Endothelin (ET) is involved in the etiopathogenesis of peripheral arterial disease
(PAD). We hypothesized that ET antagonism might improve the endothelial function,
inflammatory status, and symptoms in PAD. This pilot randomized clinical trial was
designed to determine the clinical efficacy, pleiotropic effects, and safety of dual
ET-receptor antagonist bosentan in Hispanic patients with PAD presenting intermittent
claudication. The Bosentan Population-Based Randomized Trial for Clinical and Endothelial
Function Assessment on Endothelin Antagonism Therapy was a 12-month, randomized, controlled,
parallel-group, double-blind, proof-of-concept pilot study evaluating the effect of
bosentan on absolute claudication distance (primary efficacy end point), flow-mediated
arterial dilation, and C-reactive protein levels (primary pleiotropic end points)
in patients with PAD with Rutherford category 1 to 2 of recent diagnosis. Secondary
end points included ankle-brachial index, subjective claudication distance, and safety.
Of the 629 screened subjects, 56 patients were randomized 1:1 to receive bosentan
for 12 weeks (n = 27) or placebo (n = 29). Six months after the initiation, a significant
treatment effect in flow-mediated arterial dilation of 2.43 ± 0.3% (95% CI 1.75 to
3.12; p = 0.001), absolute claudication distance of 283 ± 23 m (95% CI 202 to 366;
p = 0.01), ankle-brachial index of 0.16 ± 0.03 (95% CI 0.09 to 0.23; p = 0.001), and
a decrease in C-reactive protein levels of −2.0 ± 0.5 mg/L (95% CI −2.8 to −1.1; p =
0.02) were observed in the bosentan-treated group compared to the control group. No
severe adverse effects were found in the bosentan group. In conclusion, in Hispanic
patients with intermittent claudication, bosentan was well tolerated and improved
endothelial function and claudication distance as well as inflammatory and hemodynamic
states.
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Article Info
Publication History
Published online: November 05, 2015
Accepted:
October 14,
2015
Received in revised form:
October 14,
2015
Received:
July 11,
2015
Footnotes
This clinical trial was funded by a Research Grant from the Foundation of the Spanish Society for Angiology and Vascular Surgery (Madrid, Spain).
Clinical Trial Registration: Clinical Trial registered at clinicaltrials.gov, registration number: NCT25102012, (http://clinicaltrials.gov/ct2/show/NCT01738542).
See page 300 for disclosure information.
Identification
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