Safety and Efficacy of Pravastatin 40 mg, 80 mg, and 160 mg per Day - Safety and Efficacy of Pravastatin 40 mg, 80 mg, and 160 mg per Day

Description:

The goal of the trial was to evaluate the efficacy, safety, and tolerability of pravastatin for six weeks at doses of 40, 80, or 160 mg once daily for cholesterol-lowering in patients with primary hypercholesterolemia.

Study Design

Study Design:

Patients Screened: 259
Patients Enrolled: 189
Mean Follow Up: 6 weeks

Patient Populations:

Age 24-65 years, primary hypercholesterolemia (LDL-cholesterol ≥160 mg/dl and triglycerides ≤500 mg/dl), and no history of cardiovascular disease

Exclusions:

Cardiovascular disease, symptomatic cerebrovascular disease, and the current use of any cholesterol-lowering agents and nonstudy drugs that affect lipid metabolism

Drug/Procedures Used:

Previous lipid-lowering medication was discontinued and patients entered a four-week dietary stabilization period, followed by a four-week single-blind placebo lead-in period. To enter the randomized study, patients had to consume 80-120% of the placebo study drug during the lead-in period.

Patients were randomized to either placebo (n=46), pravastatin 40 mg, pravastatin 80 mg, or pravastatin 160 mg (n=143 for all pravastatin arms) taken as four matching tablets at bedtime for six weeks. Fasting lipids were measured at entry and weeks two, four, and six.

Concomitant Medications:

No other lipid-lowering medication was allowed.

Principal Findings:

Low-density lipoprotein (LDL) cholesterol at six weeks was significantly reduced in the pravastatin arms compared with baseline by 29% with 40 mg (p<0.001), 37% with 80 mg (p<0.001), and by 45% with 160 mg (p<0.001), but no significant difference occurred in the placebo arm (-0.7, p=NS). Both total cholesterol (p<0.001) and triglycerides (p<0.001) also decreased in a dose-dependent manner in the pravastatin arms. There was no dose-dependent increase in high-density lipoprotein (HDL) cholesterol (p=0.47).

On-treatment adverse events were similar for placebo (45.7%), pravastatin 40 mg (34.8%), pravastatin (51%) 80 mg, and pravastatin 160 mg (62.5%). No patients had any test of liver function >3x upper limit of normal or were discontinued from any study group due to liver enzyme abnormalities. Also, no deaths or serious adverse events were reported.

Interpretation:

Among patients with primary hypercholesterolemia, treatment with pravastatin for six weeks was associated with a dose-dependent reduction in both LDL and total cholesterol at six weeks. This dose-dependent reduction occurred without an increase in adverse events. Prior large-scale trials such as LIPID and PROSPER have shown a reduction in mortality associated with pravastatin 40 mg over placebo.

References:

Rosenson RS, Bays HE. Results of two clinical trials on the safety and efficacy of pravastatin 80 and 160 mg per day. Am J Cardiol 2003;91:878-81.

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

Keywords: Hyperlipidemias, Cholesterol, LDL, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypercholesterolemia, Single-Blind Method, Lipoproteins, LDL, Pravastatin, Hypolipidemic Agents, Liver, Cholesterol, HDL, Diet, Lipoproteins, HDL, Triglycerides, Fasting


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