Effects of maximal doses of atorvastatin versus rosuvastatin on small dense low-density lipoprotein cholesterol levels

Authors: MASUMI, AI - Tufts University; OTOKOZAWA, SEIKO - Tufts University; ASZTALOS, BELA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; NAKAJIMA, KATSUYUKI - Tufts University; STEIN, EVAN - Metabolic & Atherosclerosis Research Center; JONES, PETER - Baylor College Of Medicine; SCHAEFER, ERNST - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: American Journal of Cardiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/27/2007
Publication Date: 2/1/2008
Citation: Masumi, A., Otokozawa, S.M., Asztalos, B.F., Nakajima, K., Jones, P., Schaefer, E. 2008. Effects of maximal doses of atorvastatin versus rosuvastatin on small dense low-density lipoprotein cholesterol levels. American Journal of Cardiology. 10:315-318.

Interpretive Summary: The major cholesterol carrying particles in the bloodstream are known as low density lipoproteins or LDL. High levels of LDL cholesterol (> 160 mg/dl) have been associated with an increased risk of heart disease, a leading cause of death and disability in our society. Another cholesterol carrying particle in the bloodstream is known as high density lipoprotein cholesterol. Low levels of high density lipoprotein (HDL) cholesterol (< 40 mg/dl in men and < 50 mg/dl in women) have also been associated with an increased risk of coronary heart disease. LDL is known to deposit cholesterol in tissues, while HDL is known to remove it for return to the liver and excretion from the body. There are two kinds of LDL in the bloodstream, large LDL, and small dense LDL. Of these small dense LDL is more likely to enter the artery wall and promote cholesterol deposits and clogging of the artery. Diets low in animal fat and cholesterol and enriched in plant food and vegetable oil have been shown to lower LDL cholesterol and reduce the risk of heart disease. In addition medications have been developed that decrease cholesterol production in the body and also lower LDL cholesterol and reduce the risk of developing heart disease. These medicines are called statins. The most effective statins in terms of LDL cholesterol lowering are atorvastatin and rosuvastatin. We tested the effects of maximal doses of these agents on total LDL cholesterol and small dense LDL cholesterol, using new direct assays for these parameters. In 271 middle aged and elderly people with elevated cholesterol levels studied over 6 weeks, atorvastatin (80 mg/day) and rosuvastatin (40 mg/day) lowered triglycerides 26% and 24%, LDL cholesterol 50% and 52%, and small dense LDL cholesterol 46% and 53%. Therefore maximal doses of both these agents were highly effective in lowering LDL cholesterol and small dense LDL cholesterol, with rosuvastatin being somewhat more effective than atorvastatin. It has clearly been shown that lowering elevated blood cholesterol (> 240 mg/dl) and elevated low density lipoprotein (LDL) cholesterol (> 160 mg/dl) with diet and statin medications can reduce the risk of heart disease. This study shows that statins not only are effective in lowering total LDL cholesterol, but also small dense LDL cholesterol, the LDL particle most likely to enter the artery and cause heart disease. Moreover these agents can lower these parameters by more than 50%. The information indicates that certainly all patients with heart disease as well as those at high risk (those with diabetes or more than 20% ten year risk of developing heart disease) should be on effective diet and statin treatment for heart disease prevention.

Technical Abstract: Maximal doses of atorvastatin and rosuvastatin are highly effective in lowering low-density lipoprotein (LDL) cholesterol and triglyceride levels; however, rosuvastatin has been shown to be significantly more effective than atorvastatin in lowering LDL cholesterol and in increasing high-density lipoprotein (HDL) and its subclasses. Our purpose in this post hoc subanalysis of an open-label study was to compare the effects of daily oral doses of rosuvastatin 40 mg with atorvastatin 80 mg over a 6-week period on direct LDL cholesterol and small dense LDL (sdLDL) cholesterol in 271 hyperlipidemic men and women versus baseline values. Rosuvastatin was significantly (p <0.01) more effective than atorvastatin in decreasing sdLDL cholesterol (53% vs 46%), direct LDL cholesterol (52% vs50%), total cholesterol/HDL cholesterol ratio (46% vs 39%), and non-HDL cholesterol (51% vs 48%), The magnitude of these differences was modest, and the 2 statins caused similar decreases in triglyceride levels (24% and 26%). In conclusion, our data indicate that the 2 statins, given at their maximal doses, significantly and beneficially alter the entire spectrum of lipoprotein particles, but that rosuvastatin is significantly more effective than atorvastatin in lowering direct LDL cholesterol and sdLDL cholesterol.