Rationale, design and baseline characteristics of a clinical trial comparing the effects of robust vs conventional cholesterol lowering and intima media thickness in patients with familial hypercholesterolaemia - The Atorvastatin versus Simvastatin on Atherosclerosis Progression (ASAP) study

Objective: Hypercholesterolaemia is strongly associated with increased vess el wall thickness as measured by ultrasound. The question is whether aggres sive cholesterol lowering with high-dose atorvastatin can alter intima medi a thickening to a greater extent than conventional therapy in patients with familial hypercholesterolaemia (FH). The baseline characteristics of a dou ble-blind, randomised trial are described to determine whether two active t reatments thigh-dose atorvastatin 80mg versus conventional dose simvastatin 40mg), administered over a period of 2 years, may retard the process of in tima media thickening in the carotid and femoral arteries of patients with FH. Design and Patients: 325 patients with FH were randomised. Patients entered an 8-week placebo period in which all lipid-lowering medication was discon tinued. Thereafter, baseline measurements of lipoprotein parameters and int ima media thickness (IMT) of carotid and femoral artery were performed. Results: Baseline low density lipoprotein (LDL) cholesterol (+/-SD) levels were 8.11 +/- 1.92 mmol/L (312 +/- 73 mg/dl) in men and 8.22 +/- 1.91 mmol/ L (316 +/- 73 mg/dl) in women, respectively. Mean posterior wall IMT in the left common carotid artery (CCA) was significantly greater in men (0.94 +/ - 0.29mm) compared with women (0.85 +/- 0.20) [p < 0.05]. A similar differe nce was found for the internal carotid artery (ICA). In the carotid bifurca tion, IMT was 1.20 +/- 0.50mm in men and 1.1 +/- 0.54mm in women. The IMT o f the common femoral artery (CFA) was 2.03 +/- 0.88mm in men with cardiovas cular disease (CVD) and 1.63 +/- 0.70mm in men without CVD (p < 0.05). Stri kingly, plaques were present in all men and 95% of the women with CVD. The cholesterol-year score and HDL cholesterol levels partially explained the v ariation in IMT in the carotid bifurcation, whereas gender and smoking cont ributed to the variation in IMT in the CFA in this group of patients. Conclusion: The patients participating in the Atorvastatin and Simvastatin on Atherosclerosis Progression (ASAP) trial constitute the largest well-doc umented FH population exhibiting marked increases in IMT of both carotid an d femoral arteries and a very high prevalence of plaques, indicating extrem e CVD risk. Since lipid-lowering therapy provides the highest benefit in pr ecisely such patients, the ASAP trial will help assess whether aggressive L DL cholesterol intervention leads to retardation of subclinical atheroscler osis progression, as estimated with ultrasonographically assessed IMT.