Abstract 19723: Randomized Comparison of Bosentan in Intermittent Claudication in Peripheral Arterial Disease : The Clinical and Endotelial Function Assessment after Endothelin Receptor Antagonism (CLAU) Randomized Controlled Trial

Abstract

INTRODUCTION There is evidence that endothelin-1 (ET-1) is involved in the etiopathology of Peripheral Arterial Disease (PAD) due to its capacity to induce impairment of the endothelial function, its vasoconstrictor effects, its pro-inflammatory cytokine action, fibrosis and induction of cell proliferation. Bosentan is a dual ET-1 receptor antagonist, administered orally with antifibrotic, antiinflamatory, antihipertrophic properties and the capacity to vasodilate selectively the damaged vascular bed. MATERIAL AND METHODS A prospective, randomized, controlled, parallel groups, simple blind, proof-of-concept trial was performed in 30 male patients (50-60 years old) with Intermittent Claudication (Rutherford category 1-2) recently diagnosed, and clinical manifestations not exceeding 6 months, with hypertension and/or dyslipidemia as unique cardiovascular risk factors burden permitted. After a 2-weeks period of stabilization of the claudication distance verified in two consecutive treadmill test (12.5%,3.2 km/h), patients were randomized 1:1 to the experimental arm (Bosentan 62.5 mg twice daily/four weeks and 125mg twice daily/eight weeks) or control group. RESULTS After six months of treatment there was an increase in the Absolute Claudication Distance (ADC) of 549% (p=0.003), the Flow-Mediated Artery Dilation (FMAD) of 768% (p=0.001), the Ankle-Brachial Index (ABI) 24% (p<0.001) and a decrease in the C Reactive Protein (CRP) of -22,7%(p<0.019) vs. control group (22%,-16%,-8%,21%, respectively). The patient subjective claudication assessment corroborated the improvement in the ability to walk (589%, p <0.001) in the treatment group. No severe adverse events were reported in the experimental group. CONCLUSIONS Bosentan improves significantly the Claudication Distance, the endothelial function, inflammatory and the hemodynamic status in patients with incipient PAD.