Hospital Israelita Albert Einstein, Av Albert Einstein, Paulo-SP, Brazil.
J Cardiovasc Pharmacol Ther. 2013 Sep;18(5):447-52. doi: 10.1177/1074248413489771. Epub 2013 Jun 5.
Patients with coronary artery disease (CAD) should be treated with statins to attain very low cholesterol levels, in order to reduce cardiovascular adverse events. More than 70% of these patients do not reach the appropriate cholesterol goal despite moderate statin doses. However, it is not known whether therapeutic uptitration with different lipid-lowering strategies has a similar "pleiotropic" effect on atherosclerotic endothelial dysfunction evaluated by measurement of endothelial progenitor cells (EPCs).
We sought to compare, in patients with stable CAD and with a low-density lipoprotein cholesterol (LDL-C) >70 mg/dL on treatment with simvastatin 20 mg, the effects on EPCs by increasing simvastatin to 80 mg versus adding ezetimibe 10 mg.
Patients (n = 68, 63 ± 9 years, 39% men) were randomly allocated to receive ezetimibe 10/simvastatin 20 mg or simvastatin 80 mg for 6 weeks. Circulating EPCs were measured by flow cytometry before and after the treatment.
Both strategies presented similar effects on metabolic parameters. The LDLs were equally reduced by ezetimibe 10/simvastatin 20 mg and simvastatin 80 mg (28.9% ± 13% vs 21.1% ± 33%; P = .46, respectively). The levels of EPCs were unaffected by ezetimibe 10/simvastatin 20 mg (median [25th, 75th]: pre- vs posttreatment, 7.0 [2.3; 13.3] vs 3.1 [0.1; 13.2] EPCs/10(4) mononuclear cells; P = .43) or simvastatin 80 mg (pre- vs posttreatment, 6.1 [2.9; 15.2] vs 4.0 [1.4; 10.7] EPCs/10(4) mononuclear cells; P = .5), and there were no differences between the groups on treatment effects (P = .9).
Among stable patients with CAD and with an LDL-C >70 mg/dL on simvastatin 20 mg, increasing simvastatin dose to 80 mg or adding ezetimibe 10 mg promoted similar further cholesterol reduction but did not have incremental effects on circulating EPCs. These data suggest that the effects of simvastatin moderate doses on EPCs are not increased by intensive lipid-lowering strategies (clinicaltrials.gov: NCT00474123).
患有冠状动脉疾病（CAD）的患者应服用他汀类药物将胆固醇水平降至非常低的水平，以降低心血管不良事件的风险。尽管使用了中等剂量的他汀类药物，仍有超过 70%的患者无法达到适当的胆固醇目标。然而，目前尚不清楚不同降脂策略的治疗性滴定是否会对动脉粥样硬化内皮功能障碍产生类似的“多效性”影响，这种影响可以通过测量内皮祖细胞（EPCs）来评估。
我们旨在比较在服用辛伐他汀 20mg 治疗、低密度脂蛋白胆固醇（LDL-C）>70mg/dL 的稳定型 CAD 患者中，将辛伐他汀增至 80mg 与加用依折麦布 10mg 对 EPCs 的影响。
将 68 例（63±9 岁，39%为男性）患者随机分为依折麦布/辛伐他汀 20mg 组或辛伐他汀 80mg 组，治疗 6 周。在治疗前后，通过流式细胞术测量循环 EPCs。
两种策略对代谢参数均具有相似的影响。依折麦布/辛伐他汀 20mg 和辛伐他汀 80mg 同样降低 LDL（分别为 28.9%±13%比 21.1%±33%；P=0.46）。依折麦布/辛伐他汀 20mg （中位数[25%，75%]：治疗前vs治疗后，7.0[2.3;13.3] vs 3.1[0.1;13.2]EPCs/10(4)单核细胞；P=0.43）或辛伐他汀 80mg （治疗前 vs治疗后，6.1[2.9;15.2] vs 4.0[1.4;10.7]EPCs/10(4)单核细胞；P=0.5）均未影响 EPCs 水平，且两组间治疗效果无差异（P=0.9）。
在服用辛伐他汀 20mg 的稳定型 CAD 患者中，将辛伐他汀剂量增至 80mg 或加用依折麦布 10mg，可进一步降低胆固醇，但对循环 EPCs 无额外影响。这些数据表明，他汀类药物中等剂量对 EPCs 的影响不会因强化降脂策略而增加（临床试验.gov：NCT00474123）。
