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Ambrisentan

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Abstract

  • ▴ Elevated endothelin (ET)-1 levels are strongly correlated with the pathogenesis and prognosis of pulmonary arterial hypertension (PAH). Ambrisentan is an orally active, highly selective ETa receptor antagonist with >4000-fold higher selectivity over the ETb receptor.

  • ▴ In two large, well designed, 12-week, placebo-controlled, phase III trials (ARIES-1, n = 202 and ARIES-2, n = 192) in patients with PAH (WHO group I), ambrisentan 2.5–10 mg once daily significantly increased 6-minute walk distance by 31–59 m from baseline (primary outcome measure) versus placebo.

  • ▴ The incidence of clinical worsening (secondary outcome measure) was significantly delayed for the combined ambrisentan 5 mg once daily groups versus the combined placebo groups from ARIES-1 and -2.

  • ▴ At week 12, WHO functional class distribution was significantly improved with once-daily ambrisentan 5 mg, and Borg dyspnoea scores were significantly improved with ambrisentan 2.5–10 mg versus placebo in combined data from the ARIES-1 and -2 trials.

  • ▴ The beneficial effects of ambrisentan on exercise capacity, WHO functional class and Borg dyspnoea scores seen at 12 weeks were maintained at 48 weeks in the ARIES-E phase III extension trial (n = 361). One-year survival rates with ambrisentan were 95–97%.

  • ▴ Treatment with ambrisentan for up to 2.8 years was generally well tolerated in clinical trials.

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Notes

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

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Acknowledgements and Disclosures

This manuscript was reviewed by: N. Galiè, Institute of Cardiology, University of Bologna, Bologna, Italy; A. Manes, Institute of Cardiology, University of Bologna, Bologna, Italy.

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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Correspondence to Jamie D. Croxtall.

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Croxtall, J.D., Keam, S.J. Ambrisentan. Drugs 68, 2195–2204 (2008). https://doi.org/10.2165/00003495-200868150-00008

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