Department of Internal Medicine, University of Ioannina Medical School, Ioannina, Greece.
Eur J Clin Invest. 2013 Jul;43(7):698-707. doi: 10.1111/eci.12095. Epub 2013 Apr 20.
The effects of different hypolipidemic treatment strategies on emerging atherosclerosis risk factors remain unknown.
This is a prespecified analysis of a prospective, randomized, open-label, blinded end point (PROBE) study (ClinicalTrials.gov identifier: NCT01010516). Patients (n = 100) with mixed dyslipidaemia on a standard statin dose who had not achieved lipid targets were randomized to switch to the highest dose of rosuvastatin (40 mg/day) or to add-on-statin extended release nicotinic acid (ER-NA)/laropiprant (LRPT) or to add-on-statin micronized fenofibrate for a total of 3 months.
Following 3 months of treatment, low-density lipoprotein (LDL) particle size increased equally in all groups. Similarly, all treatments were associated with comparable small dense LDL cholesterol reduction. Apolipoprotein B levels decreased by 15%, 7% and 4% in the rosuvastatin, add-on ER-NA/LRPT and add-on fenofibrate group, respectively (P < 0.01 for all compared with baseline, P < 0.01 for all comparisons between groups). Only add-on ER-NA/LRPT was associated with lipoprotein (a) reduction (26%, P < 0.01 compared with baseline). Rosuvastatin monotherapy and add-on ER-NA/LRPT groups were associated with 56% and 24% reduction in high-sensitivity C-reactive protein levels (hsCRP), respectively (P < 0.01 compared with baseline), while add-on fenofibrate was not associated with changes in hsCRP concentration. Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity decreased similarly in both rosuvastatin and add-on fenofibrate groups, while add-on ER-NA/LRPT was associated with a more pronounced Lp-PLA2 activity reduction. ER-NA/LRPT was associated with more side effects compared with rosuvastatin and add-on fenofibrate.
Add-on ER-NA/LRPT followed by switch to the highest dose rosuvastatin were associated with more pronounced beneficial modifications in emerging cardiovascular risk factors compared with add-on fenofibrate in patients with mixed dyslipidaemia.
不同降脂治疗策略对新兴动脉粥样硬化风险因素的影响尚不清楚。
这是一项前瞻性、随机、开放标签、盲终点（PROBE）研究（ClinicalTrials.gov 标识符：NCT01010516）的预设分析。100 名服用标准他汀剂量但血脂目标未达到的混合性血脂异常患者随机分为三组：换用最高剂量的瑞舒伐他汀（40mg/天）、加用他汀类药物缓释烟酸（ER-NA）/拉罗匹仑（LRPT）或加用他汀类药物微粒化非诺贝特，治疗共 3 个月。
治疗 3 个月后，所有组的低密度脂蛋白（LDL）颗粒大小均同等增加。同样，所有治疗均与相当的小而密 LDL 胆固醇降低相关。瑞舒伐他汀组、加用 ER-NA/LRPT 组和加用非诺贝特组的载脂蛋白 B 水平分别下降 15%、7%和 4%（与基线相比均 P < 0.01，组间比较均 P < 0.01）。仅加用 ER-NA/LRPT 与脂蛋白（a）降低相关（降低 26%，与基线相比 P < 0.01）。瑞舒伐他汀单药治疗和加用 ER-NA/LRPT 组的高敏 C 反应蛋白（hsCRP）水平分别降低 56%和 24%（与基线相比均 P < 0.01），而加用非诺贝特组与 hsCRP 浓度无变化。瑞舒伐他汀组和加用非诺贝特组的脂蛋白相关磷脂酶 A2（Lp-PLA2）活性均相似下降，而加用 ER-NA/LRPT 与更明显的 Lp-PLA2 活性降低相关。与瑞舒伐他汀和加用非诺贝特相比，加用 ER-NA/LRPT 相关的副作用更多。
与加用非诺贝特相比，混合性血脂异常患者在换用最高剂量瑞舒伐他汀后加用 ER-NA/LRPT，可使新兴心血管风险因素得到更显著的改善。
