Ambrisentan Benefits Class I-II Pulmonary Hypertension

SAN DIEGO — Following 2 years of treatment with ambrisentan for pulmonary arterial hypertension, patients with World Health Organization functional class I and II symptoms at baseline had a lower risk of clinical worsening and death, compared with those who had WHO class III and IV symptoms at baseline.

Patients in both subgroups also experienced improvements in 6-minute walk distance from their baseline rates.

Those are key findings from the longest-term study to date of ambrisentan (Letairis) in patients with pulmonary hypertension. The agent was approved in 2007 as a once-daily treatment for patients with WHO functional class II or III symptoms to improve exercise capacity and delay clinical worsening.

“This medication seems to work long term,” lead investigator Dr. Fernando Torres said in an interview during a poster session at an international conference of the American Thoracic Society. “Not only is it working at 2 years, but most of the patients are still on monotherapy. We did not have to add a second medication to keep them doing clinically well.”

Dr. Torres and his associates conducted a long-term extension study in 287 patients who participated in the Placebo-Controlled, Efficacy and Safety Study of Ambrisentan in Patients With Pulmonary Arterial Hypertension (ARIES)-1 and ARIES-2 trials. Patients who received ambrisentan in previous studies remained on the current dose, while patients who received placebo in previous studies were randomized to ambrisentan 5 mg or 10 mg daily.

At baseline, the mean age of the 287 patients was 50 years, and 82% of patients were female; 123 patients had WHO I and II symptoms, and 164 patients had WHO III and IV symptoms. By the second year, 20 patients with WHO I and II symptoms had discontinued the trial, as did 53 patients with WHO III and IV symptoms.

By year 2, 13% of patients with WHO I and II symptoms had no clinical worsening of disease, compared with 39% of patients with WHO III and IV symptoms, a difference that was statistically significant, reported Dr. Torres, director of the pulmonary hypertension program at the University of Texas Southwestern Medical Center, Dallas.

Patients with WHO I and II symptoms had more favorable long-term survival, compared with those who had WHO III and IV symptoms (95% vs. 83%), which was statistically significant.

The most common clinical worsening events were hospitalization for pulmonary arterial hypertension (9% in those with WHO I and II symptoms vs. 27% in those with WHO III and IV symptoms), the addition of prostanoid therapy (5% vs. 13%), and death (4% vs. 15%).

The most common adverse events resulting in death were right ventricular failure (1% in those patients with WHO I and II symptoms vs. 4% in those patients with WHO III and IV symptoms) and pulmonary hypertension (0% vs. 2%).

The majority of patients in both subgroups remained on monotherapy through year 2 (85% with WHO I and II symptoms, compared with 72% with WHO III and IV symptoms). “Most of these patients seem to be stable using just one medication,” Dr. Torres said.

He also reported that by year 2, the 6-minute walk distance was improved in both subgroups, and the change from baseline appeared to be slightly better for patients with WHO I and II symptoms at baseline.

A chief limitation of the study, Dr. Torres said, is that it lacked a placebo group, because it would be unethical to keep patients on placebo for that long.

He disclosed that he is a paid researcher, consultant, and adviser to the makers of Letairis, Gilead Sciences, which funded the study.