Fluvastatin titrate-to-goal clinical practice study: Interim results

Abstract

Fluvastatin, the newest addition to the class of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, is structurally different from the other agents. Fluvastatin is the first entirely synthetic HMG-CoA reductase inhibitor and, compared with the other drugs of its class, has a distinct pharmacologic profile, including short systemic exposure time (half-life of 1.2h), no active circulating metabolites, and a high degree of protein binding (98%). Fluvastatin is targeted to the liver, with a high rate of absorption (95%). The clinical development of fluvastatin has involved primarily adult patients whose cholesterol levels are in the 95th percentile of the adult population in the United States. This population represents fewer than 10% of all adults with hyper-cholesterolemia. Thus, the Fluvastatin Titrate-to-Goal Clinical Practice Study was undertaken to evaluate the efficacy and safety of fluvastatin in patients similar to those managed in clinical practices. The goal was to evaluate the efficacy and safety of fluvastatin 20 or 40 mg/day as monotherapy in patients with moderate hypercholesterolemia (type IIa or IIb), irrespective of age, race, gender, or presence of multiple other risk factors (i.e., hypertension and angina) for coronary heart disease (CHD) or established CHD. The study sample included 1,019 men and women, aged 18 to 75 years, who had a diagnosis of hypercholesterolemia: low-density lipoprotein cholesterol (LDL-C)≥160 mg/dl and triglyceride ≤350 mg/dl despite dietary intervention. These criteria, defined by the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, are assigned to the high-risk LDL-C classification. Interim study results indicate that significant reductions in levels of total cholesterol and LDL-C were achieved within 6 weeks of treatment with fluvastatin at a dosage of 20 mg/day. This effect was sustained at Week 12, with a mean reduction in total cholesterol levels of 15%, an LDL-C reduction of 21%, a triglyceride reduction of 11%, and an increase in high-density lipoprotein cholesterol levels of 4%. After 12 weeks of therapy with fluvastatin, the NCEP target goal (LDL-C < 160 mg/dl) was reached in 83% of all study patients as well as in 84% with hypertension, 85% of those with CHD, and 88% with angina. Headache, upper respiratory infection, a pepsia were the most frequently observed adverse effecting fluvastatin treatment. No significant changes in liv tion tests were seen in patients receiving fluvastati baseline to Week 12.