Efficacy of ezetimibe in patients with statin-resistant and statin-intolerant familial hyperlipidaemias.
OBJECTIVE
To investigate the efficacy of the cholesterol absorption inhibitor ezetimibe in patients with refractory familial hyperlipidaemia or intolerant to statin therapy.


METHODS
This prospective study assessed the safety and efficacy of ezetimibe in 200 patients with refractory familial hyperlipidaemias not achieving a low-density-lipoprotein (LDL) cholesterol < 3 cholesterol < 3 mmol/L (116 mg/dL) including 22% intolerant to all statin therapy, many consuming intolerant to all statin therapy, many consuming sterol-containing products.


RESULTS
Ezetimibe monotherapy resulted in 7% and 11% reductions in LDL-cholesterol and apolipoprotein B respectively. Ezetimibe-statin combination therapy reduced LDL-cholesterol by an additional 11 +/- 27% and apolipoprotein B by 11 (+79 to -18)%. There was a similar response between various sub-groups but a wide variation within groups with the greatest effect seen in patients groups with the greatest effect seen in patients under-responding to statins. The number of patients achieving the LDL-C target of 3 mmol/L rose from 5.5% to 18%. Non-significant effects included a 5 (+78 to -470)% reduction in triglycerides, 8 +/- 36% increment in HDL-cholesterol, 21 (+35 to -82)% reduction in C-reactive protein and a 1 (+20 to -50)% increase in alanine transaminase. No effects were seen on creatinine, creatine kinase, or insulin resistance. Fourteen patients (7%) discontinued ezetimibe: seven due to gastrointestinal side-effects, one patient developed an ezetimibe-induced hypercholesterolaemia (x 1.5), one developed ezetimibe-induced hypertriglyceridaemia (x 7) and five discontinued for other reasons.


CONCLUSIONS
Ezetimibe is a useful addition to statins in patients with familial hyperlipidaemias but shows a highly variable response profile.
Wierzbicki
Anthony S
AS
Department of Chemical Pathology, St. Thomas' Hospital, London, UK. Anthony.Wierzbicki@kcl.ac.uk
Doherty
Emma
E
Lumb
Peter J
PJ
Chik
George
G
Crook
Martin A
MA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001384:Azetidines / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000032:analysis; D008078:Cholesterol, LDL / Q000097:blood; D004351:Drug Resistance; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D006950:Hyperlipidemia, Familial Combined / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002097:C-Reactive Protein; D000069438:Ezetimibe