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Trial of Pravastatin in Primary Isolated Hypercholesterolemia - RED-LIP
Description:
RED-LIP was an open, multicenter, prospective trial, evaluating safety and efficacy of pravastatin 10-40 mg once daily for three months in patients with primary isolated hypercholesterolemia.
Hypothesis:
After three months, pravastatin therapy will be associated with lowering of total cholesterol (TC), calculated low-density lipoprotein (LDL) and serum triglycerides (TGs), and an increase in high-density lipoprotein (HDL).
Study Design
Study Design:
Patients Enrolled: 1,111
Mean Follow Up: Three months
Mean Patient Age: Mean age 56 years
Female: 51
Patient Populations:
TC >250 mg/dl, and no significant response to three months of dietary counseling
Exclusions:
TGs >300 mg/dl, severe obesity, or therapy with other lipid-lowering drugs
Primary Endpoints:
Change in TC, LDL, HDL, and TG levels at the end of the study
Secondary Endpoints:
Incidence of pravastatin-related adverse events
Drug/Procedures Used:
After an initial three-month dietary counseling period, patients who were unable to achieve a TC level <250 mg/dl, were enrolled in the study.
Treatment was initiated with pravastatin 10 mg once daily. Inadequate response to pravastatin was defined as a reduction in TC of less than 10%. After 4-8 weeks of therapy, patients with inadequate response to the initial dose had their dose increased to 20 mg or 40 mg once daily. Lipid profile was measured at the beginning of the study, and at 4, 8, and 12 weeks after initiation of therapy.
Serum creatine kinase (CK) levels and levels of liver transaminases were measured at the beginning of the study and 12 weeks after initiation of therapy. Adverse reactions were recorded at regular intervals throughout the study.
Principal Findings:
A total of 1,111 patients were enrolled in the study; 396 patients were excluded from efficacy analysis because of protocol violation at baseline or during the study. Primary analysis was thus carried out using data from 715 patients.
Baseline TC levels were 317.5 ± 41.0 mg/dl in males, and 21.5 ± 43.5 mg/dl in females.
At the end of the study, pravastatin dosage was 10 mg/day in 67% of the patients and 20 mg in 20%.
Therapy with pravastatin was associated with lowering of TC by 23.8% (p<0.001), calculated LDL by 31.9% (p<0.001), and TGs by 16.9% (p<0.001). Therapy with pravastatin was also associated with an increase in HDL of 15% (p<0.001).
Subgroup analysis demonstrated no difference in number of responders, or in the degree of lipid alterations between men and women, and between patients with and without coronary artery disease.
There were two deaths in the study population, both thought to be unrelated to the study drug. No serious adverse event was attributable to the drug. Three patients had three-fold elevations of liver transaminases above normal. In two patients, a four-fold increase in CK above normal was observed.
Interpretation:
Among a heterogeneous hypercholesterolemic population, treatment with pravastatin 10 mg once daily was associated with a substantial improvement in the lipid profiles in two-thirds of the population. The drug was well-tolerated in most patients. Several studies since then have correlated the decrease in TC and LDL levels with a reduction in the risk of adverse cardiovascular events.
References:
Sinzinger H, Pirich C. The RED-LIP study--pravastatin in primary isolated hypercholesterolemia--an open, prospective, multicenter trial. Wien Klin Wochenschr 1994;106:721-7.
Keywords: Coronary Artery Disease, Creatine Kinase, Cholesterol, LDL, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Liver, Pravastatin, Transaminases, Counseling, Cholesterol, HDL, Hypercholesterolemia, Triglycerides
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