Gender Differences in Response to PAH Therapy: 6MWD and Time to Clinical Worsening

Purpose Pulmonary Arterial Hypertension is a female predominant disease but there is little data on therapy response by gender. 1 We assessed treatment response in males vs females by examining change in six-minute walk distance (6MWD) and time to clinical worsening (TCW). We also investigated the effects of menopause on treatment response using age as a predictor of menopausal status. 1. Shapiro S, et al. REVEAL. Chest. 2011;10-3114. Methods and Materials 6MWD was recorded before and after 16 weeks of treatment in the PHIRST study in a cohort of 340 subjects (264 F and 76 M), among a total of 405 subjects (317 F and 88 M). 2 Wilcoxon Rank sum test was used to assess gender effect on change in 6MWD and Log-rank test was used to assess gender effect on TCW. The females were subdivided by age to estimate menopausal status: 14-44 yrs premenopausal, 45-55yrs perimenopausal and ≥56yrs postmenopausal. Log-rank test was performed on TCW by age among females. 2.Galie N, et al. Tadalafil Therapy for PH. Circulation. 2009;10.1161. Results A statistically significant difference in change in 6MWD among males vs females (Median: 51.5 m vs. 26.5 m; p=0.008) was found. Log-rank test, however, did not show a consistent gender effect on TCW. There was a trend for a female age-dependent effect in change in 6MWD; the premenopausal group showed the greatest improvement, followed by peri- and postmenopausal. However, Log-rank test did not show a consistent age group effect on TCW. Conclusions Overall these analyses indicate a need for further investigation of the effects of gender and menopause on treatment response. Despite significant differences between the genders in 6MWD there was no consistent gender effect on TCW. It is possible that a smaller change in 6MWD may be tolerated in females. Given the suggested trend for more progressive worsening in postmenopausal females, a longitudinal study may be helpful to characterize this trend. Future work might explore the correlation between 6MWD and TCW in women.