Insull W, Davidson M H, Demke D M, Dujovne C A, Eckert S M, Ginsberg D, Goldberg A C, Hodis H N, Hughes T A, Kane J P
Lipid Research Clinic, Baylor College of Medicine, Methodist Hospital, Houston, TX 77030, USA.
Atherosclerosis. 1995 Jan 20;112(2):223-35. doi: 10.1016/0021-9150(94)05418-i.
The purpose of this study was to investigate and compare the efficacy, safety, and patient acceptability of a new formulation of colestipol, colestipol tablets (T), with those of colestipol granules (G), in a randomized, double-blind, placebo-controlled, multicenter study. Three hundred and seventeen patients with primary hypercholesterolemia who were following a low-fat, low-cholesterol diet (NCEP Step I diet), and had low-density lipoprotein cholesterol (LDL-C) levels > or = 4.14 mmol/l (160 mg/dl) and < or = 6.46 mmol/l (250 mg/dl) were studied. Study medication was taken twice a day, with breakfast and supper, for 8 weeks. The six parallel treatment groups consisted of colestipol tablets 2 g b.i.d. and 8 g b.i.d., matching placebo tablets b.i.d., colestipol granules 2 g b.i.d. and 8 g b.i.d., and matching placebo granules b.i.d.. Study endpoints included absolute change and percentage change from baseline in selected lipid, lipoprotein, and apolipoprotein measurements; LDL-C lowering was the primary efficacy endpoint. Treatment with colestipol tablets and colestipol granules resulted in virtually identical, statistically significant (P < or = 0.05) reductions of LDL-C, total cholesterol (TC), TC/HDL-C, and apolipoprotein B (apo B). Compared with placebo, all active treatments (tablets 4 g/day, tablets 16 g/day, granules 4 g/day, granules 16 g/day) significantly reduced LDL-C (12%, 24%, 12%, 25%, respectively), TC (7%, 15%, 8%, 15%, respectively), TC/HDL-C (8%, 14%, 9%, 15%, respectively) and apo B (12%, 20%, 13%, 22%, respectively). All active treatments significantly increased lipoprotein particle AI (LpAI) (5%, 23%, 14%, 18%, respectively). VLDL-C and triglycerides increased significantly in the high-dose groups. The proportions of patients reporting adverse events, largely gastrointestinal-related, were not different among the active treatment groups. The treatments were well-tolerated, and no drug-related serious adverse events were reported. Patients experienced with granule medication prior to this study preferred tablets over granules. This study demonstrates that colestipol tablets are an effective treatment to reduce LDL-C in patients with primary hypercholesterolemia, are equivalent to colestipol granules, are well-tolerated, and are preferred over granules by patients.
本研究旨在通过一项随机、双盲、安慰剂对照、多中心研究，调查并比较考来替泊新制剂考来替泊片（T）与考来替泊颗粒（G）的疗效、安全性及患者可接受性。对317例原发性高胆固醇血症患者进行了研究，这些患者遵循低脂、低胆固醇饮食（NCEP第一步饮食），低密度脂蛋白胆固醇（LDL-C）水平≥4.14 mmol/l（160 mg/dl）且≤6.46 mmol/l（250 mg/dl）。研究药物每日服用两次，与早餐和晚餐同服，共服用8周。六个平行治疗组分别为：考来替泊片2 g，每日两次；考来替泊片8 g，每日两次；匹配的安慰剂片，每日两次；考来替泊颗粒2 g，每日两次；考来替泊颗粒8 g，每日两次；匹配的安慰剂颗粒，每日两次。研究终点包括选定的脂质、脂蛋白和载脂蛋白测量值相对于基线的绝对变化和百分比变化；降低LDL-C是主要疗效终点。考来替泊片和考来替泊颗粒治疗导致LDL-C、总胆固醇（TC）、TC/HDL-C和载脂蛋白B（apo B）的降低在统计学上几乎相同且具有显著性（P≤0.05）。与安慰剂相比，所有活性治疗（片剂4 g/天、片剂16 g/天、颗粒剂4 g/天、颗粒剂16 g/天）均显著降低了LDL-C（分别为12%、24%、12%、25%）、TC（分别为7%、15%、8%、15%）、TC/HDL-C（分别为8%、14%、9%、15%）和apo B（分别为12%、20%、13%、22%）。所有活性治疗均显著增加了脂蛋白颗粒AI（LpAI）（分别为5%、23%、14%、18%）。高剂量组的极低密度脂蛋白胆固醇（VLDL-C）和甘油三酯显著升高。各活性治疗组中报告不良事件（主要与胃肠道相关）的患者比例无差异。这些治疗耐受性良好，未报告与药物相关的严重不良事件。在本研究之前使用颗粒剂药物的患者更喜欢片剂而非颗粒剂。本研究表明，考来替泊片是降低原发性高胆固醇血症患者LDL-C的有效治疗方法，与考来替泊颗粒等效，耐受性良好，且患者更喜欢片剂而非颗粒剂。
