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Meta-analysis of comparative efficacy of increasing dose of Atorvastatin versus Rosuvastatin versus Simvastatin on lowering levels of atherogenic lipids (from VOYAGER).

The American journal of cardiology (2010-01-28)
Stephen J Nicholls, Gunnar Brandrup-Wognsen, Mike Palmer, Philip J Barter
ABSTRACT

Statins are the most commonly prescribed agents for lowering levels of low-density lipoprotein (LDL) cholesterol. Although dose-dependent reductions in levels of atherogenic lipids are observed with all statins, the impact of increasing dose has not been fully elucidated. An individual patient data pooled analysis was performed of 32,258 patients in studies comparing the efficacy of rosuvastatin with that of atorvastatin or simvastatin. The impact of increasing dose on lowering LDL cholesterol, triglycerides, non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein B was investigated. Doubling the dose of each statin was accompanied by a 4% to 7% greater degree of lowering of all atherogenic lipids. A stronger correlation was observed between changes in LDL cholesterol and non-HDL cholesterol (r = 0.92, p <0.001) or apolipoprotein B (r = 0.76, p <0.001) than triglycerides (r = 0.14, p <0.001). On multivariate analysis, baseline lipid level (p <0.0001) and increasing statin dose (p <0.0001) were strong predictors of achieving treatment goals in high-risk patients. Increasing age was a strong independent predictor of achieving goal for all atherogenic lipids (p <0.0001). Achieving LDL cholesterol goals was also more likely in women (p <0.0001), patients with diabetes (p <0.0001), and patients without atherosclerotic disease (p = 0.0002). In contrast, normal triglyceride levels were more often observed in men (p <0.0001) and patients without diabetes mellitus (p = 0.03). In conclusion, doubling statin dose was associated with greater lowering of LDL cholesterol by 4% to 6% and non-HDL cholesterol by 3% to 6%. Greater lipid goal achievement with increasing dose supports the use of high-dose statin therapy for more effective cardiovascular prevention.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Simvastatin, ≥97% (HPLC), solid
Supelco
Simvastatin, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Simvastatin, analytical standard
USP
Simvastatin, United States Pharmacopeia (USP) Reference Standard
Simvastatin, European Pharmacopoeia (EP) Reference Standard