Rose H G, Haft G K, Juliano J
Atherosclerosis. 1976 May-Jun;23(3):413-27. doi: 10.1016/0021-9150(76)90003-4.
Plasma lipid and lipoprotein responses to clofibrate were assessed in fifteen hypertriglyceridemic patients for the purpose of ascertaining low-density lipoprotein (LDL) changes. Subjects were grouped into either Type IV (11) or IIB (4) subgroups according to initial LDL level. Clofibrate was without effect on LDL in the IIB group, but consistent, often large, elevations were noted in Type IV cases (mean increase, 37.6%, P less than 0.001). In the IIB subgroup, addition of the bile-acid sequestrant, colestipol, lowered LDL (27.8%, P less 0.02) and total cholesterol (21.3%, P less 0.01) below pre-treatment values. In the Type IV subgroup, LDL fell to 19.5% above baseline (P great than 0.05). Significant LDL elevations induced by clofibrate in three of six subjects were restored to initial levels. In both groups, triglycerides and very-low density lipoproteins (VLDL) were not affected. The efficacy of colestipol in reducing LDL levels, expressed as either absolute or percentage reductions, increased as a function of increasing post-clofibrate LDL concentration (r = 0.84, P less than 0.001). In these subjects the level of LDL after treatment with clofibrate depended upon their LDL level prior to drug therapy, the effect of clofibrate on this level, and lipoprotein phenotype. Thus colestipol was most effective in IIB subjects, Type IV subjects with the lowest baseline VLDL and hence reciprocally highest LDL, and Type IV individuals who exhibited the largest LDL induction by clofibrate. The reported ineffectiveness of clofibrate on mortality and morbidity in patients with established coronary heart disease might be related to elevations and infrequent reductions of LDL. From the perspective of lipoprotein lowering, the combination with colestipol appears more favorable.
为确定低密度脂蛋白（LDL）的变化，对15名高甘油三酯血症患者的血浆脂质和脂蛋白对氯贝丁酯的反应进行了评估。根据初始LDL水平，将受试者分为IV型（11例）或IIB型（4例）亚组。氯贝丁酯对IIB组的LDL无影响，但在IV型病例中观察到LDL持续且通常大幅升高（平均升高37.6%，P<0.001）。在IIB亚组中，添加胆汁酸螯合剂考来替泊可使LDL（降低27.8%，P<0.02）和总胆固醇（降低21.3%，P<0.01）降至治疗前水平以下。在IV型亚组中，LDL降至比基线高19.5%（P>0.05）。氯贝丁酯在6名受试者中引起的3例显著LDL升高恢复到初始水平。在两组中，甘油三酯和极低密度脂蛋白（VLDL）均未受影响。考来替泊降低LDL水平的疗效，无论是以绝对降低值还是百分比降低值表示，均随着氯贝丁酯治疗后LDL浓度的增加而增加（r=0.84，P<0.001）。在这些受试者中，氯贝丁酯治疗后的LDL水平取决于药物治疗前的LDL水平、氯贝丁酯对该水平的影响以及脂蛋白表型。因此，考来替泊在IIB型受试者、基线VLDL最低因而LDL相应最高的IV型受试者以及氯贝丁酯诱导LDL升高幅度最大的IV型个体中最为有效。氯贝丁酯对已确诊冠心病患者的死亡率和发病率无效的报道可能与LDL升高以及LDL很少降低有关。从降低脂蛋白的角度来看，与考来替泊联合使用似乎更有利。
