Effects of the Acyl Coenzyme A:Cholesterol Acyltransferase Inhibitor Avasimibe on Human Atherosclerotic Lesions

Abstract

Background-Inhibition of the acyl coenzyme A:cholesterol acyltransferase (ACAT) enzyme may prevent excess accumulation of cholesteryl esters in macrophages. The ACAT inhibitor avasimibe was shown to reduce experimental atherosclerosis. This study was designed to investigate the effects of avasimibe on human coronary atherosclerosis. Methods and Results-This randomized, double-blind, placebo-controlled trial assessed the effects of avasimibe at dosages of 50, 250, and 750 mg QD on the progression of coronary atherosclerosis as assessed by intravascular ultrasound (IVUS). All patients received background lipid-lowering therapy if necessary to reach a target baseline LDL level Ͻ125 mg/dL (3.2 mmol/L). IVUS and coronary angiography were performed at baseline and repeated after up to 24 months of treatment. Approximately equal percentages of patients across groups received concurrent statin therapy (87% to 89%). The mean total plaque volume at baseline was Ϸ200 mm 3 , and the least squares mean change at end of treatment was 0.7 mm 3 for placebo and 7.7, 4.1, and 4.8 mm 3 for the avasimibe 50, 250, and 750 mg groups, respectively (adjusted Pϭ0.17 [unadjusted Pϭ0.057], 0.37, and 0.37, respectively). Percent atheroma volume increased by 0.4% with placebo and by 0.7%, 0.8%, and 1.0% in the respective avasimibe groups (PϭNS). LDL cholesterol increased during the study by 1.7% with placebo but by 7.8%, 9.1%, and 10.9% in the respective avasimibe groups (PϽ0.05 in all groups). Conclusions-Avasimibe did not favorably alter coronary atherosclerosis as assessed by IVUS. This ACAT inhibitor also caused a mild increase in

Glycaemic status influences the nature and severity of coronary artery disease

“…In 25 centres in Canada, US, Europe, Australia and South Africa, 525 patients had a baseline IVUS assessment [13,14]. Of these, 426 also had an evaluable repeat IVUS examination with glycaemic data [14]. These patients underwent clinically indicated coronary angiography at baseline for suspected or proven CAD.…”

“…Patients undergoing percutaneous coronary intervention of a non-IVUS target artery could be included. The protocol was approved by the Institutional Review Boards of all participating sites [14] and all patients gave written informed consent.…”

Evaluation of coronary atheroma by 64-slice multidetector computed tomography: Comparison with intravascular ultrasound and angiography

“…La sensibilité et la spécificité de la TDMC utilisée pour dépister les sténoses de plus de 50 % observées à la CGQ sont excellentes avec une administration préalable de nitroglycérine. required (8). Also, nitroglycerin was not systematically administered before MDCT in many previous comparative studies, which sometimes involved its use before invasive angiography only (9).…”

“…The methods of the IVUS procedure were detailed previously (8). Briefly, single-vessel IVUS studies were performed using 40 MHz IVUS catheters (Boston Scientific, USA).…”

Prevention challenges: The era of atherosclerosis regression

“…Several studies (2)(3)(4)(5)(6) have demonstrated that statins have allowed us to enter the era of atherosclerosis regression. Indeed, 12 months of treatment with simvastatin has been shown to result in a reduced coronary atheroma volume, as assessed by intravascular ultrasound (2).…”