Chest
Volume 145, Issue 4, April 2014, Pages 810-817
Journal home page for Chest

Original Research: Pulmonary Vascular Disease
Bosentan for Sarcoidosis-Associated Pulmonary Hypertension: A Double-Blind Placebo Controlled Randomized Trial

https://doi.org/10.1378/chest.13-1766Get rights and content

Background

Sarcoidosis-associated pulmonary hypertension (SAPH) is a common problem in patients with persistent dyspneic sarcoidosis. The objective of this study was to determine the effect of bosentan therapy on pulmonary arterial hemodynamics in patients with SAPH.

Methods

This 16-week study was a double-blind, placebo-controlled trial of either bosentan or placebo in patients with SAPH confirmed by right-sided heart catheterization. Patients were enrolled from multiple academic centers specializing in sarcoidosis care. They were stable on sarcoidosis therapy and were receiving no therapy for pulmonary hypertension. The cohort was randomized two to one to receive bosentan at a maximal dose of 125 mg or placebo bid for 16 weeks. Pulmonary function studies, 6-min walk test, and right-sided heart hemodynamics, including pulmonary artery mean pressure and pulmonary vascular resistance (PVR), were performed before and after 16 weeks of therapy.

Results

Thirty-five patients completed 16 weeks of therapy (23 treated with bosentan, 12 with placebo). For those treated with bosentan, repeat hemodynamic studies at 16 weeks demonstrated a significant mean ± SD fall in PA mean pressure (−4 ± 6.6 mm Hg, P = .0105) and PVR (−1.7 ± 2.75 Wood units, P = .0104). For the patients treated with placebo, there was no significant change in either PA mean pressure (1 ± 3.7 mm Hg, P > .05) or PVR (0.1 ± 1.42 Wood units, P > .05). There was no significant change in 6-min walk distance for either group. Two patients treated with bosentan required an increase of supplemental oxygen by > 2 L after 16 weeks of therapy.

Conclusions

This study demonstrated that bosentan significantly improved pulmonary hemodynamics in patients with SAPH.

Trial registry

ClinicalTrials.gov; No: NCT00581607; URL: www.clinicaltrials.gov

Section snippets

Materials and Methods

Patients aged 18 to 90 years with sarcoidosis defined by standard criteria16 were eligible for consideration. The patients were included if they had documented pulmonary hypertension with a PA mean pressure ≥ 25 mm Hg as measured by cardiac catheterization within 6 months of entry into the study. Pulmonary artery occlusion pressure (PAOP), left ventricular end-diastolic pressure, or both was < 15 mm Hg. Patients had to exhibit New York Heart Association (NYHA) functional class II or III

Results

Forty-three patients from five sites were enrolled in the study over a 4-year period, ending in September 2011. Figure 1 summarizes the outcomes for these patients. Four patients were never randomized because of withdrawn consent (two patients) or ineligibility (one each for liver dysfunction and NYHA functional class IV). Of the 39 randomized patients, 35 completed 16 weeks of therapy. Five patients declined repeat right-sided heart catheterization but continued in the study. One patient had a

Discussion

Based on case reports and series,12, 15, 21 we studied the effectiveness of bosentan in the treatment of SAPH. We found that 16 weeks of bosentan treatment was associated with a significant improvement in pulmonary hemodynamics as measured by both PA mean pressure and PVR. No improvement in pulmonary hemodynamics was found in the placebo group. The change in PA mean pressure was significantly different between the groups, and no significant changes in functional class, quality of life, or 6MWD

Acknowledgments

Author contributions: Dr Baughman had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Dr Baughman: contributed to the study design and execution, patient recruitment, and review of the final manuscript.

Dr Culver: contributed to the study design and execution, patient recruitment, and review of the final manuscript.

Dr Cordova: contributed to the study design and execution, patient recruitment, and review of

References (36)

  • E Panselinas et al.

    Acute pulmonary exacerbations of sarcoidosis

    Chest

    (2012)
  • V Faoro et al.

    Bosentan decreases pulmonary vascular resistance and improves exercise capacity in acute hypoxia

    Chest

    (2009)
  • N Galiè et al.

    Guidelines on diagnosis and treatment of pulmonary arterial hypertension

    Eur Heart J

    (2004)
  • VV McLaughlin et al.

    ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: developed in collaboration with the American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association

    Circulation

    (2009)
  • VV McLaughlin et al.

    Survival with first-line bosentan in patients with primary pulmonary hypertension

    Eur Respir J

    (2005)
  • JM Bourbonnais et al.

    Clinical predictors of pulmonary hypertension in sarcoidosis

    Eur Respir J

    (2008)
  • RP Baughman et al.

    Inhaled iloprost for sarcoidosis associated pulmonary hypertension

    Sarcoidosis Vasc Diffuse Lung Dis

    (2009)
  • MA Judson et al.

    Ambrisentan for sarcoidosis associated pulmonary hypertension

    Sarcoidosis Vasc Diffuse Lung Dis

    (2011)
  • Cited by (122)

    • Sarcoidosis-Associated Pulmonary Hypertension

      2024, Clinics in Chest Medicine
    • Update on cardiac sarcoidosis

      2023, Trends in Cardiovascular Medicine
    • Pulmonary Hypertension in Interstitial Lung Disease

      2022, Archivos de Bronconeumologia
    View all citing articles on Scopus

    Funding/Support: This study was supported by Actelion Pharmaceuticals US, Inc.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

    View full text