LONG-TERM EFFICACY WITH FLUVASTATIN AS MONOTHERAPY AND COMBINED WITH CHOLESTYRAMINE (A 156-WEEK MULTICENTER STUDY)

Fluvastatin monotherapy vp to 40 mg/day over 52 weeks in patients with primary hypercholesterolemia decreased plasma low density lipoprotein cholesterol (LDL-C) by 28%, with varying decreases in plasma triglyce rides and increases in high density lipoprotein cholesterol (HDL-C). P atients completing the 52-week study participated in a further trial t o assess whether the efficacy of fluvastatin (20-40 mg/day), either as monotherapy or in combination with cholestyramine (CME; 4-16 g/day), taken at least 4 hours prior to fluvastatin, is sustained for up to 3 years. Patients were assessed every 12 weeks on average for safety and efficacy, the latter being calculated as a percent change from baseli ne of lipids or lipoproteins. During the second year (endpoint up to w eek 104), 147 patients received monotherapy (estimated mean dose, 30.2 mg/day) and 127 received additional CME (38.1 mg/day fluvastatin plus 10.1 g/day CME). During the third year (endpoint vp to week 156), 140 patients received monotherapy (32.5 mg/day) and 67 received additiona l CME (39.3 mg/day fluvastatin plus 10.3 mg/day CME). Statistically si gnificant reductions in mean total cholesterol and LDL-C and increases in mean HDL-C were achieved in both treatment groups and maintained t hroughout the study. A significant reduction in triglyceride levels wa s only observed at the second year endpoint in patients receiving mono therapy (-10.0%). During the extension trial, 19 patients experienced serious adverse events: 1 cholestatic hepatitis, 2 myocardial infarcti ons (1 fatal), 1 myeloma, 2 non-Hodgkin lymphomas, 1 amyotrophic later al sclerosis, 4 angina pectoris, 1 cataract, 1 hypothyroidism, 1 tuber cular spondylodiscitis, 1 transient ischemic attack, 1 pulmonary hyper tension, 1 mammary carcinoma, 1 bladder carcinoma, and 1 benign adenoi d dysplasia of the thyroid. Nonserious adverse events led to premature discontinuation in 18 patients receiving monotherapy and 3 receiving combined therapy. Other than the case of cholestatic hepatitis, no adv erse events or rare observations of notable biochemical or hematologic abnormalities were considered to be related to treatment with the stu dy drugs. These data confirm the long-term safety, tolerability, and s ustained efficacy of fluvastatin less than or equal to 40 mg/day, with and without CME.