Bosentan, a dual endothelin-receptor antagonist, was evaluated in a randomized, placebo-controlled trial for patients with pulmonary arterial hypertension (PAH). The study enrolled 213 patients with PAH, either primary or associated with connective-tissue disease, who were randomized to receive placebo or bosentan at 62.5 mg twice daily for 4 weeks, followed by 125 or 250 mg twice daily for 12 weeks. The primary endpoint was the change in six-minute walking distance (6MWD), with secondary endpoints including the Borg dyspnea index, World Health Organization (WHO) functional class, and time to clinical worsening. At week 16, patients treated with bosentan showed a significant improvement in 6MWD, with a mean difference of 44 m compared to the placebo group (95% CI, 21 to 67; P<0.001). Bosentan also improved the Borg dyspnea index, WHO functional class, and delayed clinical worsening. The 125 mg dose was well tolerated, with no significant increase in adverse events compared to placebo. The 250 mg dose showed greater improvement in 6MWD but had a higher incidence of liver enzyme elevations. Subgroup analyses showed consistent benefits across different patient groups, including those with primary PAH and those with PAH associated with scleroderma. The 250 mg dose had a more pronounced effect on improving 6MWD and reducing dyspnea, but the dose-response relationship was not clear. The study confirmed the efficacy of bosentan in improving exercise capacity and delaying clinical worsening in PAH patients. Safety was generally good, with the most common adverse events being abnormal hepatic function, which was more frequent in the 250 mg group. Bosentan did not significantly affect heart rate or mean arterial pressure. Three patients died during the study, with two in the placebo group and one in the bosentan group. The study found that bosentan significantly increased the time to clinical worsening and reduced the proportion of patients in WHO functional class IV. The results support the use of bosentan as an effective and well-tolerated treatment for PAH, particularly at the 125 mg dose. The study highlights the potential of endothelin-receptor antagonism in managing PAH, with bosentan showing significant clinical benefits. However, long-term effects and survival outcomes were not evaluated in this trial.Bosentan, a dual endothelin-receptor antagonist, was evaluated in a randomized, placebo-controlled trial for patients with pulmonary arterial hypertension (PAH). The study enrolled 213 patients with PAH, either primary or associated with connective-tissue disease, who were randomized to receive placebo or bosentan at 62.5 mg twice daily for 4 weeks, followed by 125 or 250 mg twice daily for 12 weeks. The primary endpoint was the change in six-minute walking distance (6MWD), with secondary endpoints including the Borg dyspnea index, World Health Organization (WHO) functional class, and time to clinical worsening. At week 16, patients treated with bosentan showed a significant improvement in 6MWD, with a mean difference of 44 m compared to the placebo group (95% CI, 21 to 67; P<0.001). Bosentan also improved the Borg dyspnea index, WHO functional class, and delayed clinical worsening. The 125 mg dose was well tolerated, with no significant increase in adverse events compared to placebo. The 250 mg dose showed greater improvement in 6MWD but had a higher incidence of liver enzyme elevations. Subgroup analyses showed consistent benefits across different patient groups, including those with primary PAH and those with PAH associated with scleroderma. The 250 mg dose had a more pronounced effect on improving 6MWD and reducing dyspnea, but the dose-response relationship was not clear. The study confirmed the efficacy of bosentan in improving exercise capacity and delaying clinical worsening in PAH patients. Safety was generally good, with the most common adverse events being abnormal hepatic function, which was more frequent in the 250 mg group. Bosentan did not significantly affect heart rate or mean arterial pressure. Three patients died during the study, with two in the placebo group and one in the bosentan group. The study found that bosentan significantly increased the time to clinical worsening and reduced the proportion of patients in WHO functional class IV. The results support the use of bosentan as an effective and well-tolerated treatment for PAH, particularly at the 125 mg dose. The study highlights the potential of endothelin-receptor antagonism in managing PAH, with bosentan showing significant clinical benefits. However, long-term effects and survival outcomes were not evaluated in this trial.