A new drug to reduce plaque progression in early atherosclerosis

The authors aimed to evaluate the use of Atresantan, an Endothelin-1 receptor (ET_A) inhibitor, in early atherosclerosis.

Endothelial dysfunction is when the thin layer of cells on the inside of blood vessels produce fewer proteins that cause the vessel to dilate or widen and more proteins that lead to inflammation. It is an early stage of atherosclerosis (deposition of fatty material on the inner walls of the arteries).

Endothelin-1 is a protein that causes constriction or narrowing of the blood vessels and plays an important role in the development of endothelial dysfunction and progression of atherosclerosis through its receptor, ET_A. The aim of the present study was to test the hypothesis that long-term treatment with Atresantan, a drug that inhibits activation of the ET_A receptor, would reduce the progression of coronary plaques (fatty deposits) in patients with early atherosclerosis and endothelial dysfunction.

35 patients were included in the study. Patients were randomly assigned to either 10 mg oral Atrasentan daily or placebo for 6 months in addition to standard medical therapy.

In artery segments with endothelial dysfunction, average atheroma volume (the size of the accumulated fatty material or atherosclerotic plaque in the artery wall) increased by 9 mm³ in the placebo group compared to a decrease of 2 mm³ in the Atrasentan group. The percent atheroma volume (proportion of the total vessel volume occupied by the atherosclerotic plaque) increased by 3.85% in the placebo group compared to 0.955% in the Atrasentan group. After adjusting for characteristics at the beginning of the study and medication use (including treatment with statins), Atrasentan was associated with a significant reduction of both total atheroma volume and percentage atheroma volume compared to placebo.

There were no differences observed in artery segments where endothelial dysfunction was not present.

The authors declared that this study demonstrated that 6 month treatment with Atrasentan reduces plaque progression in coronary artery segments with endothelial dysfunction.

It is not known if this drug will be applicable to patients with significant atherosclerosis or unstable coronary artery disease.