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Improvement of vascular endothelial function using the oral endothelin receptor antagonist bosentan in patients with systemic sclerosis.
Arthritis Rheum. 2007 Jun; 56(6):1985-93.AR

Abstract

OBJECTIVE

Increased endothelin activity may play a role in the pathogenesis of vascular injury, a primary feature of systemic sclerosis (SSc; scleroderma). Our goal was to test the hypothesis that treatment with the oral endothelin receptor antagonist bosentan might improve vascular endothelial function in SSc patients.

METHODS

A 4-week, prospective, parallel-group study compared 12 SSc patients who did not receive bosentan treatment with 12 patients who did receive treatment (125 mg/day) for pulmonary hypertension and/or digital ulcers. There were no differences in demographic and clinical characteristics or medications between the 2 groups. Baseline endothelial dysfunction was documented by decreased brachial artery ultrasound-derived flow-mediated dilation (FMD%; <5.5). Pulse wave analysis, venous occlusion plethysmography, and measurement of serum vascular markers were performed in parallel.

RESULTS

FMD%, the main end point, increased significantly from a mean +/- SD of 3.1 +/- 1.3% to 8.4 +/- 2.6% after 4 weeks of bosentan treatment (P < 0.001, compared with a change from 2.4 +/- 1.6% to 2.4 +/- 2.2% in control patients). Arterial blood pressure, endothelium-independent vascular function, augmentation index, peripheral flow reserve, as well as circulating intercellular adhesion molecule 1, E-selectin, vascular endothelial growth factor, and endothelin 1 were not significantly affected by bosentan treatment. In patients continuously treated for 4 months, during which the dosage of bosentan remained at 125 mg/day (n = 5) or increased to 250 mg/day (n = 5), the 4-week results remained unchanged.

CONCLUSION

Small doses of bosentan improve endothelial function without affecting hemodynamic parameters or endothelial activation-related processes, thus supporting a direct, reversible effect of endothelin in SSc-associated vascular injury. A long-term, controlled trial to examine the potentially global clinical benefit of endothelin receptor blockade in patients with early SSc may be warranted.

Authors+Show Affiliations

First Department of Propedeutic and Internal Medicine, Laikon Hospital, Athens University Medical School, Athens, Greece. psfikakis@med.uoa.grNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17530638

Citation

Sfikakis, P P., et al. "Improvement of Vascular Endothelial Function Using the Oral Endothelin Receptor Antagonist Bosentan in Patients With Systemic Sclerosis." Arthritis and Rheumatism, vol. 56, no. 6, 2007, pp. 1985-93.
Sfikakis PP, Papamichael C, Stamatelopoulos KS, et al. Improvement of vascular endothelial function using the oral endothelin receptor antagonist bosentan in patients with systemic sclerosis. Arthritis Rheum. 2007;56(6):1985-93.
Sfikakis, P. P., Papamichael, C., Stamatelopoulos, K. S., Tousoulis, D., Fragiadaki, K. G., Katsichti, P., Stefanadis, C., & Mavrikakis, M. (2007). Improvement of vascular endothelial function using the oral endothelin receptor antagonist bosentan in patients with systemic sclerosis. Arthritis and Rheumatism, 56(6), 1985-93.
Sfikakis PP, et al. Improvement of Vascular Endothelial Function Using the Oral Endothelin Receptor Antagonist Bosentan in Patients With Systemic Sclerosis. Arthritis Rheum. 2007;56(6):1985-93. PubMed PMID: 17530638.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Improvement of vascular endothelial function using the oral endothelin receptor antagonist bosentan in patients with systemic sclerosis. AU - Sfikakis,P P, AU - Papamichael,C, AU - Stamatelopoulos,K S, AU - Tousoulis,D, AU - Fragiadaki,K G, AU - Katsichti,P, AU - Stefanadis,C, AU - Mavrikakis,M, PY - 2007/5/29/pubmed PY - 2007/7/21/medline PY - 2007/5/29/entrez SP - 1985 EP - 93 JF - Arthritis and rheumatism JO - Arthritis Rheum. VL - 56 IS - 6 N2 - OBJECTIVE: Increased endothelin activity may play a role in the pathogenesis of vascular injury, a primary feature of systemic sclerosis (SSc; scleroderma). Our goal was to test the hypothesis that treatment with the oral endothelin receptor antagonist bosentan might improve vascular endothelial function in SSc patients. METHODS: A 4-week, prospective, parallel-group study compared 12 SSc patients who did not receive bosentan treatment with 12 patients who did receive treatment (125 mg/day) for pulmonary hypertension and/or digital ulcers. There were no differences in demographic and clinical characteristics or medications between the 2 groups. Baseline endothelial dysfunction was documented by decreased brachial artery ultrasound-derived flow-mediated dilation (FMD%; <5.5). Pulse wave analysis, venous occlusion plethysmography, and measurement of serum vascular markers were performed in parallel. RESULTS: FMD%, the main end point, increased significantly from a mean +/- SD of 3.1 +/- 1.3% to 8.4 +/- 2.6% after 4 weeks of bosentan treatment (P < 0.001, compared with a change from 2.4 +/- 1.6% to 2.4 +/- 2.2% in control patients). Arterial blood pressure, endothelium-independent vascular function, augmentation index, peripheral flow reserve, as well as circulating intercellular adhesion molecule 1, E-selectin, vascular endothelial growth factor, and endothelin 1 were not significantly affected by bosentan treatment. In patients continuously treated for 4 months, during which the dosage of bosentan remained at 125 mg/day (n = 5) or increased to 250 mg/day (n = 5), the 4-week results remained unchanged. CONCLUSION: Small doses of bosentan improve endothelial function without affecting hemodynamic parameters or endothelial activation-related processes, thus supporting a direct, reversible effect of endothelin in SSc-associated vascular injury. A long-term, controlled trial to examine the potentially global clinical benefit of endothelin receptor blockade in patients with early SSc may be warranted. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/17530638/Improvement_of_vascular_endothelial_function_using_the_oral_endothelin_receptor_antagonist_bosentan_in_patients_with_systemic_sclerosis_ L2 - https://doi.org/10.1002/art.22634 DB - PRIME DP - Unbound Medicine ER -