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Bosentan Effective in Pulmonary Arterial Hypertension Patients Cotreated With Sildenafil: Presented at CHEST

By John Gever

CHICAGO, IL -- October 24, 2007 -- Patients with pulmonary arterial hypertension (PAH) being treated with sildenafil can have bosentan added safely to their regimen and can expect the same benefit that is achieved with bosentan alone, researchers reported here at CHEST 2007, the annual meeting of the American College of Chest Physicians.

Lewis J. Rubin, MD, Professor of Medicine and Director, Pulmonary Hypertension Program, University of California-San Diego, San Diego, California, United States, reported on a secondary analysis of data from the multicentre 185-patient Endothelin Antagonist tRial in miLdlY symptomatic PAH patients (EARLY).

The EARLY trial was a randomised, placebo-controlled, double-blind trial. It enrolled 185 patients who received 6 months of either placebo or bosentan (62.5 mg twice daily for 4 weeks, then 125 mg twice daily afterward). Included among these patients were 29 patients taking sildenafil at study entry, who were permitted to stay on the drug during the trial and were assigned in nearly equal numbers to the placebo and bosentan groups.

Results in patients cotreated with bosentan and sildenafil were largely similar to what was seen with bosentan monotherapy in the overall study sample, Dr. Rubin said in a oral presentation on October 23.

Pulmonary vascular resistance was reduced to 85% of baseline levels in the group of patients receiving both drugs (P =.0478), nearly identical to the decline seen with bosentan alone (P <.0001).

However, the data failed to show a correspondingly strong improvement in physical function, Dr. Rubin said. Among patients receiving bosentan alone and among those on bosentan and sildenafil, there was a trend toward increased 6-minute walking distance (6MWD) but it did not reach statistical significance. Most patients showed a slight to moderate improvement.

However, one patient in the sildenafil-bosentan group died during the trial, and under the study's rules, a 6MWD value of 0 was assigned to this patient at the 6-month evaluation. This skewed the results for the sildenafil-bosentan group, Dr. Rubin said, such that the mean increase from baseline in 6MWD was only 5 m compared with 15 m for patients taking bosentan alone.

"We see discordance between the haemodynamic effect and the walking effect," Dr. Rubin noted. Even if the increase in walking distance had been statistically significant, the magnitudes of the absolute numbers were probably not clinically significant, he added.

The presence of sildenafil did not affect the likelihood of clinical worsening in bosentan-treated patients, Dr. Rubin said. Bosentan significantly delayed clinical worsening relative to placebo in the overall EARLY sample (P =.014) and this advantage was preserved in those receiving sildenafil along with bosentan, he said.

Funding for this study was provided by Actelion Inc.


[Presentation title: Bosentan Improves Hemodynamics in Patients Receiving Background Sildenafil Treatment: Results from EARLY, a Randomized, Double-blind, Placebo-controlled Study in Patients with Mildly Symptomatic Pulmonary Arterial Hypertension. Abstract 900]

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