Ambrisentan Improves Walking Distance Over the Long Term in Patients With Pulmonary Arterial Hypertension: Presented at ERS

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Title: Ambrisentan Improves Walking Distance Over the Long Term in Patients With Pulmonary Arterial Hypertension: Presented at ERS
URL: http://www.pslgroup.com/dg/22E6BE.htm
Doctor's Guide
October 9, 2008

By Chris Berrie

BERLIN -- October 9, 2008 -- Treatment with ambrisentan prevents further progression and improves functional capacity in patients with pulmonary arterial hypertension (PAH), according to phase 3 results of a long-term extension of the 12-week, double-blind Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicentre, Efficacy Study (ARIES).

On behalf of the ARIES group, Ardeschir Ghofrani, MD, Coinvestigator, Geissen University Hospital, Geissen, Germany, presented the results here on October 7 at the European Respiratory Society (ERS) 18th Annual Congress.

In the original ARIES phase 1/2 studies, ambrisentan improved 6-minute-walk distance (6MWD) in patients with PAH with of World Health Organization functional class (WHO-FC) class 2 symptoms at baseline. These studies evaluated treatment with placebo or ambrisentan 2.5, 5, or 10 mg over 12 weeks.

In the present open-label, dose-migration, extension study, researchers assessed the effects over 1 year of treatment with the same doses of ambrisentan, a high-affinity, propanoic acid-based, endothelin A receptor selective antagonist.

A comparison of the baseline characteristics of patients with WHO-FC 2 and 3 in the ARIES 1/2 study showed distinct patient populations. Patients with WHO-FC 2 had less severe disease severity, although, as Dr. Ghofrani said, "These patients are still heavily compromised by their pulmonary haemodynamics."

Results show that 6MWD improved significantly from an increase of 42.9 metres from baseline at week 12 to 61.7 metres increase at 1 year (95% confidence interval [CI], 47.5-75.9 metres).

By the end of the 1-year ambrisentan treatment extension period, patients with WHO-FC 2 (n = 104) showed low rates of clinical worsening compared with baseline (class 3, 4.8%; class 4, 1.9%), and showed higher rates of reversal of clinical worsening (class 1, 11.5%).

One-year estimates for patients with WHO-FC 2 taking ambrisentan showed a significantly greater probability of no clinical worsening (92.9%; 95% CI, 88.9%-97.0%) than the equivalent patients with WHO-FC 3 (77.9%; 95% CI, 71.5%-84.3%). Indeed, the probability of survival of these WHO-FC 2 patients treated with ambrisentan was 98.1% at 1 year and 93.2% at 2 years.

In this extended ambrisentan treatment, adverse events were reported less commonly and generally were less severe in the patients with WHO-FC 2 compared with patients with WHO-FC 3, Dr. Ghofrani said.

In the analysis of the effects on liver function, the researchers found that the incidence of aminotransferase abnormalities more than 3 times the upper limit of normal remained low during this extension study, at 2.3 events per 100 patient-years of exposure to ambrisentan.

Dr. Ghofrani concluded, "Patients with WHO-FC 2 symptoms warrant treatment with targeted therapy, with ambrisentan treatment associated with a robust improvement in 6MWD that was maintained for 1 year."

Therefore, ambrisentan represents a valuable licensed treatment option, Dr. Ghofrani said, noting, "It is worthwhile treating these patients because it not only prevents further progression, but in fact improves their functional capacity and outcome."

Funding for this study was provided by GlaxoSmithKline.

[Presentation title: Ambrisentan Therapy for PAH Patients With WHO Functional Class 2 Symptoms: One-Year Follow-Up. Abstract O3178]

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