Efficacy and safety of ezetimibe coadministered with pravastatin in patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial.

AIMS: To evaluate the efficacy and safety of ezetimibe 10 mg administered with pravastatin in patients with primary hypercholesterolemia. METHODS AND RESULTS: After dietary stabilization, 2-12 week screening/washout period, and 4-week, single-blind, placebo lead-in period, 538 patients with baseline LDL-C > or =3.8 to < or =6.5 mmol/l and TG < or =4.0 mmol/l were randomized to one of eight possible treatments administered daily for 12 weeks: ezetimibe 10mg; pravastatin 10, 20, or 40 mg; ezetimibe 10 mg plus pravastatin 10, 20, or 40 mg; or placebo. The primary efficacy endpoint was percent reduction in LDL-C from baseline to study endpoint for ezetimibe 10 mg plus pravastatin (pooled doses) compared to pravastatin alone (pooled doses) and ezetimibe alone. The combined use of ezetimibe and pravastatin resulted in significant incremental reductions in LDL-C and TG compared to pooled pravastatin alone (p<0.01). Coadministration therapy reduced LDL-C by 34-41%, TG by 21-23%, and increased HDL-C by 7.8-8.4%, depending on the dose of pravastatin. The combined regimen was well tolerated, with a safety profile similar to pravastatin alone and placebo. CONCLUSIONS: When coadministered with pravastatin, ezetimibe provided significant incremental reductions in LDL-C and TG and was well tolerated with a safety profile similar to pravastatin alone.     

阿托伐他汀联合依折麦布治疗急性冠脉综合征的临床效果分析

目的 研究阿托伐他汀联合依折麦布在治疗急性冠脉综合征(ACS)中的临床应用效果.方法 将本院在2012年1月至2015年12月期间收治的60例ACS患者分成对照组和联合治疗组,每组各30例,对照组患者给予口服阿托伐他汀,联合治疗组在对照组基础上加服依折麦布.比较两组的治疗效果.结果 ①与治疗前比较,两组血清TC、TG、LDL-C和hs-CRP均明显下降(P＜0.05),而联合治疗组下降幅度显著大于对照组(P＜0.05);治疗前后两组血清HDL-C水平无明显变化(P＞0.05);②治疗后,联合治疗组再发心绞痛和心肌梗死率显著低于对照组(P＜0.05).结论 阿托伐他汀联合依折麦布能够明显改善ACS患者血脂状况,减少心血管事件.     

依折麦布联合阿托伐他汀治疗冠心病

目的：评价依折麦布联合阿托伐他汀对常规剂量他汀药物血脂控制不佳的冠心病患者的疗效。方法：选择服用常规剂量他汀药物血脂控制不佳的冠心病患者126例,随机分为依折麦布联合他汀药物治疗组62例（依折麦布10mg／d＋阿托伐他汀10mg／d）和双倍剂量他汀药物治疗组64例（阿托伐他汀20mg／d）。持续24周测定两组患者的总胆固醇（TC）,LDL-C,高密度脂蛋白胆固醇（HDL-C）,菜油甾醇/7-烯胆甾烷醇和血浆前蛋白转化酶枯草溶菌素9（PSCK9）的含量的变化。结果：联合依折麦布治疗组LDL-C水平,菜油甾醇/7-烯胆甾烷醇比例和PSCK9水平明显低于双倍剂量阿托伐他汀治疗组。双倍剂量阿托伐他汀治疗组LDL-C水平在12周后逐渐回升而联合依折麦布治疗组LDL-C水平降低较为平稳。结论：对常规他汀剂量血脂控制不佳的患者联合依折麦布能有效抑制胆固醇的吸收和合成并且降低LDL-C效果明显优于单纯加大他汀药物剂量。     

HPLC测定(S)-4-苯基-2-噁唑烷酮的纯度

目的采用HPLC法测定(S)-4-苯基-2-噁唑烷酮(SPO)的纯度。方法采用Welchrom C18色谱柱,流动相为0.02 mol·L-1磷酸二氢钾(KOH调p H5)-乙腈(60∶40),检测波长210 nm,流速1.0 m L·min-1,柱温35℃。结果 SPO0.3036~6.072μg·m L-1与峰面积的线性关系良好(r=0.9999),检测限和定量限分别为0.9099、3.033 ng。结论所用方法准确、灵敏、快速,适用于检测SPO中的微量杂质。     

Lifestyle versus ezetimibe plus lifestyle in patients with biopsy-proven non-alcoholic steatohepatitis (LISTEN): A double-blind randomised placebo-controlled trial

Background and aimsThe LISTEN trial (ClinicalTrial.gov accession: NCT01950884) is a phase IV 52 weeks double blind parallel randomized controlled trial that evaluated the effect of ezetimibe plus lifestyle and dietary intervention (eze) vs. lifestyle and dietary intervention alone (placebo) on progression and complications of non-alcoholic steatohepatitis (NASH) evaluated by liver histology.Methods and resultsForty patients with NASH ascertained by histology were randomly allocated on the two study groups and subjected to a follow-up of 52 weeks, when they underwent a second liver biopsy. Main composite end point (EP) was based on the histological improvement in the severity of NASH.Thirty patients completed the study, Eze treatment was not able to improve the primary EP in comparison with placebo, with and odds ratio of 1.029 (0.18–6.38), p = 0.974. Treatment emergent adverse events registered during the study were not more prevalent in the treatment arm.Conclusionsezetimibe administered on top of lifestyle and dietary modification failed to improve the histology of NASH in comparison with lifestyle and dietary modification alone.Trial accession numberClinicalTrial.gov: NCT01950884.     

The Global Burden of Aortic Stenosis

Degenerative, calcific valvular aortic stenosis (AS), caused by an active process of atherosclerosis, calcification and ossification, is the most common cause of AS in industrialized nations. The prevalence of calcific AS is age-dependent, and thus is expected to increase due to demographic aging of the global population. It is well recognized that severe AS carries a poor prognosis if left untreated. Despite this recognition, many patients are inappropriately denied surgery because of perceived risk. This article will examine the etiology, prevalence, and current trends in the treatment of degenerative AS focusing on indications for surgical aortic valve replacement.     

Ezetimibe and Rosuvastatin Combination Treatment Can Reduce the Dose of Rosuvastatin Without Compromising Its Lipid-lowering Efficacy

PurposeThe goal of this study was to compare the lipid-lowering efficacy of the combination of ezetimibe and low- or intermediate-intensity statin therapy versus that of high-intensity statin monotherapy.MethodsThis study is a post hoc analysis of an 8-week, randomized, double-blind, Phase III trial. Patients who had hypercholesterolemia and required lipid-lowering treatment were randomly assigned to 1 of 6 treatment groups: rosuvastatin 5 mg (R5, n = 68), rosuvastatin 10 mg (R10, n = 67), rosuvastatin 20 mg (R20, n = 69), and ezetimibe 10 mg combined with rosuvastatin 5 mg (R5 + E10, n = 67), rosuvastatin 10 mg (R10 + E10, n = 68), and rosuvastatin 20 mg (R20 + E10, n = 68) daily. The effects of coadministration of ezetimibe and a low dose of rosuvastatin on lipid parameters and the target achievement rate were compared between the R5 + E10 and R10 treatment groups, the R5 + E10 and R20 treatment groups, and the R10 + E10 and R20 treatment groups.FindingsReductions in total cholesterol, LDL-C, apolipoprotein B, the apolipoprotein B/A1 ratio, and non–HDL-C were not different between the R5 + E10 and R10 treatment groups (all, P > 0.017), the R5 + E10 and R20 treatment groups (all, P > 0.017), and the R10 + E10 and R20 treatment groups (all, P > 0.017). R5 + E10 treatment showed efficacy comparable to that of R10 or R20 in affording LDL levels <50% of the baseline level (R5 + E10 vs R10, 73.13% vs 62.69% [P = 0.1952]; R5 + E10 vs R20, 73.13% vs 73.91% [P = 0.9180]), LDL-C levels <70 mg/dL (R5 + E10 vs R10, 64.18% vs 55.22% [P = 0.2906]; R5 + E10 vs R20, 64.18% vs 62.32% [P = 0.8220]), and LDL-C levels <50% of the baseline level or <70 mg/dL (R5 + E10 vs R10, 77.61% vs 70.15% [P = 0.3255]; R5 + E10 vs R20, 77.61% vs 78.26% [P = 0.9273]). The R10 + E10 treatment group was better than the R20 treatment group in achieving the target LDL-C level <70 mg/dL (83.82% vs 62.32%; P = 0.0046), even among participants with a baseline LDL-C level >135 mg/dL (77.5% vs 48.8%, respectively; P = 0.0074).ImplicationsEzetimibe combined with low- or intermediate-intensity statin therapy has lipid-lowering efficacy comparable to or better than that of high-intensity rosuvastatin monotherapy. The results of the present study indicate that the combination treatment with ezetimibe is advantageous in that it permits dose reduction of rosuvastatin without compromising the lipid-lowering efficacy of rosuvastatin. ClinicalTrials.gov identifier: NCT02205606.