Rosuvastatin for the Treatment of Hypercholesterolemia

Nicole S. Culhane, Pharm.D.; Shana L. Lettieri, Pharm.D.; Jeannine R. Skae, Pharm.D.


Pharmacotherapy. 2005;25(7):990-1000. 

In This Article

Abstract and Introduction

Rosuvastatin, a new hydrophilic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin), is approved as an adjunct to diet in patients with primary hypercholesterolemia, mixed dyslipidemia, or Fredrickson type IV hypercholesterolemia. Because of its increased affinity for the reductase, rosuvastatin reduces the low-density lipoprotein cholesterol (LDL) level more than atorvastatin, simvastatin, and pravastatin do, without additional adverse effects. In addition, cytochrome P450 isoenzymes do not extensively metabolize rosuvastatin, and inhibitors of these isoenzymes do not substantially affect it. Rosuvastatin could be a first-line option for patients requiring a reduction of 50% or more to reach the LDL goal of the National Cholesterol Education Program Adult Treatment Panel III. Rosuvastatin monotherapy may allow patients to achieve this LDL goal earlier, and it may help them avoid combination therapy or potential adverse effects of high-dose statin therapy. However, because cardiovascular disease morbidity and mortality data are lacking for rosuvastatin (but available for all other marketed statins) and because its postmarketing data are limited, rosuvastatin should be reserved for patients requiring an LDL reduction of 50% or less who cannot reach the recommended goal with other statins because of adverse effects, drug interactions, or cost.

Observational studies have shown that elevated total cholesterol and low-density lipoprotein cholesterol (LDL) levels have a direct relationship with coronary heart disease (CHD) and that high-density lipoprotein cholesterol (HDL) has an inverse relationship to CHD.[1,2,3] Of all the drug classes available to treat hyperlipidemia, the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, commonly known as statins, have the greatest LDL-lowering effect. Several studies have demonstrated the beneficial role statins play in the primary and secondary prevention of CHD.[4,5,6,7,8,9,10]

Despite the widespread use of statins, many patients do not reach the LDL goal defined in the National Cholesterol Education Program Adult Treatment Panel (ATP) III.[11,12,13] This observation is of particular concern in very high-risk patients, who include those with CHD plus diabetes mellitus, those with metabolic syndrome, or those who are cigarette smokers. Some have suggested that these very high-risk patients should achieve an LDL level of less than 70 mg/dl to further decrease their risk of cardiovascular morbidity and mortality.[14] In addition, cardiovascular morbidity and mortality are decreased in patients with CHD who are treated early with high-dose statin therapy. However, this therapy has been associated with myopathy and increased elevations in liver transaminase levels.[15,16]

In August 2003, the United States Food and Drug Administration (FDA) approved rosuvastatin calcium (Crestor; AstraZeneca Pharmaceuticals, Wilmington, DE) as an adjunct to diet in patients with primary hypercholesterolemia, mixed dyslipidemia, or Fredrickson type IV hypercholesterolemia. Rosuvastatin is also approved for use as an adjunct to other lipid-lowering treatments in patients with homozygous or heterozygous familial hypercholesterolemia.


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