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
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.
Patients Screened: 259
Patients Enrolled: 189
Mean Follow Up: 6 weeks
Age 24-65 years, primary hypercholesterolemia (LDL-cholesterol ≥160 mg/dl and triglycerides ≤500 mg/dl), and no history of cardiovascular disease
Cardiovascular disease, symptomatic cerebrovascular disease, and the current use of any cholesterol-lowering agents and nonstudy drugs that affect lipid metabolism
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.
No other lipid-lowering medication was allowed.
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.
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.
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, Hypertriglyceridemia, 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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