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Sitaxentan

In Pulmonary Arterial Hypertension

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Abstract

  • ▴ Sitaxentan is a highly selective endothelin (ET)A receptor antagonist, with an ≈6500 higher affinity for ETA than ETB 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.

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Notes

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

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Authors and Affiliations

  1. Wolters Kluwer Health / Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland, 1311, New Zealand

    Lesley J. Scott

  2. Wolters Kluwer Health, Conshohocken, Pennsylvania, USA

    Lesley J. Scott

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Correspondence to Lesley J. Scott.

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Scott, L.J. Sitaxentan. Drugs 67, 761–770 (2007). https://doi.org/10.2165/00003495-200767050-00007

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