OBJECTIVES: Pulmonary arterial hypertension (PAH) is progressive and fatal. Hemodynamic parameters, physical functioning (PF), and health-related quality of life (HRQoL) worsen without treatment. The objective was to evaluate the distribution of changes in exercise capacity, hemodynamic parameters, and HRQoL in PAH patients treated with sitaxentan. Because cumulative distribution functions (CDFs) characterize treatment effects beyond conventional statistical significance (which is achievable in large studies with small changes that lack clinical meaning), this method was employed. METHODS: Adult PAH patients (n=178) received 12 weeks of randomized, double-blind treatment with placebo (n=60) or sitaxentan 100 (n=55) or 300 (n=63) mg once daily. The primary outcome measure was change in percent of predicted peak VO2 (PVO2); 6-minute walk distance (6MWD) measured exercise capacity. Hemodynamic assessments included pulmonary and systemic vascular resistance (PVR and SVR, respectively), pulmonary capillary wedge pressure (PCWP), and cardiac index (CI). The Short Form-36 (SF-36) assessed HRQoL, including the PF domain. CDFs plotted the cumulative percentage of patients against percentage (and, separately, numeric) changes from baseline to week 12 in outcome measures. Kolmogorov-Smirnov tests assessed differences in separation between CDFs for sitaxentan and placebo. RESULTS: Significant differences between CDFs were observed for sitaxentan 300 mg (but not 100 mg) vs placebo for both numeric and percentage change in percent of predicted PVO2 (P=0.03). Significant differences occurred for sitaxsentan 100 and 300 mg vs placebo for 6MWD, PVR, SVR, and CI (P<0.02 for each); the PCWP difference was significant only for percentage change at the 100-mg sitaxentan dose. No differences occurred for the SF-36 PF domain.   CONCLUSIONS: Using CDF analysis incorporating the entire distribution of responses, sitaxentan significantly improved percent of predicted PVO2 (by numeric and percentage changes,  300-mg dose), 6MWD, PVR, SVR, CI, and PCWP (by percentage change, 100-mg dose), but not the SF-36 PF domain in PAH patients .