Efficacy and safety of high-dose pravastatin in hypercholesterolemic patients with well-compensated chronic liver disease: Results of a prospective, randomized, double-blind, placebo-controlled, Multicenter trial
Efficacy and safety of high-dose pravastatin in hypercholesterolemic patients with well-compensated chronic liver disease: Results of a prospective, randomized, double-blind, placebo-controlled, Multicenter trial
复制标题
DOI：
10.1002/hep.21848
复制
发表时间：
2007-11-01
期刊：
影响因子：
13.5
通讯作者：
Belder, Rene
中科院分区：
文献类型：
--
作者：
Lewis, James H.;Mortensen, Mary Eflen;Belder, Rene
3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂在基础慢性肝病患者中的肝毒性潜力仍存在争议。我们进行了一项多中心，随机，双盲，安慰剂对照，一项在年龄大于18岁、有至少6个月代偿性慢性肝病史、低密度脂蛋白胆固醇（LDL-C）水平≥ 100 mg/dL和甘油三酯（TG）水平≥ 100 mg/dL的高胆固醇血症受试者中比较普伐他汀（80 mg）与安慰剂每日一次给药的平行组试验低于400 mg/dL。通过LDL-C [沿着总胆固醇（TC）、高密度脂蛋白胆固醇和TG]从基线至第12周的百分比变化确定疗效。根据在36周治疗期间至少发生1次丙氨酸氨基转移酶（ALT）值大于或等于基线时AILT正常的受试者的正常上限的2倍或基线时ALT升高的受试者的基线ALT加倍的受试者比例分析安全性。共筛选了630例受试者，随机分配了326例受试者; 64%存在非酒精性脂肪肝，23%存在慢性丙型肝炎。在意向治疗人群中，与安慰剂相比，普伐他汀（80 mg/天）在第12周和其他时间（第4、8、24和36周）显著降低了平均LDL-C、TC和TG值。在36周治疗期间，普伐他汀组中符合主要预先规定的ALT事件定义的受试者发生率始终低于安慰剂组，尽管差异无统计学显著性。基于基线ALT值或不同肝病组之间未观察到差异。结论高剂量普伐他汀（80 mg/天）治疗慢性肝病高胆固醇血症患者，与安慰剂相比，可显著降低LDL-C、TC和TG，且安全且耐受。基于这些结果，对慢性肝病患者中他汀类药物诱导肝毒性可能性增加的担忧似乎有所减轻。
The hepatotoxic potential of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in patients with underlying chronic liver disease remains controversial. We performed a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial that compared pravastatin (80 mg) to a placebo administered once daily to hypercholesterolemic subjects greater than 18 years of age with at least a 6-month history of compensated chronic liver disease and with a low-density lipoprotein cholesterol (LDL-C) level greater than or equal to 100 mg/dL and a triglyceride (TG) level lower than 400 mg/dL. The efficacy was determined by the percentage change in LDL-C [along with the total cholesterol (TC), high-density lipoprotein cholesterol, and TG] from the baseline to week 12. The safety was analyzed by the proportion of subjects who developed at least 1 alanine aminotransferase (ALT) value greater than or equal to 2 times the upper limit of normal for those with normal AILT at the baseline or a doubling of the baseline ALT for those with elevated ALT at the baseline during 36 weeks of treatment. A total of 630 subjects were screened, and 326 subjects were randomized; nonalcoholic fatty liver disease was present in 64%, and chronic hepatitis C was present in 23%. In the intent-to-treat population, pravastatin (80 mg/day) significantly lowered the mean LDL-C, TC, and TG values at week 12 and at other times (weeks 4, 8, 24, and 36) in comparison with the placebo. The incidence of subjects who met the primary prespecified ALT event definition was lower in the pravastatin group at all times over the 36 weeks of therapy in comparison with the placebo group, although the difference was not statistically significant. No differences were seen on the basis of the baseline ALT values or among the different liver disease groups. Conclusion. High-dose pravastatin (80 mg/day) administered to hypercholesterolemic subjects with chronic liver disease significantly lowered LDL-C, TC, and TGs in comparison with the placebo and was safe and wen tolerated. The concern over an increased potential for statin-induced hepatotoxicity in patients with chronic liver disease appears to be lessened on the basis of these results.