在高危患者中，瑞舒伐他汀 10 或 20mg 加依折麦布 10mg 与辛伐他汀 40 或 80mg 加依折麦布 10mg 的疗效、安全性及对胆固醇和脂蛋白代谢相关生物标志物的影响：GRAVITY 随机研究结果。
Efficacy, safety and effect on biomarkers related to cholesterol and lipoprotein metabolism of rosuvastatin 10 or 20 mg plus ezetimibe 10 mg vs. simvastatin 40 or 80 mg plus ezetimibe 10 mg in high-risk patients: Results of the GRAVITY randomized study.
机构信息
Department of Medicine, Baylor College of Medicine and Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston, TX, USA.
Department of Medicine, Baylor College of Medicine and Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston, TX, USA.
出版信息
Atherosclerosis. 2014 Jan;232(1):86-93. doi: 10.1016/j.atherosclerosis.2013.10.022. Epub 2013 Nov 1.
OBJECTIVES
Combination therapy may help high-risk patients achieve low-density lipoprotein cholesterol (LDL-C) goals. Impact of rosuvastatin 10 or 20 mg plus ezetimibe 10 mg (RSV10/EZE10 and RSV20/EZE10) has not been fully characterized previously. GRAVITY (NCT00525824) compared efficacy, safety and effect on biomarkers of RSV10/EZE10 and RSV20/EZE10 vs. simvastatin 40 mg and 80 mg plus EZE10 (SIM40/EZE10 and SIM80/EZE10) in patients with coronary heart disease (CHD) or CHD risk equivalent.
METHODS
Adult patients (n = 833) were randomized to RSV10/EZE10, RSV20/EZE10, SIM40/EZE10 or SIM80/EZE10. Following a 6-week dietary lead-in, patients received 6 weeks' statin monotherapy followed by same statin dose plus ezetimibe for 6 more weeks. Primary endpoint was LDL-C change from baseline to 12 weeks.
RESULTS
Significantly greater (p < 0.05) reductions in LDL-C and other atherogenic lipids were observed with RSV20/EZE10 vs. SIM40/EZE10 and SIM80/EZE10 and with RSV10/EZE10 vs. SIM40/EZE10. A significantly greater proportion of patients achieved LDL-C goals of <100 mg/dl and <70 mg/dl with RSV20/EZE10 vs. SIM40/EZE10 and SIM80/EZE10 and with RSV10/EZE10 vs. SIM40/EZE10. LDL-C was reduced ∼10-14% further with combination therapy vs. monotherapy. Statin monotherapy reduced cholesterol and bile acid synthesis biomarkers, ezetimibe reduced β-sitosterol (sterol absorption marker), and combination therapy achieved additive reductions in lipoprotein-associated phospholipase A2 mass and activity, free cholesterol and 7-ketocholesterol. Safety profiles of rosuvastatin/ezetimibe and simvastatin/ezetimibe combinations were comparable.
CONCLUSION
Co-administration of rosuvastatin 10 or 20 mg plus ezetimibe achieved significant improvements in lipid profiles in high-risk patients vs. simvastatin 40 or 80 mg plus ezetimibe.
目的
联合治疗可能有助于高危患者达到低密度脂蛋白胆固醇（LDL-C）目标。以前尚未充分描述过瑞舒伐他汀 10 或 20mg 加依折麦布 10mg（RSV10/EZE10 和 RSV20/EZE10）的作用。GRAVITY（NCT00525824）比较了瑞舒伐他汀 10/EZE10、瑞舒伐他汀 20/EZE10 与辛伐他汀 40mg 和 80mg 加依折麦布（SIM40/EZE10 和 SIM80/EZE10）在冠心病（CHD）或 CHD 风险等效患者中的疗效、安全性和对生物标志物的影响。
方法
成年患者（n=833）随机分为 RSV10/EZE10、RSV20/EZE10、SIM40/EZE10 或 SIM80/EZE10 组。经过 6 周的饮食导入期后，患者接受 6 周的他汀类药物单药治疗，然后再用相同的他汀类药物加依折麦布治疗 6 周。主要终点是从基线到 12 周时 LDL-C 的变化。
结果
与 SIM40/EZE10 和 SIM80/EZE10 相比，瑞舒伐他汀 20/EZE10 显著降低（p<0.05）LDL-C 和其他致动脉粥样硬化脂质；与 SIM40/EZE10 相比，瑞舒伐他汀 10/EZE10 也显著降低了 LDL-C。与 SIM40/EZE10 和 SIM80/EZE10 相比，瑞舒伐他汀 20/EZE10 组和瑞舒伐他汀 10/EZE10 组有更大比例的患者达到 LDL-C<100mg/dl 和 LDL-C<70mg/dl 的目标。与单药治疗相比，联合治疗使 LDL-C 进一步降低了 10-14%。他汀类药物单药治疗降低了胆固醇和胆汁酸合成生物标志物，依折麦布降低了β-谷固醇（甾醇吸收标志物），联合治疗使脂蛋白相关磷脂酶 A2 质量和活性、游离胆固醇和 7-酮胆固醇的降低具有相加作用。瑞舒伐他汀/依折麦布和辛伐他汀/依折麦布联合治疗的安全性相似。
结论
与辛伐他汀 40 或 80mg 加依折麦布相比，瑞舒伐他汀 10 或 20mg 加依折麦布联合治疗可显著改善高危患者的血脂谱。
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