FLUVASTATIN IN PRIMARY HYPERCHOLESTEROLEMIA - EFFICACY AND SAFETY IN PATIENTS AT HIGH-RISK - AN ANALYSIS OF A CLINICAL-TRIAL DATABASE

Patients with primary hypercholesterolemia and established coronary ar tery disease (CAD) with additional associated risk factors for atheros clerosis are considered for lipid-lowering drug therapy at lower level s of total and/or low-density lipoprotein cholesterol (LDL-C) than are patients with isolated hypercholesterolemia. As regards prevention of cardiovascular morbid events, high-risk patients are expected to rece ive the most benefit from lipid-lowering treatment. Thus, it is of int erest to evaluate the efficacy, safety, and tolerability of the new li pid-lowering agent fluvastatin, a new, wholly synthetic 3-hydroxy-3-me thylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, in patients at high risk. A retrospective analysis was based on data from controlled clinical trials in which 1,815 patients were treated with fluvastatin at a daily dose of greater than or equal to 20 mg and 783 patients rec eived placebo. Of the fluvastatin-treated patients, 328 (18.1%) had CA D compared with 136 (17.4%) patients taking placebo. Within these grou ps, 186 fluvastatin patients and 75 placebo patients had at least one of the following additional risk factors: hypertension, obesity, and/o r fasting blood glucose levels above the upper limit of normal (ULN). Patients at high risk, as defined above, were compared with patients w ithout CAD or any risk factors (fluvastatin, n = 837; placebo, n = 375 ). The effect of 40 mg of fluvastatin on LDL and high-density Lipoprot ein cholesterol (HDL-C), and triglycerides tended to be enhanced in pa tients at high risk (HR) compared with those at low risk (LR). Changes from baseline in HR patients were: LDL-C, - 26.6%; HDL-C, 6.4%; trigl ycerides, - 13%. Changes in LR patients were: LDL-C, - 24.8%; HDL-C, 4 .4%; triglycerides, - 6%. All of these changes were highly significant (0.001 < p < 0.01). No patient in the HR group experienced a confirme d (measured on two consecutive occasions) increase > 3 x ULN in aspart ate (ASAT) or alanine (ALAT) aminotransferases, nor any notable increa ses in creatine kinase > 10 x ULN. The tolerability of fluvastatin, as assessed by analysis of adverse events, was not consistently influenc ed by concomitant high risk. This exploratory analysis of the efficacy and safety profile of fluvastatin in patients at high risk for athero sclerosis suggests that such treatment is efficacious, safe, and well tolerated. The observed tendency toward an improved efficacy in the hi gh-risk group will need further confirmation using data from prospecti ve studies in such patients.