血脂康与血脂康联合依折麦布治疗血脂异常的效果比较

Comparison of Xuezhikang monotherapy with Xuezhikang combined with ezetimibe therapy for dyslipidemia

目的评价血脂康联合依折麦布治疗血脂异常的疗效和安全性。方法 2015年9月—2017年12月间从国内7家医院中共筛选196例血脂异常患者,其中63例符合纳入标准,随机分为单药治疗组(31例)和联合治疗组(32例)。单药治疗组给予血脂康0.6 g/次,每日2次。联合治疗组给予血脂康0.6 g/次,每日2次;依折麦布片10 mg,每日1次。随访时间均为8周。于治疗第8周末时检测血清低密度脂蛋白胆固醇(LDL-C)、血清总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、三酰甘油(TG)、非HDL-C、载脂蛋白A1(Apo A1)、血清载脂蛋白B(Apo B)和脂蛋白a[LP(a)]水平及其相对基线水平的变化幅度。记录两组LDL-C水平<2.59 mmol/L患者、<1.8 mmol/L和LDL-C降幅>50%患者的比例。观察两组治疗期间不良事件和严重不良事件发生情况。结果联合治疗组全分析集(FAS)为28例,安全数据集(SS)为32例;单药组FAS为29例,SS为30例。两组间患者的年龄、BMI、血压、吸烟史、糖化血红蛋白水平,以及各项血脂指标基线水平的差异均无统计学意义(P值均>0.05)。治疗第8周末,联合治疗组LDL-C、TC、非HDL-C水平均显著低于单药治疗组(P值均<0.01),其下降幅度均高于单药治疗组(P值均<0.01);HDL-C水平及其变化幅度均显著高于单药治疗组(P值均<0.05)。两组间TG、Apo A1、Apo B、LP(a)水平及其升高幅度的差异均无统计学意义(P值均>0.05)。联合治疗组LDL-C<1.8 mmol/L或LDL-C降幅>50%患者的比例均显著高于单药治疗组(P值均<0.01),两组间LDL-C<2.59 mmol/L患者比例的差异无统计学意义(P>0.05)。联合治疗组、单药治疗组不良事件发生率分别为31.3%(10/32)、40.0%(12/30),两组间差异无统计学意义(P>0.05)。联合治疗组有1例患者肝功能异常的发生无法判断是否与研究药物有关,1例患者轻度胃肠道反应的发生可能与研究药物有关,其余不良事件的发生与研究药物无关;单药治疗组不良事件的发生与研究药物均无关。结论血脂康联合依折麦布治疗可显著降低LDL-C水平,改善TG和HDL-C水平,且安全性良好。

Objective To evaluate the efficacy and safety of Xuezhikang combined with ezetimibe therapy on dyslipidemia. Methods A total of 196 subjects were screened from September 2015 to December 2017 in seven hospitals. Of them, 63 patients were successfully enrolled and randomized to monotherapy group(n=31) and combination therapy group(n=32). Xuezhikang was orally given 0.6 g twice a day in both groups. Ezetimibe was taken additionally(10 mg once daily) in combination therapy group. Serum levels of low density lipoprotein cholesterol(LDL-C), total cholesterol(TC), high density lipoprotein cholesterol(HDL-C), triacylglycerol(TG), non-high density lipoprotein cholesterol(non-HDL-C), apolipoprotein A1(Apo A1), apolipoprotein B(Apo B), lipoprotein a [LP(a)] were measured at 8 weeks after treatment, and their changes were assessed. The proportion of patients with LDL-C<2.59 mmol/L, LDL-C<1.8 mmol/L or a relative reduction>50% were recorded in the two groups. Adverse events and severe adverse events were documented. Results In the combination therapy group, there were 28 subjects in the full analysis set(FAS) and 32 in the safety set(SS). In the monotherapy group, there were 29 subjects in the FAS and 30 in the SS. There were no significant differences in terms of the age, body mass index(BMI), blood pressure, smoking history, glycosylated hemoglobin, or baseline serum lipid indices between the two groups(all P>0.05). Eight weeks after treatment, serum levels of LDL-C, TC and non-HDL-C were significantly lower in the combination therapy group than those in the monotherapy group with greater relative reduction(all P<0.01);while HDL-C level was significantly higher in the combination therapy group compared with monotherapy group with greater relative increase(both P<0.05). There were no significant differences in the TG, Apo A1, Apo B, LP(a) levels or their relative changes between the two groups(all P>0.05). The proportion of patients with LDL-C<1.8 mmol/L or a relative reduction>50% was significantly higher in the combination therapy group than that in the monotherapy group(both P<0.01), whereas the proportion of patients with LDL-C <2.59 mmol/L showed no significant difference between the two groups(P>0.05). Incidence of adverse events was 31.3%(10/32) in the combination therapy group and 40.0%(12/30) in the monotherapy group(P>0.05). In the combination therapy group, one patient showed abnormal hepatic function, but it was hard to judge its relationship with medications;another case developed mild gastrointestinal discomfort, which might be related to medications;other adverse events had nothing to do with medications. In the monotherapy group, none of the adverse events were related to medications.Conclusion Xuezhikang combined with ezetimibe therapy can significantly decrease LDL-C level, and improve TG and HDL-C levels with good safety.