Abstract 12204: Long-Term Effect of Ezetimibe-Plus-Statin vs Double-Dose Statin on Low-Density Lipoprotein Cholesterol Lowering in Coronary Artery Disease Patients Pre-Treated with a Statin; Focus on Cholesterol Absorption and Synthesis
Background: Long-term effect of ezetimibe-plus-statin therapy on low-density lipoprotein cholesterol (LDL-C) lowering including cholesterol metabolism (absorption and synthesis) remains unclear.
Methods: We performed a multi-center, prospective, randomized trial involving 143 coronary artery disease patients whose LDL-C level ≥ 70 mg/dL after treatment with atorvastatin 10 mg/day or rosuvastatin 2.5 mg/day (standard initial dose in Japan). Patients were randomly assigned to receive either ezetimibe 10mg/day plus a statins (E/S: n=74) or a double dose of statin (atorvastatin 20 mg/day or rosuvastatin 5.0 mg/day, D/S: n=69) for 52 weeks. We measured lipid profile including campesterol (as an absorption marker) and lathosterol (as a synthesis marker). In addition, the ratio of cholesterol absorption/synthesis marker (campesterol/lathosterol) was calculated to describe the metabolism of cholesterol.
Results: Baseline patient's characteristics including lipid profile did not differ between the E/S group and the D/S group. From baseline to week 12, the LDL-C level decreased in both the E/S group and the D/S group, and the decrease in LDL-C level was greater in the former (-28±17 mg/dL vs -17±16 mg/dL, p<0.01). The E/S group maintained the LDL-C level after week 12, whereas the D/S group presented an increase in the LDL-C level after week 12; consequently, the difference in LDL-C levels between two groups grew until week 52. The ratio of campesterol/lathosterol level decreased from baseline to week 12 and maintained afterward in the E/S group. In contrast, it showed consistent increase in the D/S group until week 52.
Conclusion: Ezetimibe-plus-statin therapy provided greater LDL-C reduction compared with double-dose statin therapy and kept the balance of cholesterol metabolism through 52 weeks. These results suggest that escape phenomenon, caused by long-term statin monotherapy, can be prevented by an addition of ezetimibe to a statin.
- © 2011 by American Heart Association, Inc.