Differential effects of simvastatin and atorvastatin on high‐density lipoprotein cholesterol and apolipoprotein A‐I are consistent across hypercholesterolemic patient subgroups

摘要

Background: In addition to lowering plasma levels of low‐density lipoprotein cholesterol (LDL‐C), statins also raise high‐density lipoprotein cholesterol (HDL‐C). Hypothesis: Recent studies have shown that treatment with simvastatin results in larger increases in HDL‐C than those seen with atorvastatin. The results of three clinical studies are analyzed, comparing the effects of simvastatin and atorvastatin on HDL‐C and apolipoprotein A‐I (apo A‐I) in the total cohort and in several subgroups of hypercholesterolemic patients. The three studies were all multicenter, randomized clinical trials that included simvastatin (20–80 mg) and atorvastatin (10–80 mg) treatment arms. The subgroup analyses performed were gender; age (<65 and ≥65 years); baseline HDL‐C (male: < 40 or ≥ 40 mg/dl; female: < 45 or ≥ 45 mg/dl), baseline LDL‐C (< 160 or ≥ 160 mg/dl), and baseline triglycerides (< 200 or ≥ 200 mg/dl). Results: Both drugs produced similar increases in HDL‐C levels at low doses; however, at higher drug doses (40 and 80 mg), HDL‐C showed a significantly greater increase with simvastatin than with atorvastatin (p< 0.05 to <0.001). Therefore, while HDL‐C remained consistently elevated across all doses of simvastatin, there appeared to be a pattern of decreasing HDL‐C with an increasing dose of atorvastatin. A similar negative dose response pattern was also observed with apo A‐I in atorvastatin‐treated patients, suggesting a reduction in the number of circulating HDL particles at higher doses. Both drugs reduced LDL‐C and triglycerides in a dose‐dependent fashion, with atorvastatin showing slightly greater effects. The differential effects of atorvastatin and simvastatin on HDL‐C and apo A‐I were observed for both the whole study cohorts and all subgroups examined; thus, no consistent treatment‐by‐subgroup interactions were observed. Conclusion: The data presented show that, across different hypercholesterolemic patient subgroups, simvastatin increases HDL‐C and apo A‐I more than atorvastatin at higher doses, with evidence of a negative dose response effect on HDL‐C and apo A‐I with atorvastatin, but not simvastatin.