congress; 2005 Sep 17–21, Copenhagen

27.

Langleben D, Hirsch AM, Shalit E, et al. Sustained efficacy with the highly selective orally-active endothelin-A receptor antagonist, sitaxsentan, after two years of therapy in patients with pulmonary arterial hypertension [abstract no. THU0115]. Plus poster presented at the 2005 Annual European Congress of Rheumatology; 2005 June 8–11; Vienna

28.

Benza R, Frost A, Girgis R, et al. Chronic treatment of pulmonary arterial hypertension (PAH) with sitaxsentan and bosentan [abstract]. Proceedings of the 102nd International Conference of the American Thoracic Society; 2006 May 19–24; San Diego, (CA), A729

29.

Oudiz RJ, Frost AE, Lawrence EC, et al. Sitaxsentan improves time to clinical worsening (TCW) in patients with pulmonary arterial hypertension (PAH) [abstract no. 92]. J Heart Lung Transplant 2006; 25 (2 Suppl. 1): S75CrossRef

30.

Benza RL, Keogh AM, Ivy DD, et al. Sitaxsentan improves six minute walk distance in patients with pulmonary arterial hypertension related to congenital heart defects [abstract no. 94]. J Heart Lung Transplant 2006; 25 (2 Suppl. 1): S76CrossRef

31.

Souza R, Martins BC, Jardim C, et al. Effect of sitaxsentan treatment on quality of life in pulmonary arterial hypertension. Int J Clin Pract 2007; 61 (1): 153–6PubMedCrossRef

32.

Barst RJ. Sitaxsentan: a selective endothelin-A receptor antagonist, for the treatment of pulmonary arterial hypertension. Expert Opin Pharmacother 2007; 8 (1): 95–109PubMedCrossRef

33.

Girgis RE, Keogh AM, Benza RL, et al. Incidence of abnormal liver function tests in patients with pulmonary arterial hypertension treated for one year with sitaxsentan or bosentan [abstract no. 55]. J Heart Lung Transplant 2006; 25 (2 Suppl. 1): 62–3CrossRef

34.

Garces PC, Alford KL, Henry NS, et al. Do liver function abnormalities with bosentan recur with sitaxsentan [abstract no. FRI0068]. Ann Rheum Dis 2005; 64 Suppl. III: 278. Plus poster presented at 2005 Annual European Congress of Rheumatology; 2005 Jun 8–11; Vienna

Title: Sitaxentan
In Pulmonary Arterial Hypertension
Author: Lesley J. Scott
Publication date: 01-04-2007
Publisher: Springer International Publishing
Published in: Drugs / Issue 5/2007
Print ISSN: 0012-6667
Electronic ISSN: 1179-1950
DOI: https://doi.org/10.2165/00003495-200767050-00007

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Sitaxentan

In Pulmonary Arterial Hypertension

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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