Bruce D. Behounek

Efficacy and Safety of Pravastatin in the Long-term Treatment of Elderly Patients With Hypercholesterolemia

PURPOSE Elevated cholesterol levels are a major risk factor for coronary heart disease, which remains a significant problem in patients beyond age 65 years. Because drug therapy for the control of hypercholesterolemia in elderly patients is frequently considered to be indicated, we investigated the efficacy and safety of pravastatin in the treatment of elderly subjects with primary hypercholesterolemia. PATIENTS AND METHODS In this 96-week, multicenter, double-blind, placebo-controlled study, 142 subjects (95 women, 47 men) 64 to 90 years of age with elevated cholesterol levels despite dietary intervention were randomized to receive pravastatin 20 mg at bedtime or matching placebo (2:1). Dosage could be doubled after 8 weeks, a bile acid-binding resin could be added after 16 weeks, and nicotinic acid or probucol could be added after 32 weeks, as needed, to adequately lower the low-density lipoprotein cholesterol (LDL-C) levels. RESULTS Significant reductions in the levels of LDL-C (-30.9%), total cholesterol (Total-C; -21.9%), and triglycerides (TG; -16.7%) and significant increases in the levels of high-density lipoprotein cholesterol (HDL-C; 11.3%) were noted in the group receiving pravastatin treatment at 16 weeks (P < or = 0.001 compared with baseline, P < or = 0.01 compared with placebo). The cholesterol-lowering effects of pravastatin were sustained throughout the 96 weeks of the trial. Pravastatin was well tolerated, with an overall incidence of adverse events nearly identical to that of placebo. CONCLUSIONS In this study, pravastatin was well tolerated and effective in lowering LDL-C, Total-C, and TG and in raising HDL-C during long-term treatment of elderly patients with primary hypercholesterolemia.

Efficacy and safety of pravastatin in the treatment of patients with type I or type II diabetes mellitus and hypercholesterolemia

PURPOSE Patients with type I and type II diabetes mellitus have an increased risk of coronary heart disease. In many diabetics, hypercholesterolemia is present and further exacerbates this risk. We investigated the efficacy and safety of pravastatin in the treatment of patients with type I or type II diabetes mellitus and hypercholesterolemia. PATIENTS AND METHODS In this 24-week, multi-center, double-blind, placebo-controlled study, 94 patients (45 men, 49 women), 18 to 70 years of age, with type I or type II diabetes mellitus and hypercholesterolemia (fasting plasma low-density lipoprotein cholesterol [LDL-C] levels > 150 mg/dL and above the 75th percentile for the US population by age and gender) were randomized to receive pravastatin 20 mg hs or matching placebo. Two patients were randomized to treatment with drug for every 1 randomized to placebo. The dose could be doubled after 10 weeks, and cholestyramine or colestipol could be added after 18 weeks, as needed, to attempt to lower the LDL-C levels to below the 50th percentile for the US population. RESULTS Significant reductions in LDL-C (-27.6%), total cholesterol (-22.1%), very-low-density lipoprotein cholesterol (-22.6%), and triglycerides (-12.8%) (P < or = 0.001 versus placebo for all reductions), and significant increases in high-density lipoprotein cholesterol (4.4%) (P < or = 0.05 versus placebo) were noted in the pravastatin treatment group (average dose 29.5 mg) at 16 weeks. The beneficial lipid-lowering effects of pravastatin were maintained throughout the 24 weeks of the study. Pravastatin was well tolerated, and the frequency of side effects was similar in the pravastatin and placebo groups. No clinically significant changes in the control of diabetes, as assessed by fasting blood glucose levels and glycosylated hemoglobin measurements, were seen during this study. CONCLUSION The results of this study demonstrate that pravastatin is well tolerated and effective in lowering total cholesterol and LDL-C in patients with type I or type II diabetes mellitus and hypercholesterolemia.

Effect of Pravastatin in the Treatment of Patients with Type III Hyperlipoproteinemia.

ObjectiveTo determine the efficacy and safety of pravastatin in the treatment of subjects with Type III hyperlipoproteinemia. DesignRandomized, double-blind, placebo-controlled, crossover study. SettingFour lipid research clinics in the United States. PatientsTwenty subjects between 18 and 70 years old with three diagnostic features of Type III hyperlipoproteinemia: very-low-density lipoprotein cholesterol (VLDL-C)/total plasma triglyceride ratio in excess of 0.30; beta-migrating VLDL pattern on agarose-gel electrophoresis; and the homozygous apolipoprotein E phenotype E2/E2. After 4 weeks of dietary control, the subjects were eligible if their mean plasma total cholesterol level was at least 250 mg/dL and mean plasma triglyceride level was at least 220 mg/dL. InterventionsSubjects were randomly assigned to pravastatin 40 mg hs or placebo hs at the start of the first 6-week double-blind treatment period. After completing this phase, subjects entered a 4-week placebo/drug washout phase before crossing over to the opposite treatment for the second 6-week double-blind treatment period. MeasurementsPlasma VLDL-C and low density lipoprotein cholesterol (LDL-C) after ultracentrifugation and total triglyceride, cholesterol and high-density lipoprotein cholesterol (HDL-C) after 6 weeks of treatment; adverse clinical events and abnormal laboratory results. ResultsAfter 6 weeks of pravastatin therapy, plasma levels of VLDL-C and LDL-C decreased 49% and 39%, respectively (p < 0.01 vs. placebo). Total cholesterol and triglyceride concentrations decreased 36% and 22%, respectively (p < 0.001 vs. placebo). Levels of HDL-C increased 8% (p < 0.01 vs. placebo). Pravastatin was tolerated well. One marked laboratory abnormality, an asymptomatic elevation of creatine phosphokinase, resolved upon completing pravastatin treatment. ConclusionsPravastatin lowers plasma VLDL-C, LDL-C, total cholesterol, and triglyceride and raises HDL-C in subjects with Type III hyperlipoproteinemia. The safety profile is excellent. Pravastatin reductase inhibitor therapy affords a useful approach to the management of Type III or remnant removal disease.