Maciejko J J, Brazg R, Shah A, Patil S, Rubenfire M
Department of Medicine, Sinai Hospital, Detroit, Mich.
Arch Fam Med. 1994 Nov;3(11):955-60. doi: 10.1001/archfami.3.11.955.
To determine if the bulk-forming laxative, psyllium hydrophilic mucilloid (PHM), reduces the gastrointestinal side effects and enhances the cholesterol-lowering efficacy of cholestyramine resin in patients with primary hypercholesterolemia.
After a dietary lead-in period and 6 weeks of treatment with cholestyramine, the study followed a double-blinded, placebo-controlled, crossover format.
Lipid clinic affiliated with a large metropolitan community hospital.
Twenty-seven randomly selected male and female patients with a diagnosis of primary hypercholesterolemia. Entry criteria required a fasting low-density lipoprotein cholesterol (LDL-C) concentration of 4.91 mmol/L (190 mg/dL) or greater and a triglyceride concentration of less than 2.26 mmol/L. Patients using steroids, beta-blockers, thiazide diuretics, and lipid-lowering agents, or having a history of allergy to psyllium or aspartame were excluded.
The study consisted of four interventional phases of 6 weeks' duration that included (1) dietary stabilization (National Cholesterol Education Program Step I Diet); (2) cholestyramine therapy (4 g twice daily); (3) cholestyramine with study medication (PHM [5.1 g twice daily] or placebo); and (4) cholestyramine with crossover to alternate study medication.
Following the 6-week dietary lead-in phase, four patients were eliminated from the study because their fasting LDL-C concentrations fell below 4.14 mmol/L (160 mg/dL), and one patient was eliminated because testosterone therapy was initiated by his internist. The remaining 22 patients entered the cholestyramine treatment phase. Four left the study within 2 weeks because of intolerable gastrointestinal tract symptoms. The 18 patients who completed this phase demonstrated significant reductions in their plasma total cholesterol (7.27 vs 6.67 mmol/L [281 vs 258 mg/dL]) and LDL-C (5.38 vs 4.63 mmol/L [208 vs 179 mg/dL]) concentrations compared with baseline levels. The addition of PHM to the cholestyramine regimen provided a tendency toward further reductions in total cholesterol and LDL-C levels (6.67 vs 6.46 mmol/L [258 vs 250 mg/dL] and 4.63 vs 4.29 mmol/L [179 vs 166 mg/dL], respectively), although statistical significance was not achieved. Psyllium hydrophilic mucilloid significantly reduced the frequency and severity of constipation, abdominal discomfort, and heartburn. No reports of new gastrointestinal tract symptoms or untoward effects were noted with the addition of PHM.
These data suggest that the addition of PHM to cholestyramine therapy may improve a patient's compliance by reducing the associated gastrointestinal tract side effects.
确定容积性泻药车前草亲水粘胶（PHM）是否能减轻原发性高胆固醇血症患者使用考来烯胺树脂时的胃肠道副作用，并增强其降胆固醇疗效。
在经过饮食导入期和考来烯胺治疗6周后，该研究采用双盲、安慰剂对照、交叉设计。
一家大型都市社区医院附属的脂质门诊。
27名随机选取的诊断为原发性高胆固醇血症的男性和女性患者。入选标准要求空腹低密度脂蛋白胆固醇（LDL-C）浓度为4.91 mmol/L（190 mg/dL）或更高，甘油三酯浓度低于2.26 mmol/L。排除正在使用类固醇、β受体阻滞剂、噻嗪类利尿剂和降脂药物的患者，以及有对车前草或阿斯巴甜过敏史的患者。
该研究包括四个为期6周的干预阶段，包括（1）饮食稳定期（国家胆固醇教育计划第一步饮食）；（2）考来烯胺治疗（每日两次，每次4 g）；（3）考来烯胺加研究药物（PHM[每日两次，每次5.1 g]或安慰剂）；（4）考来烯胺加交叉使用替代研究药物。
在为期6周的饮食导入期后，4名患者因空腹LDL-C浓度降至4.14 mmol/L（160 mg/dL）以下而退出研究，1名患者因内科医生开始给予睾酮治疗而退出。其余22名患者进入考来烯胺治疗阶段。4名患者因无法忍受的胃肠道症状在2周内退出研究。完成该阶段的18名患者与基线水平相比，血浆总胆固醇（7.27 vs 6.67 mmol/L[281 vs 258 mg/dL]）和LDL-C（5.38 vs 4.63 mmol/L[208 vs 179 mg/dL]）浓度显著降低。考来烯胺治疗方案中添加PHM有使总胆固醇和LDL-C水平进一步降低的趋势（分别为6.67 vs 6.46 mmol/L[258 vs 250 mg/dL]和4.63 vs 4.29 mmol/L[179 vs 166 mg/dL]），尽管未达到统计学显著性。车前草亲水粘胶显著降低了便秘、腹部不适和烧心的频率和严重程度。添加PHM后未发现新的胃肠道症状或不良影响的报告。
这些数据表明，考来烯胺治疗中添加PHM可能通过减轻相关胃肠道副作用来提高患者的依从性。
