Efficacy and safety of ezetimibe/simvastatin association on non-diabetic and diabetic patients with polygenic hypercholesterolemia or combined hyperlipidemia and previously intolerant to standard statin treatment.

BACKGROUND AND OBJECTIVE: One of the problems associated with reaching the low-density lipoprotein cholesterol (LDL-C) target during statin treatment is the emergence of laboratory or clinical side effects. The aim of our study was to evaluate the prevalence of statin-associated adverse events in diabetic and non-diabetic patients affected by polygenic hypercholesterolemia or combined hyperlipidemia and the efficacy and tolerability of treatment with ezetimibe/simvastatin 10/10 mg/day on the same subjects experiencing the adverse events.

METHODS: Consecutively enrollment of patients affected by polygenic hypercholesterolemia or combined hyperlipidemia with or without type 2 diabetes mellitus. Each Centre used any of the available statins on the basis of current clinical judgement and monitored enrolled patients for adverse events during the following 2 years. Those patients with moderate adverse events suspended the current statin therapy for 1 month (washout period), and then were shifted to treatment with ezetimibe/simvastatin 10/10 mg/day and again monitored for adverse events in the following 6 months. We assessed body mass index, glycated haemoglobin, fasting plasma glucose, total cholesterol, LDL-C, high-density lipoprotein cholesterol, triglycerides, alanine aminotransferase, aspartate aminotransferase, creatinine phosphokinase and monitored adverse events such as asthenia and myalgia.

RESULTS AND DISCUSSION: All 1170 Caucasian patients affected by polygenic hypercholesterolemia obtained a significant reduction in LDL-C during the observation period (P < 0*05), while those with combined hyperlipidemia also showed a reduction in TG plasma level (P < 0*05) and a significant increase in HDL-C (P < 0*05). Patients affected by polygenic hypercholesterolemia experiencing adverse event under statin treatment obtained a significantly lower reduction than those tolerating the treatment (P < 0*001). The prevalence of adverse events under statin treatment was 4*9% in non-diabetic patients with polygenic hypercholesterolemia, 8*6% in those with combined hyperlipidemia, 7*1% in diabetic patients with polygenic hypercholesterolemia and 7*6% in those with combined hyperlipidemia. Six months after the shift to treatment with ezetimibe/simvastatin 10/10 mg, all patients experienced a significant improvement in LDL-C, TG and HDL-C plasma level. No adverse event was registered during the ezetimibe/simvastatin 10/10 mg treatment period. It seems that previous side effects observed with statins did not re-appear with the administration of ezetimibe/simvastatin 10/10 mg/day.

CONCLUSIONS: The efficacy and adverse effect profile of the ezetimibe and simvastatin combination appear to be good for both diabetic and nondiabetic patients, and in both conditions.