Effects of rosuvastatin and atorvastatin compared over 52 weeks of treatment in patients with hypercholesterolemia - Effects of rosuvastatin and atorvastatin compared over 52 weeks of treatment in patients with hypercholesterolemia

Description:

The goal of the trial was to compare treatment with rosuvastatin versus atorvastatin in reducing low-density lipoprotein cholesterol (LDL-C) and achieving LDL-C goals among patients with primary hypercholesterolemia.

Study Design

Study Design:

Patients Screened: 1,521
Patients Enrolled: 412
Mean Follow Up: 52 weeks
Mean Patient Age: mean age 56-58 years
Female: 43%

Patient Populations:

Age ≥18 years; and hypercholesterolemia during the lead-in period, defined as fasting LDL-C level of 160 to <250 mg/dl (4.14 and <6.5 mmol/l), fasting triglyceride levels ≤400 mg/dl (≤4.5 mmol/l), and an Eating Pattern Assessment Tool (EPAT) score ≤28

Primary Endpoints:

Percentage change from baseline in LDL-C levels at 12 weeks

Secondary Endpoints:

Changes in LDL-C at 52 weeks; percentage changes in total cholesterol, HDL-C, triglycerides, and lipoprotein ratios (LDL-C/HDL-C, total cholesterol/HDL-C, non-HDL-C/HDL-C), Apo B, Apo A-I, and Apo B/Apo A-I ratio at 12 and 52 weeks; and proportions of patients meeting ATP-II and European LDL-C goals at 12 and 52 weeks

Drug/Procedures Used:

Eligible patients entered the six-week dietary lead-in period and all cholesterol-lowering drugs, dietary supplements, and food additives were discontinued. After the lead-in period, eligible patients were randomized to rosuvastatin 5 mg/day (n=138), rosuvastatin 10 mg/day (n=134), or atorvastatin 10 mg/day (n=140) for 12 weeks.

After the 12-week fixed-dose period, study medication could be doubled (up to 80 mg) at the medical discretion of the investigator at each eight-week visit if National Cholesterol Education Program Adult Treatment Panel II (ATP-II) LDL-C goals were not met.

Principal Findings:

LDL-C was reduced at 12 weeks compared with baseline in all three arms, although both doses of rosuvastatin were associated with larger reductions in LDL-C versus atorvastatin (46% for 5-mg and 50% for 10-mg rosuvastatin vs. 39%, both p<0.001). Likewise, total cholesterol reductions at 12 weeks were greater with both 5-mg (-32%) and 10-mg (-35%) rosuvastatin compared with atorvastatin (-28%; p<0.001 for both), although there was no difference in high-density lipoprotein (HDL) changes (+6%, +8%, and +6%, respectively, p=NS) or triglycerides (-15%, -19%, -16%, p=NS). ATP-II and European LDL-C goals at 12 weeks were achieved more frequently in both rosuvastatin dosages compared with atorvastatin (86% and 89% vs. 73% for ATP-II; and 75%, and 86% vs. 55%, respectively).

Similar benefit in LDL-C reduction was observed at 52 weeks (-47% and -53% vs. -44%, p<0.05 and p<0.001). At 52 weeks, 82% of patients treated with 10-mg rosuvastatin achieved their LDL-C goal at the starting dosage without the need for titration, compared with 59% of patients treated with atorvastatin. Both treatments were well tolerated over 52 weeks, with myalgia and gastrointestinal complaints the most frequent treatment-related adverse events.

Interpretation:

Among patients with primary hypercholesterolemia, rosuvastatin was associated with a reduction in the primary endpoint of LDL-C at 12 weeks compared with atorvastatin, with similar results through one year. The majority of patients in all three treatment arms achieved target LDL-C levels within 12 weeks of treatment, indicating the effectiveness of statin therapy.

Of note, more rosuvastatin-treated patients in both groups achieved target LDL-C levels at starting dosages without the need for upward titration during the one-year follow-up, a potential benefit compared with other existing lipid-lowering therapies. Further trials are warranted to determine how rosuvastatin will compare with other lipid-lowering therapies.

References:

Olsson AG, Istad H, Luurila O, et al., for the Rosuvastatin Investigators Group. Effects of rosuvastatin and atorvastatin compared over 52 weeks of treatment in patients with hypercholesterolemia. Am Heart J 2002;144:1044-51.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Diet

Keywords: Fluorobenzenes, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Pyrimidines, Heptanoic Acids, Hypercholesterolemia, Food Additives, Pyrroles, Cholesterol, Dietary Supplements, Triglycerides, Fasting, Myalgia, Sulfonamides


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