Clinical trial NCT01053065: The Multicenter Atorvastatin Plaque Stabilization (MAPS) Study
Official title: The Multicenter Atorvastatin Plaque Stabilization (MAPS) Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Symptomatic Carotid Stenosis
Hypercholesterolemia
Indication for Carotid Endarterectomy
Keywords: Atherosclerosis
Macrophages
Carotid arteries
Statin
Lead sponsor: University of Padova
Sponsor class: OTHER
Collaborators: name: Biomedical Foundation for Cardiovascular Research of Padova
name: Pfizer
First posted: 2010-01-21
Enrollment: 60
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The impact on cardiovascular events achieved by statin therapy seems to be mostly attributable to the cholesterol-lowering effect with a highly debated contribution of the lipid-independent pleiotropic effects. However, a short-term benefit has been documented for patients treated with statins in acute coronary syndromes and other clinical settings. These observations strengthened the hypothesis of additional, so-called pleiotropic actions of statins.

The investigators therefore sought to investigate how different lipid-lowering strategies (non-statin therapy, low-dose statin and high-dose statin) affects cellular composition of carotid plaque over a short-term period of three months. Specifically the investigators tried and dissect the LDL-C lowering impact on plaque cellular composition as compared to the lipid-independent contribution on plaque macrophage and smooth muscle cells.

Detailed description: Patients (with Total Cholesterol (TC) ranging between 5.83-7.64 mmol/l), never treated with lipid lowering drugs, with symptomatic carotid stenosis \>70% (NASCET criteria), and therefore eligible for carotid endarterectomy, were recruited. All patients were enrolled within 30 days from the clinical event, and randomized to one of three treatment groups. Each group, composed of 20 patients, received atorvastatin 10 mg/day (AT-10 group), or atorvastatin 80 mg/day (AT-80 group), or cholestyramine (Questran, Bristol Myer Squibb) 8 g/day plus sitosterol (Unilever) 2.5 g/day (C-S group) for three months prior to the vascular procedure. A placebo group was not included for ethical reasons due to the high cardiovascular risk profile in this population.

Eligibility criteria: Inclusion Criteria:

* Symptomatic carotid stenosis \> 70% (NASCET criteria)
* Eligibility for carotid endarterectomy
* Total cholesterol level between 5.83 and 7.64 mmol/L
* Never treated with lipid lowering drugs

Exclusion Criteria:

* Previous lipid lowering therapy
* Total cholesterol \<5.83 or \>7.64 mmol/L
* Evidence of chronic inflammatory disease (clinical and laboratory).
* Patients at high risk for cerebrovascular events (i.e. ulcerated carotid plaque, recurrent TIAs).

Primary outcomes:
measure: Changes in cellular composition of carotid plaque.
timeFrame: Three months
Secondary outcomes:
Other outcomes:
Locations:
city: Chieti
country: Italy
facility: University of Chieti Medical School
city: Padova
country: Italy
facility: University of Padova Medical School
city: Treviso
country: Italy
facility: University of Padova Medical School - Treviso Branch
Study officials:
affiliation: University of Padova - Italy
name: Paolo Pauletto, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pauletto P, Puato M, Faggin E, Santipolo N, Pagliara V, Zoleo M, Deriu GP, Grego F, Plebani M, Sartore S, Bon GB, Heymes C, Samuel JL, Pessina AC. Specific cellular features of atheroma associated with development of neointima after carotid endarterectomy: the carotid atherosclerosis and restenosis study. Circulation. 2000 Aug 15;102(7):771-8. doi: 10.1161/01.cir.102.7.771.
citation: Faggin E, Zambon A, Puato M, Deeb SS, Bertocco S, Sartore S, Crepaldi G, Pessina AC, Pauletto P. Association between the --514 C-->T polymorphism of the hepatic lipase gene promoter and unstable carotid plaque in patients with severe carotid artery stenosis. J Am Coll Cardiol. 2002 Sep 18;40(6):1059-66. doi: 10.1016/s0735-1097(02)02116-2.