Differential effects of short-term lipid lowering with ezetimibe and statins on endothelial function in patients with CAD:: clinical evidence for 'pleiotropic' functions of statin therapy
Differential effects of short-term lipid lowering with ezetimibe and statins on endothelial function in patients with CAD:: clinical evidence for 'pleiotropic' functions of statin therapy
复制标题
DOI：
10.1093/eurheartj/ehi881
复制
发表时间：
2006-05-01
影响因子：
39.3
通讯作者：
Zeiher, AM
中科院分区：
文献类型：
--
作者：
Fichtlscherer, S;Schmidt-Lucke, C;Zeiher, AM
目的他汀类药物治疗与改善内皮血管舒张功能有关。依折麦布是一种有效的新型胆固醇吸收抑制剂，能够区分降脂作用和潜在的非降脂作用方法和结果前臂血流（FBF）对乙酰胆碱（ACH）和硝普钠（SNP）的反应通过静脉闭塞体积描记术在四个前瞻性定义的稳定性冠状动脉疾病（CAD）患者组中测量。在降脂治疗4周前后。A组（n=15）：依折麦布10 mg/天的初治单药治疗; B组（n=15）：依折麦布10 mg/天作为辛伐他汀20 mg/天长期治疗的添加治疗; C组（n=15）：阿托伐他汀剂量从长期10 mg/天递增至40 mg/天; D组（n=15）：阿托伐他汀40 mg/天的初治单药治疗。治疗4周后，所有四组的LDL胆固醇水平均显著降低。依折麦布单药治疗（A组）或依折麦布与20 mg辛伐他汀联合治疗（B组）均未导致4周后ACH介导的FBF应答增加。相反，阿托伐他汀剂量从10 mg/d增加到40 mg/d（C组）或阿托伐他汀40 mg/d（D组）的重新治疗与ACH介导的FBF反应显著增加相关（P < 0.013）。然而，只有他汀类药物治疗与改善内皮血管舒张功能相关，揭示了他汀类药物在CAD患者短期治疗中的多效性作用的相关性。
Aims Statin therapy is associated with improved endothelial vasodilator function. The clinical availability of ezetimibe, a potent novel cholesterol absorption inhibitor, enables to differentiate lipid-lowering effects from potential non-lipid-lowering (pleiotropic) mechanisms of statins.Methods and results Forearm blood flow (FBF) responses to acetylcholine (ACH) and sodium nitroprusside (SNP) were measured by venous occlusion plethysmography in four prospectively defined groups of patients with stable coronary artery disease (CAD) before and after 4 weeks of lipid-lowering therapy. Group A (n=15): de novo monotherapy with 10 mg/day ezetimibe; Group B (n=15): 10 mg/day ezetimibe as an add-on to chronic simvastatin therapy with 20 mg/day; Group C (n=15): dose escalation from chronic 10 to 40 mg/day atorvastatin; and Group D (n=15): de novo monotherapy with 40 mg/day atorvastatin. After 4 weeks of therapy, LDL cholesterol levels were significantly reduced in all four groups. Neither ezetimibe monotherapy (Group A) nor ezetimibe combined with 20 mg simvastatin (Group B) was associated with an increase in ACH-mediated FBF responses after 4 weeks. In contrast, dose escalation of atorvastatin from 10 to 40 mg/day (Group C) or de novo therapy with 40 mg atorvastatin/day (Group D) was associated with a significant increase in ACH-mediated FBF responses (P < 0.013).Conclusion Thus, both statins and ezetimibe effectively lower LDL-levels within 4 weeks of therapy. However, only statin therapy is associated with improved endothelial vasodilator function, disclosing the relevance of pleiotropic effects of statins during short-term treatment of patients with CAD.