Race and sex differences in response to endothelin receptor antagonists for pulmonary arterial hypertension

Chest. 2012 Jan;141(1):20-26. doi: 10.1378/chest.11-0404. Epub 2011 Sep 22.


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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antihypertensive Agents / therapeutic use*
  • Bosentan
  • Child
  • Double-Blind Method
  • Endothelin Receptor Antagonists*
  • Ethnicity*
  • Exercise Test
  • Familial Primary Pulmonary Hypertension
  • Female
  • Follow-Up Studies
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / ethnology
  • Hypertension, Pulmonary / physiopathology
  • Isoxazoles / therapeutic use
  • Male
  • Middle Aged
  • Phenylpropionates / therapeutic use
  • Prevalence
  • Prospective Studies
  • Pulmonary Wedge Pressure / drug effects
  • Pyridazines / therapeutic use
  • Sex Factors
  • Sulfonamides / therapeutic use
  • Thiophenes / therapeutic use
  • Treatment Outcome
  • United States / epidemiology
  • Walking / physiology
  • Young Adult


  • Antihypertensive Agents
  • Endothelin Receptor Antagonists
  • Isoxazoles
  • Phenylpropionates
  • Pyridazines
  • Sulfonamides
  • Thiophenes
  • ambrisentan
  • sitaxsentan
  • Bosentan