Effect of rosuvastatin on low-density lipoprotein cholesterol in patients with hypercholesterolemia - Effect of rosuvastatin on low-density lipoprotein cholesterol in patients with hypercholesterolemia

Aug 08, 2003
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Date Published:
01/01/2003
Date Updated:
08/08/2003
Original Posted Date:
08/08/2003
References

Description:

The goal of the trial was to assess the dose-response efficacy and safety of rosuvastatin in patients with mild to moderate hypercholesterolemia.

Study Design

Study Design:

Patients Screened: 594
Patients Enrolled: 206
Mean Follow Up: 6 weeks
Mean Patient Age: 56 years (range 24 to 70)
Female: 37%

Patient Populations:

Men age 18-70 years and postmenopausal women age 50-70 years, fasting LDL cholesterol levels >160 mg/dl and <240 mg/dl, triglyceride levels <300 mg/dl, and body mass index 30 kg/m2

Exclusions:

Cholesterol-lowering drugs in four weeks prior to the run-in period, active arterial disease, history of malignancy, uncontrolled hypertension, diabetes mellitus, uncontrolled hypothyroidism, homozygous familial hypercholesterolemia, active liver disease or hepatic dysfunction, serum creatinine level >180 µmol/L, and serum creatine kinase level >3 times the upper limit of normal

Primary Endpoints:

Percent change from baseline to week six in LDL cholesterol

Secondary Endpoints:

Estimation of the dose-response relation between rosuvastatin dose and percent changes in total cholesterol and apolipoprotein (apo) B levels from baseline versus placebo; changes from baseline for HDL cholesterol, triglycerides, apo A-I, lipoprotein(a), and lipid ratios (total cholesterol:HDL cholesterol, LDL cholesterol:HDL cholesterol, non-HDL cholesterol:HDL cholesterol, and apo B:apo A-I ratios) versus placebo

Drug/Procedures Used:

Following a six-week dietary run-in period, 142 patients in the first trial were randomized to double-blind placebo or rosuvastatin 1, 2.5, 5, 10, 20, or 40 mg or open-label atorvastatin 10 or 80 mg once daily for six weeks.

In a second study, designed to extend the rosuvastatin dose range, 64 patients were randomized to double-blind placebo or rosuvastatin 40 or 80 mg (1:1:2 ratio) for six weeks. Placebo and rosuvastatin data from both studies were combined for analysis of lipid effects, but no statistical comparison of atorvastatin arms with placebo or rosuvastatin was performed.

Principal Findings:

Compared with placebo, all dose levels of rosuvastatin were associated with significant reductions in low-density lipoprotein (LDL) cholesterol (p<0.001), with reductions ranging from 34% at rosuvastatin 1 mg to 65% at rosuvastatin 80 mg compared with 3.6% for placebo, with 64% and 90% of the reduction occurring during weeks one and two of treatment, respectively. Dose-dependent reductions were also observed in total cholesterol (from 24% to 47%) and apolipoprotein B (from 29% to 55%) with rosuvastatin (p<0.001).

High-density lipoprotein (HDL) cholesterol was significantly increased in the 80 mg dose arm (12.9% vs. 3.6% for placebo, p<0.05), but differences at other doses were not significant compared with placebo. Triglyceride decreases were larger compared with placebo in the 5, 40, and 80 mg arms, but not at the other doses. Adverse event rates were similar across placebo and active treatments. No significant increases in alanine aminotransferase or creatine kinase occurred in any patients.

Interpretation:

Among patients with mild to moderate hypercholesterolemia, treatment with rosuvastatin was associated with a significant, dose-dependent reduction in the primary endpoint of change from baseline to week six in LDL cholesterol. These studies were the first randomized, multicenter trials of the novel inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase rosuvastatin.

The majority of reduction in LDL occurred early (within the first two weeks of therapy), with no additional increase in adverse events compared with placebo, and no increases in liver enzymes. The overall sample size of the study was relatively small, and further larger trials are warranted.

References:

Olsson AG, Pears J, McKellar J, Mizan J, Raza A. Effect of rosuvastatin on low-density lipoprotein cholesterol in patients with hypercholesterolemia. Am J Cardiol 2001;88:504-8.

Keywords: Fluorobenzenes, Creatine Kinase, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Pyrimidines, Heptanoic Acids, Hypercholesterolemia, Pyrroles, Lipoproteins, LDL, Cholesterol, Oxidoreductases, Body Mass Index, Triglycerides, Fasting, Sulfonamides


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