Abstract 17319: Race and Gender Differences in Response to Endothelin Receptor Antagonists among Patients with Pulmonary Arterial Hypertension
Introduction: Recent advances in pharmacotherapy for pulmonary arterial hypertension (PAH) have improved outcomes, but differences in treatment responses among subgroups of patients have not been explored. Documented race and gender differences in endothelin-1 physiology may lead to variable responsiveness to endothelin receptor antagonists (ERAs). We undertook this study to assess the hypothesis that treatment response to ERAs would vary across race and gender.
Methods: Patient-level data from all six phase III, placebo-controlled trials of ERA therapies for PAH were analyzed to estimate the change in six-minute walk distance (6MWD) from baseline to 12 weeks across race and gender. Secondary analyses used absolute distance walked at 12 weeks as the endpoint. Interactions between treatment and either race or gender were assessed using linear regression. Analyses were adjusted for treatment (ERA or placebo), baseline walk distance, diagnosis category, trial, age, race and gender. Walk distances at 12 weeks were imputed if missing. Individuals with a study-ending clinical event prior to 12 weeks were coded as having a 12-week walk distance of 0 m; this value was alternatively coded as 50 m, 100 m, 150 m, or ‘missing’ in sensitivity analyses.
Results: Among 1130 participants, the mean age was 49 years, 236 (21%) were male, 836 participants were white, and 65 were black. The placebo-adjusted response among women was 29.5 m (95% CI: 3.1 m, 55.8 m) greater than that among men (p < 0.05). The placebo-adjusted change in 6MWD among whites was 42.85 m (95% CI: −4.31, 90.01) greater than that among blacks (p=0.07). Secondary analyses using absolute distance walked and sensitivity analyses showed similar results.
Conclusions: Among patients diagnosed with PAH, response to ERAs is greater among women and possibly among whites than among men and blacks, respectively. Further research is needed to determine if these differences reflect differences in baseline risk for disease progression, biologically mediated differences in treatment response, or some other mechanism.
- © 2010 by American Heart Association, Inc.