Wiklund O, Angelin B, Bergman M, Berglund L, Bondjers G, Carlsson A, Lindén T, Miettinen T, Odman B, Olofsson S O
Wallenberg Laboratory, Sahlgren's Hospital, Göteborg, Sweden.
Am J Med. 1993 Jan;94(1):13-20. doi: 10.1016/0002-9343(93)90114-5.
To compare the efficacy and safety of pravastatin, gemfibrozil, combined therapy, and placebo in the treatment of hypercholesterolemia.
At 5 centers in Sweden and 2 in Finland, 290 ambulatory patients were randomized to active treatment or placebo for 12 weeks following a single-blind placebo lead-in period. The study was double-blind and placebo-controlled. Patients has plasma total cholesterol levels of at least 6.0 mmol/L or in the 90th percentile by age and sex and triglycerides less than 4.0 mmol/L. Concentrations of lipids, lipoproteins, and apolipoproteins were measured, and clinical laboratory tests included liver function and creatine kinase determinations.
Pravastatin reduced total cholesterol (26.3% versus 15.2%, p < or = 0.01), low-density lipoprotein cholesterol (LDL-C) (33.5% versus 16.8%, p < or = 0.01), and apolipoprotein B (28.8% versus 15.3%, p < or = 0.01) more than gemfibrozil. Gemfibrozil reduced very-low-density lipoprotein cholesterol (VLDL-C) (49.1% versus 21.9%, p < or = 0.01) and triglycerides (42.2% versus 14.2%, p < or = 0.01) and increased high-density lipoprotein cholesterol (HDL-C) (15.2% versus 5.9%, p < or = 0.01) more than pravastatin. Pravastatin and gemfibrozil increased apolipoprotein A-I comparably (3.3% versus 5.0%, p = NS). The combination significantly (p < or = 0.01) reduced total cholesterol (29.0%), LDL-C (37.1%), VLDL-C (49.4%), and apolipoprotein B (31.6%), and increased HDL-C (16.8%). The combination reduced the total cholesterol/HDL-C (39.3%) and LDL-C/HDL-C (45.8%) ratios significantly (p < 0.01). Adverse events and clinical laboratory abnormalities were generally mild and transient in all groups, although creatine kinase tended to be higher with combination therapy. Study drugs were withdrawn from two patients with asymptomatic creatine kinase elevations. Severe myopathy was not observed; however, the presence of subclinical musculoskeletal effects cannot be excluded.
Co-administration of pravastatin and gemfibrozil combined the specific effects of the two drugs on lipoprotein concentrations and ratios. The incidence of side effects was low; severe myopathy did not occur. The combination may be useful in selected cases of combined hyperlipidemia; however, since myopathy at a low incidence or after long-term therapy cannot be excluded, the routine use of combination therapy is not advisable.
比较普伐他汀、吉非贝齐、联合治疗及安慰剂治疗高胆固醇血症的疗效和安全性。
在瑞典的5个中心和芬兰的2个中心，290例门诊患者在单盲安慰剂导入期后，随机接受积极治疗或安慰剂治疗12周。该研究为双盲、安慰剂对照试验。患者的血浆总胆固醇水平至少为6.0 mmol/L，或按年龄和性别处于第90百分位数，甘油三酯低于4.0 mmol/L。测定了脂质、脂蛋白和载脂蛋白的浓度，临床实验室检查包括肝功能和肌酸激酶测定。
普伐他汀降低总胆固醇（分别为26.3%和15.2%，p≤0.01）、低密度脂蛋白胆固醇（LDL-C）（分别为33.5%和16.8%，p≤0.01）和载脂蛋白B（分别为28.8%和15.3%，p≤0.01）的效果优于吉非贝齐。吉非贝齐降低极低密度脂蛋白胆固醇（VLDL-C）（分别为49.1%和21.9%，p≤0.01）和甘油三酯（分别为42.2%和14.2%，p≤0.01）以及升高高密度脂蛋白胆固醇（HDL-C）（分别为15.2%和5.9%，p≤0.01）的效果优于普伐他汀。普伐他汀和吉非贝齐升高载脂蛋白A-I的程度相当（分别为3.3%和5.0%，p=无统计学意义）。联合治疗显著（p≤0.01）降低了总胆固醇（29.0%）、LDL-C（37.1%）、VLDL-C（49.4%）和载脂蛋白B（31.6%），并升高了HDL-C（16.8%）。联合治疗显著降低了总胆固醇/HDL-C（39.3%）和LDL-C/HDL-C（45.8%）比值（p<0.01）。所有组的不良事件和临床实验室异常一般均为轻度且短暂，尽管联合治疗时肌酸激酶往往较高。两名无症状肌酸激酶升高的患者停用了研究药物。未观察到严重肌病；然而，不能排除存在亚临床肌肉骨骼效应。
普伐他汀和吉非贝齐联合使用结合了两种药物对脂蛋白浓度和比值的特定作用。副作用发生率低；未发生严重肌病。联合治疗在某些混合性高脂血症病例中可能有用；然而，由于不能排除低发生率或长期治疗后发生肌病的可能性，不建议常规使用联合治疗。
