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Original Research: PULMONARY VASCULAR DISEASE |

Race and Sex Differences in Response to Endothelin Receptor Antagonists for Pulmonary Arterial HypertensionRace and Sex and Endothelin Receptor Antagonists

Nicole B. Gabler, PhD, MHA; Benjamin French, PhD; Brian L. Strom, MD, MPH; Ziyue Liu, PhD; Harold I. Palevsky, MD, FCCP; Darren B. Taichman, MD, PhD, FCCP; Steven M. Kawut, MD, FCCP; Scott D. Halpern, MD, PhD
Author and Funding Information

From the Center for Clinical Epidemiology and Biostatistics and the Department of Biostatistics and Epidemiology (Drs Gabler, French, Strom, Kawut, and Halpern); the Pulmonary, Allergy, and Critical Care Division (Drs Palevsky, Taichman, Kawut, and Halpern); Penn Cardiovascular Institute (Drs French, Palevsky, Taichman, Kawut, and Halpern), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; and the Department of Biostatistics (Dr Liu), Indiana University-Purdue University Indianapolis, Indianapolis, IN.

Correspondence to: Scott D. Halpern, MD, PhD, Perelman School of Medicine, University of Pennsylvania, 723 Blockley Hall, 423 Guardian Dr, Philadelphia, PA 19104-6021; e-mail: shalpern@exchange.upenn.edu


For editorial comment see page 4

Funding/Support: This work was supported by an American Thoracic Society Fellows Career Development Award and an Actelion Pharmaceuticals Entelligence Young Investigator Award (Dr Halpern).

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2012 American College of Chest Physicians


Chest. 2012;141(1):20-26. doi:10.1378/chest.11-0404
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Background:  Recently studied therapies for pulmonary arterial hypertension (PAH) have improved outcomes among populations of patients, but little is known about which patients are most likely to respond to specific treatments. Differences in endothelin-1 biology between sexes and between whites and blacks may lead to differences in patients’ responses to treatment with endothelin receptor antagonists (ERAs).

Methods:  We conducted pooled analyses of deidentified, patient-level data from six randomized placebo-controlled trials of ERAs submitted to the US Food and Drug Administration to elucidate heterogeneity in treatment response. We estimated the interaction between treatment assignment (ERA vs placebo) and sex and between treatment and white or black race in terms of the change in 6-min walk distance from baseline to 12 weeks.

Results:  Trials included 1,130 participants with a mean age of 49 years; 21% were men, 74% were white, and 6% were black. The placebo-adjusted response to ERAs was 29.7 m (95% CI, 3.7-55.7 m) greater in women than in men (P = .03). The placebo-adjusted response was 42.2 m for whites and −1.4 m for blacks, a difference of 43.6 m (95% CI, −3.5-90.7 m) (P = .07). Similar results were found in sensitivity analyses and in secondary analyses using the outcome of absolute distance walked.

Conclusions:  Women with PAH obtain greater responses to ERAs than do men, and whites may experience a greater treatment benefit than do blacks. This heterogeneity in treatment-response may reflect pathophysiologic differences between sexes and races or distinct disease phenotypes.


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