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.
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.


CONCLUSIONS
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.
Derosa
Giuseppe
G
Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy. giuseppe.derosa@unipv.it
D'Angelo
A
A
Franzetti
I G
IG
Ragonesi
P D
PD
Gadaleta
G
G
Scalise
F
F
Ciccarelli
L
L
Piccinni
M N
MN
Cicero
A F G
AF
D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001384:Azetidines / Q000009:adverse effects / Q000627:therapeutic use*; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004338:Drug Combinations; D000069499:Ezetimibe, Simvastatin Drug Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D019821:Simvastatin / Q000009:adverse effects / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D001384:Azetidines; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004338:Drug Combinations; D000069499:Ezetimibe, Simvastatin Drug Combination; D014280:Triglycerides; D019821:Simvastatin