Effect of Age on Phenotype and Outcomes in Pulmonary Arterial Hypertension Trials

Abstract

Background: In recent years, the population of patients with pulmonary arterial hypertension (PAH) has changed dramatically, including more advanced age at diagnosis. We hypothesized that older patients have a distinct clinical profile with different disease characteristics and response to intervention.

Methods: All previously published treatment studies for PAH conducted by United Therapeutics including seven randomized, placebo-controlled trials and one extension study were included and analyzed to assess the association of age with various demographic, functional, hemodynamic, and outcome variables.

Results: A total of 2,627 patients across three age groups were included: ≤ 50 (n = 1,438, 54.7%), 51 to 64 (n = 780, 29.7%), and ≥ 65 years (n = 409, 15.6%). In comparison with the youngest group, the oldest age group had higher proportions of connective tissue disease-associated etiology (range across the studies, 27%-49% vs 13%-21%), higher proportions of New York Heart Association Functional classes III and IV (74%-91% vs 57%-84%), shorter baseline 6-min walk distance (6MWD) (261-316 vs 335-371 m), better hemodynamic measurements including lower baseline mean pulmonary artery pressure (48-51 vs 58-63 mmHg), and smaller changes in 6MWD from baseline to endpoint (-5.6 to 24 vs 14-43 m). Age remained associated with change in 6MWD when adjusting for covariates in multivariate analyses.

Conclusions: For the first time, using data from large randomized controlled trials, this study characterizes the different phenotype and outcomes of older patients with PAH, which includes different disease etiology, diminished functional status, and decreased response to intervention. This may have significant implications for the management of this patient population and design of future therapy trials.

Keywords: age; outcomes; pulmonary arterial hypertension; pulmonary hypertension.

Figure 1

Etiologies of PAH and baseline 6MWD (mean ± SE) for each age group. For each of the three age groups, the percentage of patients with CTD-PAH and IPAH is shown. 6MWD = 6-min walk distance; CTD-PAH = connective tissue disease-pulmonary arterial hypertension; FREEDOM = Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease; IPAH = idiopathic pulmonary arterial hypertension; PAH = pulmonary arterial hypertension; PHIRST = Pulmonary Arterial Hypertension and Response to Tadalafil; SC-TRE+TRUST = Subcutaneous Infusion of Treprostinil in Patients with PAH + Study of Intravenous Remodulin in Patients in India with PAH; TRIUMPH = Treprostinil Sodium Inhalation Used in the Management of Pulmonary Arterial Hypertension.

Figure 2

Baseline hemodynamics (mean ± SE) for each age group. See Figure 1 legend for expansion of abbreviations.

Figure 3

Change in 6MWD (mean ± SE) for each age group. See Figure 1 legend for expansion of abbreviations.