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Original Research: Pulmonary Vascular Disease |

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

Jonathan A. Rose, MS; Jody M. Cleveland, MS; Youlan Rao, PhD; Omar A. Minai, MD; Adriano R. Tonelli, MD
Author and Funding Information

FUNDING/SUPPORT: This publication was made possible by Clinical and Translational Science Awards KL2 [Grant TR000440 to A. R. T.] from the National Center for Research Resources, a component of the National Institutes of Health (NIH), NIH Roadmap for Medical Research.

CORRESPONDENCE TO: Adriano Tonelli, MD, 9500 Euclid Ave A-90, Cleveland, OH 44195


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;149(5):1234-1244. doi:10.1016/j.chest.2015.11.008
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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.

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