The Multicentre Atorvastatin Plaque Stabilisation (MAPS) Study Proposed Rationale and Study Design

Background: Inflammatory mechanisms are thought to play a key role in the development of atherosclerosis and unstable plaque. In the past, numerous studies have reported that the statins have an antiinflammatory and anti-atherosclerotic effect unrelated to lipid-lowering. However, it is still difficult to estimate the contribution of the specific cholesterol-independent effects of statins in counteracting the atherosclerotic process and its sequelae. Aim: To establish whether a short-term (3-month) treatment with atorvastatin at high versus low dose leads to changes in carotid plaque structure and biology in terms of cellular/extracellular composition, markers of inflammation, cell adhesion, and thrombosis. For comparison, the effect of another cholesterol- lowering treatment will also be evaluated. Study design: A randomised, multicentre, double-bind, parallel group study will be conducted involving 225 patients. The patients will have hypercholesterolaemia (serum total cholesterol 225–295 mg/dL) with carotid stenosis ≥70% and be planning to undergo an endarterectomy procedure. During the 3 months prior to the procedure, the patients will be randomly divided into three groups. Each group received atorvastatin 10 mg/day, atorvastatin 80 mg/day, or cholestyramine 8 g/day plus sitosterol 2.5 g/day, respectively. Expected results: The effectiveness of atorvastatin versus control medication in inducing a favourable plaque remodelling (stabilisation), a reduced level of inflammation (local and systemic), and the effectiveness of a high versus low dose of atorvastatin therapy.