LAUSR

Rationale: The population of patients with pulmonary arterial hypertension (PAH) has evolved over time from predominantly young White women to an older, more racially diverse and obese population. Whether these changes are reflected in clinical trials is not known. Objectives: To determine secular and regional trends among PAH trial participants. Methods: We performed a pooled cohort analysis using harmonized data from phase III clinical trials of PAH therapies submitted to the US Food and Drug Administration. We used mixed effects linear and logistic regression to assess regional differences in participant age, sex, body habitus, and hemodynamics over time. Results: 6599 participants were enrolled in 18 trials between 1998-2013; 78% were female. The mean age of participants in North America, Europe, and Latin America at time of study start increased by 2.09 (95%CI 0.67-3.51), 1.62 (95%CI 0.24-3.00) and 4.75 (95%CI 2.29-7.21) years per 5 years, respectively (p=0.01). Body mass index at time of study start increased by 0.72 kg/m2 per 5 years (95%CI 0.44-0.99; p<0.001) across all regions. 85% of participants in early studies were non-Hispanic White, however this decreased over time to 70%. 97% of Asians and 74% of Hispanics in the sample were recruited from Asia and Latin America. Conclusions: Patients enrolled in more recent PAH therapy trials are older and more obese, mirroring the changing epidemiology of observational cohorts. However, these trends varied by geographic region. PAH cohorts remain predominantly female, presenting challenges for generalizability towards male patients. While the proportion of non-White participants increased over time, this was primarily through recruitment in Asia and Latin America.