An initial combination treatment with Tracleer (bosentan) and Ventavis (iloprost, inhalation solution) dramatically improved exercise capacity and clinical function in patients with pulmonary arterial hypertension (PAH), compared to treatment with either of those medications alone.
The study, “Treatment of pulmonary arterial hypertension using initial combination therapy of bosentan and iloprost,” was published in the journal Respiratory Care.
Starting treatment with a single drug is a very common PAH strategy. Combination therapies, where a second or third drug is added to the first, are used if the patient does not respond to the treatment or the condition worsens. But little research exists as to an “initial” combination therapy, where the patient receives two drugs at the beginning of a treatment — and is particularly sparse concerning patients with more severe symptoms (WHO class III or IV PAH).
Researchers in China compared the effectiveness of an initial combination of oral bosentan and inhaled iloprost, and single-therapy with either of those drugs, in relation to exercise capacity, function, and quality of life.
Twenty-seven untreated PAH patients with WHO functional class III or IV were distributed into a combination therapy group receiving bosentan (125 mg x 2 times/day) and iloprost (10 μg 4-6 times/day), or two groups given one of these two drugs.
Changes in exercise capacity were measured using the 6-minutes walk distance test (6MWD) before start of treatment and again after six weeks and three months of treatment. Clinical symptoms and heart- and circulatory capacity were also evaluated.
Results showed an improved exercise capacity in patients treated with Tracleer and Ventavis at six weeks and three months post-treatment, compared to both single-treatment groups. A significant, mean increase of 133.8 meters in 6MWD after three months was recorded in combination patients, compared to 0.9 meters in the Tracleer group, and 10.2 meters in the Ventavis group.
In the combination group after three months of treatment, 62.5% of the patients were classified as WHO functional class I, and the remaining 37.5 % as class II.
In addition, pulmonary artery pressure, cardiac index, and quality of life improved after three months. Combination patients also showed decreased levels of N-terminal pro b-type natriuretic peptide, a marker for heart activity (increased levels indicate heart failure).
A previous study, REVEAL (NCT00370214), looking at PAH disease management, found that patients with WHO functional class III and IV were not sufficiently treated, and that starting a single treatment and then an add-on second medication was inadequate. Later, the AMBITION study (NCT01178073 ), the “first to compare the use of upfront combination therapy,” ambrisentan and tadalafil, showed the combination improved treatment results in untreated PAH patients, compared to single therapy with either drug.
In this study, researchers applied the AMBITION trial model, using a combination of Tracleer and Ventavis. They concluded that “[i]nitial combination therapy in untreated PAH patients with WHO functional class III or IV can significantly improve 6MWD, hemodynamics, and quality of life compared with monotherapy.”