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First-line ambrisentan plus tadalafil halved PAH events
Key clinical point: First-line combination therapy with ambrisentan plus tadalafil cut the rate of clinical events in pulmonary arterial...
The Food and Drug Administration has approved the combined use of ambrisentan (Letairis) and tadalafil for the treatment of pulmonary arterial hypertension based on positive results from the AMBITION trial, according to Gilead Sciences.
In the trial, 605 PAH patients with World Health Organization functional class II or III symptoms were randomly assigned to receive either ambrisentan, tadalafil, or a combination of the two. One-month outcomes were significantly better in the combination group, with only 8% of patients needing to be hospitalized for worsening PAH, compared with 22% in the ambrisentan group and 15% in the tadalafil group (N Engl J Med. 2015 Aug 27. doi: 10.1056/NEJMoa1413687).
Improvement from baseline in 6-minute walk distance after 24 weeks was also higher in the combination group, where patients walked a median of 24 meters farther than did the ambrisentan group and 20 meters more than did the tadalafil group.
Side effects tended to be more common in the combination group than in either of the single-drug groups, with the most common side effect, peripheral edema, affecting 45% of the combination group, 38% of the ambrisentan group, and 28% of the tadalafil group. Other common side effects included headache, nasal congestion, cough, anemia, dyspepsia, and bronchitis.
“Patients receiving ambrisentan and tadalafil up front are less likely to experience disease progression or be hospitalized, and have more improvement in exercise ability than patients receiving either effective therapy alone. As such, this combination represents a new treatment strategy for patients living with this debilitating and life-threatening disease,” Dr. Ronald J. Ortiz, professor of medicine at the University of California, Los Angeles, and an AMBITION investigator, said in a statement.
Ambrisentan, an endothelin receptor antagonist, was approved in 2007 as monotherapy for PAH to improve exercise ability and delay clinical worsening. Tadalafil, a phosphodiesterase type 5 inhibitor, was approved in 2009 to improve exercise ability in PAH patients.
Find the full press release on the Gilead website.