Long-term endothelin receptor antagonism attenuates coronary plaque progression in patients with early atherosclerosis

Aim: The purpose of the current study was to determine if long term treatment with an endothelin-A (ETA) receptor antagonist attenuates the progression of coronary plaques in patients with coronary endothelial dysfunction. Methods: Thirty-five patients with non-obstructive coronary disease and coronary endothelial dysfunction were randomized in a double blind manner to treatment with placebo or ETA receptor antagonist Atrasentan (10mg) for six months. Endothelial function was assessed by the change in coronary blood flow and coronary artery diameter in response to intracoronary acetylcholine. Normalized mean total atheroma volume (TAVMEAN), percent atheroma volume (PAV) and changes of atheroma volume were assessed by intravascular ultrasound (IVUS) at baseline and 6-month follow-up. Results: In segments with coronary endothelial dysfunction, there was a significant decrease in normalized TAVMEAN and PAV at six months from baseline in the Atrasentan group compared to the placebo group median (IQR) -2.00 mm3 (-7.28, 2.53.) vs 9.11 mm3 (1.23, 14.05), p=0.0024 and 0.955% (-3.43, 1.70) vs 3.85% (-0.39, 14.59) p=0.010. There was no change in normalized TAV or PAV in the segments with normal endothelial function. Conclusion: This study demonstrates that 6-month treatmentwith Atrasentan attenuates progression of coronary plaque in segments with endothelial dysfunction.