Abstract 4193: A Randomized, Double-blind, Double-dummy, Comparison of Efficacy and Tolerability of Fluvastatin XL alone, Ezetimibe alone and the Combination, in Patients with a History of Muscle Related Side Effects with other Statins

Abstract

Reduction of LDLC is the core of cardiovascular disease (CVD) prevention. Trials showing the lower the LDLC the lower the CVD risk have led to revision of the NCEP guidelines for high risk patients. Statins, the most effective class for achieving LDLC reduction, are generally well tolerated and serious side effects are rare. However in clinical practice muscle related side effects (MRSE), such as pain, cramps and weakness are more common than reported in clinical trials. A recent observational study of nearly 8,000 patients in primary care practice reported 10.5% MRSE with statins. MRSE were the major reason for discontinuation. Inability to use statins leaves physicians and patients minimal ability to achieve LDLC goals at any risk level. Fluvastatin XL (FXL) has a number of unique pharmacological features that suggest it would have a lower propensity for MRSE. The present trial, is the first randomized, double dummy, controlled trial done in patients with statin associated MRSE, to test the hypothesis that in such patients FXL 80 mg would be as well tolerated as a non-statin lipid lowering agent. Ezetimibe (EZE) 10 mg, a cholesterol absorption inhibitor, was selected as a widely used, effective well tolerated agent. The study randomized 199 mostly high-risk subjects with a history of statin related MRSE in 27 centers. After 4 week diet only lead-in patients were randomized to 12 week treatment with FXL + placebo (Pbo) EZE; EZE + Pbo FLX or FLX + EZE. Results are shown below: The present study demonstrates that patients with statins related MRSE tolerate FXL, either alone or as combination therapy with EZE, with MSRE side effects no different from that of EZE alone. Few patients at high risk for CVD reach LDLC goal with EZE alone, one third do with FLX and nearly 4 of 5 do so with FLX + EZE. With 1–2 million patients estimated to have discontinued statins due to MRSE, fluvastatin XL offers a readily available and effective alternative therapy. Results