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To compare the effects of concentrated n-3 fatty acids (Omacor™) and gemfibrozil in patients with severe hypertriglyceridaemia. The primary objective was to measure the change in serum triglyceride (TG), and the secondary objectives were to study the changes in total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), very low density lipoprotein cholesterol (VLDL-C), apolipoproteins and free fatty acids. 89 patients with severe hypertriglyceridaemia (defined as plasma TG >4.5 mmol/L) were randomised to receive in a double-blind fashion either Omacor™, a capsule containing the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at a dosage of 4 g/day, or gemfibrozil 1200 mg/day for 12 weeks. The baseline characteristics of the two randomised groups were similar. Compared with baseline, n-3 fatty acids and gemfibrozil reduced mean TG levels by 28.9 and 51.2%, respectively (p = 0.007). TC was decreased 10.2% with n-3 fatty acids, and 13.0% with gemfibrozil (p = 0.51), and VLDL-C was reduced 11.8 and 19.4% (p = 0.49) with n-3 fatty acids and gemfibrozil, respectively. HDL-C was increased by both compounds; n-3 fatty acids elevated HDL-C by only 1.2%, whereas it was elevated 27.9% by gemfibrozil (p = 0.012). Our study indicated that both n-3 fatty acids and gemfibrozil markedly decreased TG levels in patients with severe hypertriglyceridaemia. Gemfibrozil, however, decreased TG levels and increased HDL-C significantly more than n-3 fatty acids.

Objectives: This single-blind, multicentre study in a large cohort of hypercholesterolaemic patients with or without coronary heart disease (CHD) was designed to evaluate the additional low density lipoprotein cholesterol (LDL-C)— lowering effect of atorvastatin over milligram-equivalent doses of simvastatin. Methods: 378 patients treated with either simvastatin 20 or 40mg, with baseline LDL-C values >2.6 mmol/L, were randomised to four groups: patients on 20mg simvastatin were randomised to either simvastatin 20mg (n = 129) or atorvastatin 20mg (n = 124), and patients on 40mg simvastatin were randomised to simvastatin 40mg (n = 64) or atorvastatin 40mg (n = 61). The investigator was blinded for study medication during the 8-week treatment phase, the patient was not. Lipid profiles were measured at screening, randomisation and at study completion. The primary efficacy parameter was the relative change in LDL-C level within and between groups. Statistical significance was assessed with analysis of variance. Results: No major differences in baseline patient characteristics were found with regard to demographic variables, vital signs, cardiovascular risk factors, concomitant medication or lipid profiles. The mean (±SD) relative decreases of LDL-C from baseline were: 14.0 ± 14.1% for atorvastatin 20mg (n = 107) versus 3.3 ± 14.1% for simvastatin 20mg (n = 108) [p = 0.0001], and 14.7 ± 15.2% for atorvastatin 40mg (n = 55) versus 2.9 ± 12.7% for simvastatin 40mg (n = 54) [p = 0.0001]. The relative change of LDL-C from baseline in the overall atorvastatin group (n = 162) versus the overall simvastatin group (n = 162) was 14.2 ± 14.4% versus 3.2 ± 13.6% (p = 0.0001). This involved an additional decrease of 11% in the atorvastatin versus the simvastatin group. The percentage of high risk patients according to the European Atherosclerosis Society/National Cholesterol Education Program (EAS/NCEP) who initially did not meet these goals but reached them at week 8, was 48/34% (for atorvastatin 20mg) versus 20/14% (for simvastatin 20mg) [p = 0.005 and p = 0.007, respectively], and 58/18% (for atorvastatin 40mg) versus 24/10% (for simvastatin 40mg) [p = 0.005 and not significant, respectively]. Conclusion: Our results indicated that patients with hypercholesterolaemia on simvastatin 20 or 40mg who are switched to a milligram-equivalent dose of atorvastatin, will reach significantly lower LDL-C values within 8 weeks of treatment, with a greater percentage of high risk patients reaching their EAS or NCEP targets.

Objective: Hypercholesterolaemia is strongly associated with increased vessel wall thickness as measured by ultrasound. The question is whether aggressive cholesterol lowering with high-dose atorvastatin can alter intima media thickening to a greater extent than conventional therapy in patients with familial hypercholesterolaemia (FH). The baseline characteristics of a double-blind, randomised trial are described to determine whether two active treatments (high-dose atorvastatin 80mg versus conventional dose simvastatin 40mg), administered over a period of 2 years, may retard the process of intima 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 discontinued. Thereafter, baseline measurements of lipoprotein parameters and intima 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 difference was found for the internal carotid artery (ICA). In the carotid bifurcation, IMT was 1.20 ± 0.50mm in men and 1.1 ± 0.54mm in women. The IMT of the common femoral artery (CFA) was 2.03 ± 0.88mm in men with cardiovascular disease (CVD) and 1.63 ± 0.70mm in men without CVD (p < 0.05). Strikingly, plaques were present in all men and 95% of the women with CVD. The cholesterol-year score and HDL cholesterol levels partially explained the variation in IMT in the carotid bifurcation, whereas gender and smoking contributed 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-documented FH population exhibiting marked increases in IMT of both carotid and femoral arteries and a very high prevalence of plaques, indicating extreme CVD risk. Since lipid-lowering therapy provides the highest benefit in precisely such patients, the ASAP trial will help assess whether aggressive LDL cholesterol intervention leads to retardation of subclinical atherosclerosis progression, as estimated with ultrasonographically assessed IMT.