Patients with high levels of low-density lipoprotein cholesterol ( LDL-C ) might not tolerate HMG-CoA reductase inhibitors, also known as statins, because of adverse effects and might not respond well enough to non-statin lipid-lowering therapies to meet LDL-cholesterol goals.

The purpose of a study, performed by a team of researchers at The Cholesterol Center, Jewish Hospital, Cincinnati, was to assess the acceptability, effectiveness, and safety profile of Rosuvastatin ( Crestor ) 5 and 10 mg/d in consecutively referred patients with primary high LDL-cholesterol, who were unable to tolerate other statins because of myalgia and, subsequently in some cases, unable to reach LDL-cholesterol goals with non-statin lipid-lowering therapies.

This prospective, open-label pilot study was conducted in patients aged 38 to 80 years with primary high LDL-cholesterol ( mean, 177 mg/dL ).
Patients were instructed in the National Cholesterol Education Program Adult Treatment Panel III ( NCEP ATP III ) therapeutic lifestyle changes diet.

Rosuvastatin 5 mg/d was administered to patients categorized by NCEP ATP III risk stratification as moderately high risk, and Rosuvastatin 10 mg/d was administered to patients categorized as high or very high risk.

End points included acceptability ( assessed using patient-initiated discontinuation of Rosuvastatin ), effectiveness ( absolute and percentage reductions in LDL-cholesterol and triglycerides ), and safety profile ( aspartate and alanine aminotransferases [ AST and ALT, respectively ] >3 times the laboratory upper limit of normal [ x ULN ] or elevations in creatine kinase [ CK ] >10 x ULN ).

A total of 61 patients were enrolled ( 41 women, 20 men; mean age, 60 years; 5-mg/d dose, 25 patients; 10-mg/d dose, 36 patients ).

Myalgia had caused 50 patients to previously discontinue treatment with Atorvastatin; 30, Simvastatin; 19, Pravastatin; 5, Fluvastatin; 2, Ezetimibe/Simvastatin; and 1, Lovastatin.
Eighteen patients subsequently failed to reach LDL-cholesterol goals with non-statin lipid-lowering therapies alone ( Colesevelam, 10 patients; Ezetimibe, 8; Niacin extended release, 2; and Fenofibrate, 1 ).

After a median treatment duration of 16 weeks, Rosuvastatin 5 mg/d plus diet was associated with a mean decrease from baseline in LDL-cholesterol of 75 mg/dL ( - 42%; P<0.001 vs baseline ).

After a median treatment duration of 44 weeks, Rosuvastatin 10 mg/d plus diet was associated with a mean decrease from baseline in LDL-cholesterol of 79 mg/dL ( - 42%; P<0.001 vs baseline ).

Of the 61 patients, 1 receiving the 10-mg/d dose discontinued Rosuvastatin treatment because of unilateral muscular pain after 4 weeks; no AST or ALT levels were > 3 x ULN, and no CK levels were > 10 x ULN.

“ In these 61 hypercholesterolemic patients unable to tolerate other statins and, subsequently in some cases, unable to meet LDL-cholesterol goals while receiving non-statin lipid-lowering monotherapy, these preliminary observations suggest that Rosuvastatin at doses of 5 and 10 mg/d plus diet was well tolerated, effective, and had a good safety profile, “ the authors conclude.

Source: Clinical Therapeutics, 2006


XagenaMedicine2006