Effect of a new HMG-CoA reductase inhibitor, atorvastatin, on lipids, apolipoproteins and lipoprotein particles in patients with elevated serum cholesterol and triglyceride levels
Introduction
Hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are most often prescribed for lowering plasma cholesterol levels in those patients with primary hypercholesterolemia. These agents, including lovastatin, pravastatin, simvastatin and fluvastatin very effectively treat patients with primary hypercholesterolemia, but have a limited ability to decrease triglyceride (TG) levels 1, 2, 3. For the patient presenting with concomitant elevations in total cholesterol (TC) and TG levels, treatment options are limited. The co-administration of an HMG-CoA reductase inhibitor with an agent such as nicotinic acid or a fibric acid derivative can often reduce both cholesterol and triglycerides in this population; however, this combination therapy results in higher cost to the patient, more difficulties with compliance, and an increased risk of myositis and renal failure [4].
It has recently been shown that atorvastatin (lipitor), a newly developed HMG-CoA reductase inhibitor, reduces total plasma cholesterol up to 45% and LDL-cholesterol up to 60% in a dose dependent manner when administered to patients with primary hypercholesterolemia [5]. Additionally, the triglyceride lowering property of atorvastatin has been demonstrated in patients with primary hypercholesterolemia 5, 6, 7, 8and in those with primary hypertriglyceridemia [9]. Because of these differential effects of HMG-CoA reductase inhibitors on the concentrations of cholesterol-rich and triglyceride-rich lipoproteins and because of the already documented substantial triglyceride-lowering effect of atorvastatin, it was of considerable interest and importance to further evaluate atorvastatin's effect on cholesterol-rich and triglyceride-rich lipoprotein particles in a dyslipidemic population that would benefit from this dual effect.
Section snippets
Patients
Seven centers in Canada participated in this open-label trial. Eligible patients were aged 18–80 years old with a body mass index ≤32 kg/m2 (Table 1). Patients were ineligible if they were pregnant or nursing, had active liver disease or hepatic dysfunction; nephrotic syndrome or renal insufficiency; uncontrolled hypertension, hypothyroidism or diabetes; were consuming more than 10 alcoholic drinks per week, or had a history of drug abuse. Additionally, patients were screened for Type III
Patient characteristics and disposition
A total of 47 patients (33 men, 14 women) were treated with atorvastatin. Forty-six patients had data for Period 1 and 45 had data for Period 2. Ninety-four percent of the patients were white and the mean patient age was 50 years. Based on investigator assessments (pill count), atorvastatin compliance ranged from 93–100%. According to their baseline lipid levels, patients were categorized as having combined hyperlipidemia (CHL) (LDL≥3.5 mmol/l (134 mg/dl) and TG≥2.3 mmol/l (200 mg/dl)) or
Discussion
Results of this study demonstrate that atorvastatin has the capacity to lower significantly the plasma concentrations of the characteristic cholesterol-rich and triglyceride-rich lipoprotein constituents in patients with elevated levels of both cholesterol and triglycerides. It has been previously reported that in CHL patients, 10 or 20 mg atorvastatin resulted in significantly greater reductions in LDL-C, apo B, TC, LDL-apo B and LpB compared to 300 mg fenofibrate treatment [22]. The degree of
Acknowledgements
This study was supported by Parke-Davis Pharmaceutical Research, Division of Warner Lambert Co, Ann Arbor, Mich. The authors would like to thank R.E. Laskey, PhD, for assistance in manuscript preparation, and C. Knight-Gibson, J.D. Fesmire, C. Quiroga and S. Bryant for their technical assistance.
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