Miller P Elliott, Martin Seth S, Joshi Parag H, Jones Steven R, Massaro Joseph M, D'Agostino Ralph B, Sponseller Craig A, Toth Peter P
Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland.
Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland.
Clin Ther. 2016 Mar;38(3):603-9. doi: 10.1016/j.clinthera.2016.02.001. Epub 2016 Feb 26.
Remnants are partially hydrolyzed, triglyceride-rich lipoproteins that are implicated in atherosclerosis. We assessed the adequacy of pitavastatin 4 mg and pravastatin 40 mg in reducing atherogenic lipid parameters beyond LDL-C, in particular remnant lipoprotein cholesterol (RLP-C).
From the Phase IV, multicenter, randomized, double-blind PREVAIL US (A Study of Pitavastatin 4 mg Vs. Pravastatin 40 mg in Patients With Primary Hyperlipidemia or Mixed Dyslipidemia) trial, we examined lipoprotein cholesterol subfractions using Vertical Auto Profile testing and apolipoproteins B and A-I at baseline and 12 weeks. Participants with primary hyperlipidemia or mixed dyslipidemia had LDL-C levels of 130 to 220 mg/dL and triglyceride levels ≤ 400 mg/dL. In this post hoc analysis, changes in lipid parameters were compared by using ANCOVA.
Lipoprotein subfraction data were available in 312 patients (pitavastatin, n = 157; pravastatin, n = 155). Pitavastatin promoted a greater reduction in RLP-C than pravastatin (-13.6 [8.7] vs -9.3 [9.5] mg/dL). Furthermore, the pitavastatin group reported greater reductions in both components of RLP-C (both, P < 0.001): intermediate-density lipoprotein cholesterol (-9.5 [6.3] vs -6.4 [6.6] mg/dL) and very low-density lipoprotein cholesterol subfraction 3 (-4.1 [3.5] vs -2.9 [3.8] mg/dL). There were also greater reductions in the major ratios of risk (apolipoprotein B/apolipoprotein A-I and total cholesterol/HDL-C) (both, P < 0.001). There were no significant changes in HDL-C, its subfractions, or natural log lipoprotein(a)-cholesterol. The mean age was 58.8 ± 8.9 years in the pitavastatin group and 57.0 ± 10.2 years in the pravastatin group.
Compared with pravastatin 40 mg daily, pitavastatin 4 mg provided superior reductions in atherogenic lipid parameters beyond LDL-C, including RLP-C. Future studies are needed investigate the clinical implications of lowering directly measured RLP-C as the principal target. ClinicalTrials.gov identifier: NCT01256476.
残余颗粒是部分水解的、富含甘油三酯的脂蛋白，与动脉粥样硬化有关。我们评估了4毫克匹伐他汀和40毫克普伐他汀在降低除低密度脂蛋白胆固醇（LDL-C）之外的致动脉粥样硬化血脂参数方面的充分性，尤其是残余脂蛋白胆固醇（RLP-C）。
从IV期多中心随机双盲的美国PREVAIL试验（一项比较4毫克匹伐他汀与40毫克普伐他汀治疗原发性高脂血症或混合性血脂异常患者的研究）中，我们在基线和12周时使用垂直自动分析测试检查脂蛋白胆固醇亚组分以及载脂蛋白B和A-I。原发性高脂血症或混合性血脂异常患者的LDL-C水平为130至220毫克/分升，甘油三酯水平≤400毫克/分升。在这项事后分析中，使用协方差分析比较血脂参数的变化。
312例患者（匹伐他汀组，n = 157；普伐他汀组，n = 155）有脂蛋白亚组分数据。匹伐他汀比普伐他汀更能降低RLP-C（-13.6 [8.7] 对比 -9.3 [9.5] 毫克/分升）。此外，匹伐他汀组在RLP-C的两个组分上降低幅度更大（均P < 0.001）：中密度脂蛋白胆固醇（-9.5 [6.3] 对比 -6.4 [6.6] 毫克/分升）和极低密度脂蛋白胆固醇亚组分3（-4.1 [3.5] 对比 -2.9 [3.8] 毫克/分升）。主要风险比值（载脂蛋白B/载脂蛋白A-I和总胆固醇/高密度脂蛋白胆固醇）也有更大幅度降低（均P < 0.001）。高密度脂蛋白胆固醇及其亚组分或脂蛋白(a) - 胆固醇的自然对数无显著变化。匹伐他汀组的平均年龄为58.8 ± 8.9岁，普伐他汀组为57.0 ± 10.2岁。
与每日40毫克普伐他汀相比，4毫克匹伐他汀在降低除LDL-C之外的致动脉粥样硬化血脂参数方面表现更优，包括RLP-C。未来需要研究将直接测量的RLP-C作为主要靶点降低的临床意义。ClinicalTrials.gov标识符：NCT01256476。
