Baseline Sex Differences in Pulmonary Arterial Hypertension Randomized Clinical Trials

Area of Science:

• Cardiovascular Medicine
• Pulmonary Medicine
• Clinical Trials Research

Background:

• Pulmonary arterial hypertension (PAH) exhibits known sex-based differences, yet their specific contributions to disease metrics remain under-investigated.
• Understanding these disparities is crucial for accurate patient assessment and treatment stratification in PAH.

Purpose of the Study:

• To investigate the association between sex and baseline 6-minute walk distance (6MWD), hemodynamic parameters, and functional class in patients with PAH.
• To explore how age and body mass index (BMI) modify these sex-based relationships in PAH.

Main Methods:

• Secondary analysis of participant-level data from 18 randomized clinical trials for investigational PAH therapies (1998-2014).
• Generalized mixed modeling was used to analyze outcomes as a function of the interaction between sex and age or BMI.
• Included 6,633 participants (78% female) with PAH, primarily of idiopathic etiology.

Main Results:

• Females exhibited significantly shorter 6MWD, with a steeper decline per unit increase in BMI compared to males.
• Females presented with lower right atrial pressure (RAP) and mean pulmonary artery pressure, alongside a higher cardiac index than males.
• Age modified the sex-specific relationships for RAP and mean pulmonary artery pressure, while BMI influenced pulmonary vascular resistance (PVR) differently between sexes.

Conclusions:

• Significant sexual dimorphism exists in PAH clinical trial participants, affecting 6MWD and hemodynamic profiles.
• The interplay of age and BMI critically influences these sex-based differences, underscoring their importance in PAH assessment.
• Incorporating sex, age, and body size considerations is vital for the accurate evaluation and interpretation of surrogate outcomes in PAH research and clinical practice.