NEW YORK (Reuters Health) – Long-term ambrisentan therapy safely improves exercise capacity in patients with pulmonary arterial hypertension (PAH), according to results of an extension protocol that followed two earlier randomized trials.

The 12-week ARIES-1 and -2 trials, reported in 2005, led to regulatory approval for the 5- and 10-mg doses of ambrisentan for PAH, Dr. Ronald J. Oudiz, from Harbor-UCLA Medical Center, Torrance, California, and colleagues note in the Journal of the American College of Cardiology for November 17.

Patients who participated in either of those two studies were eligible for the ARIES-E extension study. Subjects in the treatment arms continued on their current regimens, and subjects in placebo groups were randomized to 2.5, 5 or 10 mg once daily.

Of 383 patients who were randomized in the original trials, 261 had follow-up data at 2 years.

Treatment with ambrisentan at 5- and 10-mg doses was associated with 23-and 28-meter increases in 6-min walk distance relative to baseline. The 2.5-mg dose, by contrast, did not provide a sustained benefit at 2 years.

When the groups were combined, overall survival rates at 1 and 2 years were 94% and 88%, respectively. Rates of freedom from clinical worsening at 1 and 2 years were 83% and 72%, respectively.

The most common side effects with ambrisentan were peripheral edema, headache, upper respiratory tract infection, and dizziness. Most effects were mild and did not lead to drug discontinuation. The annualized risk of aminotransferase abnormalities greater than three-times the upper limit of normal was roughly 2% per year.

“The long-term use of ambrisentan over a 2-year period resulted in sustained improvements in exercise capacity and dyspnea, a stabilization of WHO functional class, a low risk of clinical worsening and death, and an acceptable safety profile that was similar to that seen in the 12-week placebo-controlled trials,” the authors conclude. “These data support the use of ambrisentan as part of a long-term strategy for the treatment of patients with PAH.”

Reference:
J Am Coll Cardiol 2009;54:1971-1981.