Effects of ezetimibe on lipids and lipoproteins in patients with hypercholesterolemia and different apolipoprotein E genotypes.

BACKGROUND: The epsilon4 allele of the gene encoding apolipoprotein E (apoE) is associated with elevated serum levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), as well as an increased risk of coronary heart disease (CHD), greater disease severity, and higher CHD mortality. ApoE epsilon4 allele carriers have also shown reduced lipid and lipoprotein responses to lipid-modifying pharmacotherapy and lifestyle modifications. OBJECTIVE: To provide preliminary descriptive data on the effects of apoE genotype on lipid and lipoprotein responses to the cholesterol absorption inhibitor ezetimibe (Ezetrol/Zetia) in Hungarian subjects not at cholesterol goals at baseline. METHODS: This prospective open-label study compared the effects of the cholesterol absorption inhibitor ezetimibe 10 mg/day for up to 6 weeks added to existing therapies on the lipid profiles of 14 epsilon4 allele carriers and 14 age- and gender-matched APOE3/APOE3 homozygotes. RESULTS: Treatment with ezetimibe reduced TC, LDL-, and triglycerides, and increased high-density lipoprotein cholesterol (HDL-) significantly from baseline, and to similar extents, in both groups, lowering TC from baseline by 13.7% in APOE3/APOE3 homozygotes compared with 12.1% in epsilon4 allele carriers (p = 0.139); LDL-C by 22.8% (vs. 19.6%; p = 0.081); and triglycerides by 9.2% (vs. 9.1%; p = 0.120). Ezetimibe also increased HDL-C by 8.0% in subjects with the epsilon3/epsilon3 genotype compared with 8.9% in epsilon4 allele carriers (p = 0.263). CONCLUSIONS: Ezetimibe significantly improved lipid and lipoprotein profiles from baseline irrespective of apoE epsilon3/epsilon3 or epsilon4 genotype in Hungarian subjects not at cholesterol goals. Limitations of our study include its open-label nature and small sample population, as well as the facts that patients with the epsilon4 allele were not included and data were not collected on initial cholesterol levels, initial statin doses, cholesterol responses to statins, and the safety and tolerability of ezetimibe. Further randomized controlled studies in larger numbers of people followed for longer intervals are warranted to confirm these findings.