Hoeg J M, Maher M B, Bailey K R, Zech L A, Gregg R E, Sprecher D L, Brewer H B
Am J Cardiol. 1985 May 1;55(11):1282-6. doi: 10.1016/0002-9149(85)90489-8.
Recent prospective clinical trials have established that cholesterol reduction in patients with elevated (upper 90th percentile) concentrations of low-density lipoproteins (LDL) reduces the incidence of myocardial infarction and sudden death. Because the level of protection from these cardiovascular sequelae is directly related to the degree of LDL reduction, combination therapy using different hypolipidemic agents has been used in patients with type II hyperlipoproteinemia (HLP). Neomycin is as effective as cholestyramine in reducing LDL levels and combination neomycin-niacin treatment normalizes the plasma lipoproteins in 92% of patients with type II HLP. Because neomycin could theoretically ameliorate some of the gastrointestinal side effects of cholestyramine in addition to further affecting cholesterol levels, the effects of combination cholestyramine-neomycin treatment on the plasma lipoprotein were assessed in 18 patients with type II HLP in a 9-month clinical trial. Compared with diet-only treatment, cholestyramine reduced total and LDL cholesterol levels by 77 mg/dl (22%) and 78 mg/dl (31%), respectively. In addition to relieving cholestyramine-induced constipation, neomycin further reduced the total cholesterol level by 20 mg/dl (6%). However, this further reduction in total cholesterol concentration was the result of a decrease in the concentration of high-density lipoprotein cholesterol. These findings indicate that combination therapy does not have an additive LDL cholesterol-lowering effect and that neomycin and cholestyramine is not a useful drug combination. In addition, these results illustrate the importance of determining the high-density lipoprotein cholesterol concentration to fully interpret the effects of hypolipidemic treatment.
近期的前瞻性临床试验已证实,降低低密度脂蛋白(LDL)浓度处于升高状态(第90百分位数以上)的患者的胆固醇水平,可降低心肌梗死和猝死的发生率。由于对这些心血管后遗症的保护水平与LDL降低程度直接相关,因此,不同降血脂药物的联合疗法已应用于II型高脂蛋白血症(HLP)患者。新霉素在降低LDL水平方面与消胆胺同样有效,新霉素-烟酸联合治疗可使92%的II型HLP患者的血浆脂蛋白恢复正常。由于新霉素理论上除了能进一步影响胆固醇水平外,还可改善消胆胺的一些胃肠道副作用,因此在一项为期9个月的临床试验中,对18例II型HLP患者评估了消胆胺-新霉素联合治疗对血浆脂蛋白的影响。与单纯饮食治疗相比,消胆胺使总胆固醇和LDL胆固醇水平分别降低了77mg/dl(22%)和78mg/dl(31%)。新霉素除了缓解消胆胺引起的便秘外,还使总胆固醇水平进一步降低了20mg/dl(6%)。然而,总胆固醇浓度的进一步降低是高密度脂蛋白胆固醇浓度下降的结果。这些发现表明,联合治疗没有额外的降低LDL胆固醇的作用,新霉素和消胆胺不是一种有效的药物组合。此外,这些结果说明了在全面解读降血脂治疗效果时测定高密度脂蛋白胆固醇浓度的重要性。