目的评价Evolocumab降低低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)的有效性及安全性。方法通过电子数据库检索所有评价Evolocumab治疗高LDL-C的随机对照研究,采用RevMan5.2软件对数据进行Meta分析。结果一共纳入...目的评价Evolocumab降低低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)的有效性及安全性。方法通过电子数据库检索所有评价Evolocumab治疗高LDL-C的随机对照研究,采用RevMan5.2软件对数据进行Meta分析。结果一共纳入5项前瞻性随机对照研究,包括1 396个病例。Meta分析结果显示:与安慰剂比较,Evolocumab可显著降低LDL-C(WMD=-55.04,95%CI=-57.45^-52.62,P<0.05)。两组在治疗后转氨酶升高大于3倍正常值上限(OR=0.57,95%CI=0.20~1.61)、肌酸激酶升高大于5倍正常值上限(OR=2.52,95%CI=0.63~10.00)、严重不良事件(OR=1.49,95%CI=0.82~2.73)、因药物不良事件导致停药(OR=1.17,95%CI=0.51~2.72)发生等方面差异均无统计学意义(P>0.05)。结论现有临床试验数据表明,Evolocumab降低LDL-C是安全有效的。展开更多
1文献来源研究一：Sabatine MS,Giugliano RP,Wiviott SD,et al.Efficacy and safety of Evolocumab inreducing lipids and cardiovascular events[J].N EnglJ Med,2015,372（16）：1500-1509.研究二：Robinson JG,Farnier M,Krempf M,
前蛋白转化酶枯草溶菌素9(proprotein convertase subtilisin/kexin type 9,PCSK9)是一种由肝脏合成的丝氨酸激酶,可促使体内低密度脂蛋白胆固醇(LDL-C)累积,抑制PCSK9活性则可使LDL-C水平显著下降。Evolocumab(商品名Repatha)是由美国...前蛋白转化酶枯草溶菌素9(proprotein convertase subtilisin/kexin type 9,PCSK9)是一种由肝脏合成的丝氨酸激酶,可促使体内低密度脂蛋白胆固醇(LDL-C)累积,抑制PCSK9活性则可使LDL-C水平显著下降。Evolocumab(商品名Repatha)是由美国安进公司研发的全球第一个PCSK9抑制剂,2015年7月在欧盟上市,被批准用于治疗原发性和家族性高胆固醇血症。该药的特别之处在于能大幅降低他汀类药物耐受患者体内的LDL-C,因此可有效解决广泛使用他汀类药物后出现的大面积耐药问题。笔者就Evolocumab的基本性质、作用机制、药效学、药动学、临床应用、研发历程等情况作一概述,以期能为医院临床用药及药物开发提供参考。展开更多
Aims: There has been no evidence on the effects of evolocumab, protein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, on small size LDL. We observationally investigated the efficacy and side effects of evolocum...Aims: There has been no evidence on the effects of evolocumab, protein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, on small size LDL. We observationally investigated the efficacy and side effects of evolocumab on the LDL subfraction particle diameter using PAGE system for lipoprotein analysis. Methods: We defined 30 patients with high-risk hyperlipidemia. As for analysis of LDL subfraction profile, we used polyacrylamide gel electrophoresis three methods: 1) 3% nondenatured poly-acrylamide gel electrophoresis method (3%PAGE), 2) 2% - 16% nondenatured poly-acrylamide gradient gel electro-phoresis method (2% - 16% GGE) and 3) 2.7% - 5% GGE. Evolocumab 140 mg/day administered together with statin significantly improved serum total cholesterol (TC), triglyceride (TG), high-dense lipoprotein-cholesterol (HDL-C), and LDL-C after four-week treatment. Results: TC, TG, HDL-C and LDL-C levels were improved by, respectively, 33%, 20%, 10%, and 54%. The mean LDL size significantly increased from 25.6 ± 0.4 nm to 26.4 ± 0.8 nm. The small dense LDL-cholesterol (sdLDL-C), large buoyant LDL-cholesterol (lbLDL-C), and mid-band lipoprotein-cholesterol were reduced, respectively. Therefore, the preliminary study on this paper can be the first step into a new insight on the world of lipid metabolism. Conclusion: Short-term administration of evolocumab addedons to statin therapy, significantly reduced small size LDL levels.展开更多
Background Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 （PCSK9）, significantly reduced low-density lipoprotein （LDL） cholesterol levels in short-term studies. We co...Background Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 （PCSK9）, significantly reduced low-density lipoprotein （LDL） cholesterol levels in short-term studies. We con- ducted two extension studies to obtain longer-term data.展开更多
Background:Evolocumab,a fully human monoclonal antibody directed against proprotein convertase subtilisin-kexin type 9,is widely used in adult patients to lower low-density lipoprotein(LDL)cholesterol levels.Its effec...Background:Evolocumab,a fully human monoclonal antibody directed against proprotein convertase subtilisin-kexin type 9,is widely used in adult patients to lower low-density lipoprotein(LDL)cholesterol levels.Its effects in pediatric patients with heterozygous familial hypercholesterolemia are not known.Methods:We conducted a 24-week,randomized,double-blind,placebo-controlled trial to evaluate the efficacy and safety of evolocumab in pediatric patients with heterozygous familial hypercholesterolemia.Patients 10 to 17 years of age who had received stable lipid-lowering treatment for at least 4 weeks before screening and who had an LDL cholesterol level of 130 mg per deciliter(3.4 mmol per liter)or more and a triglyceride level of 400 mg per deciliter(4.5 mmol per liter)or less were randomly assigned in a 2:1 ratio to receive monthly subcutaneous injections of evolocumab(420 mg)or placebo.The primary end point was the percent change in LDL cholesterol level from baseline to week 24;key secondary end points were the mean percent change in LDL cholesterol level from baseline to weeks 22 and 24 and the absolute change in LDL cholesterol level from baseline to week 24.展开更多
Evolocumab,an inhibitory monoclonal antibody of proprotein convertase subtilisin-kexin type 9(PCSK9),presents as an effective method to decrease low-density lipoprotein cholesterol(LDL-C)and reduce the risk of major a...Evolocumab,an inhibitory monoclonal antibody of proprotein convertase subtilisin-kexin type 9(PCSK9),presents as an effective method to decrease low-density lipoprotein cholesterol(LDL-C)and reduce the risk of major adverse cardiovascular events,which has attracted widespread attention.Compared to statins,it is reported to be more efficient and less restricted to liver function.However,up to now,there has been no relevant reports about the safety of evolocumab in patients with biliary dysfunctions(1).Here,we presented a rare case with an unprecedented complication of evolocumab in a jaundice patient with pancreatic carcinoma,who suffered from short-term recurrent jaundice and acute obstructive suppurative cholangitis(AOSC)due to biliary stent blockage after successful stent implantation.展开更多
文摘目的评价Evolocumab降低低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)的有效性及安全性。方法通过电子数据库检索所有评价Evolocumab治疗高LDL-C的随机对照研究,采用RevMan5.2软件对数据进行Meta分析。结果一共纳入5项前瞻性随机对照研究,包括1 396个病例。Meta分析结果显示:与安慰剂比较,Evolocumab可显著降低LDL-C(WMD=-55.04,95%CI=-57.45^-52.62,P<0.05)。两组在治疗后转氨酶升高大于3倍正常值上限(OR=0.57,95%CI=0.20~1.61)、肌酸激酶升高大于5倍正常值上限(OR=2.52,95%CI=0.63~10.00)、严重不良事件(OR=1.49,95%CI=0.82~2.73)、因药物不良事件导致停药(OR=1.17,95%CI=0.51~2.72)发生等方面差异均无统计学意义(P>0.05)。结论现有临床试验数据表明,Evolocumab降低LDL-C是安全有效的。
文摘1文献来源研究一：Sabatine MS,Giugliano RP,Wiviott SD,et al.Efficacy and safety of Evolocumab inreducing lipids and cardiovascular events[J].N EnglJ Med,2015,372（16）：1500-1509.研究二：Robinson JG,Farnier M,Krempf M,
文摘前蛋白转化酶枯草溶菌素9(proprotein convertase subtilisin/kexin type 9,PCSK9)是一种由肝脏合成的丝氨酸激酶,可促使体内低密度脂蛋白胆固醇(LDL-C)累积,抑制PCSK9活性则可使LDL-C水平显著下降。Evolocumab(商品名Repatha)是由美国安进公司研发的全球第一个PCSK9抑制剂,2015年7月在欧盟上市,被批准用于治疗原发性和家族性高胆固醇血症。该药的特别之处在于能大幅降低他汀类药物耐受患者体内的LDL-C,因此可有效解决广泛使用他汀类药物后出现的大面积耐药问题。笔者就Evolocumab的基本性质、作用机制、药效学、药动学、临床应用、研发历程等情况作一概述,以期能为医院临床用药及药物开发提供参考。
文摘Aims: There has been no evidence on the effects of evolocumab, protein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, on small size LDL. We observationally investigated the efficacy and side effects of evolocumab on the LDL subfraction particle diameter using PAGE system for lipoprotein analysis. Methods: We defined 30 patients with high-risk hyperlipidemia. As for analysis of LDL subfraction profile, we used polyacrylamide gel electrophoresis three methods: 1) 3% nondenatured poly-acrylamide gel electrophoresis method (3%PAGE), 2) 2% - 16% nondenatured poly-acrylamide gradient gel electro-phoresis method (2% - 16% GGE) and 3) 2.7% - 5% GGE. Evolocumab 140 mg/day administered together with statin significantly improved serum total cholesterol (TC), triglyceride (TG), high-dense lipoprotein-cholesterol (HDL-C), and LDL-C after four-week treatment. Results: TC, TG, HDL-C and LDL-C levels were improved by, respectively, 33%, 20%, 10%, and 54%. The mean LDL size significantly increased from 25.6 ± 0.4 nm to 26.4 ± 0.8 nm. The small dense LDL-cholesterol (sdLDL-C), large buoyant LDL-cholesterol (lbLDL-C), and mid-band lipoprotein-cholesterol were reduced, respectively. Therefore, the preliminary study on this paper can be the first step into a new insight on the world of lipid metabolism. Conclusion: Short-term administration of evolocumab addedons to statin therapy, significantly reduced small size LDL levels.
基金Funded by AmgenOSLER-1 and OSLER-2 Clinical Trials.gov numbers,NCT01439880 and NCT01854918
文摘Background Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 （PCSK9）, significantly reduced low-density lipoprotein （LDL） cholesterol levels in short-term studies. We con- ducted two extension studies to obtain longer-term data.
文摘Background:Evolocumab,a fully human monoclonal antibody directed against proprotein convertase subtilisin-kexin type 9,is widely used in adult patients to lower low-density lipoprotein(LDL)cholesterol levels.Its effects in pediatric patients with heterozygous familial hypercholesterolemia are not known.Methods:We conducted a 24-week,randomized,double-blind,placebo-controlled trial to evaluate the efficacy and safety of evolocumab in pediatric patients with heterozygous familial hypercholesterolemia.Patients 10 to 17 years of age who had received stable lipid-lowering treatment for at least 4 weeks before screening and who had an LDL cholesterol level of 130 mg per deciliter(3.4 mmol per liter)or more and a triglyceride level of 400 mg per deciliter(4.5 mmol per liter)or less were randomly assigned in a 2:1 ratio to receive monthly subcutaneous injections of evolocumab(420 mg)or placebo.The primary end point was the percent change in LDL cholesterol level from baseline to week 24;key secondary end points were the mean percent change in LDL cholesterol level from baseline to weeks 22 and 24 and the absolute change in LDL cholesterol level from baseline to week 24.
基金supported by the National High Level Hospital Clinical Research Funding(No.2022-PUMCH-A-186)the Non-profit 121 Central Research Institute Fund of Chinese Academy of 122 Medical Sciences(No.2023-JKCS-01).
文摘Evolocumab,an inhibitory monoclonal antibody of proprotein convertase subtilisin-kexin type 9(PCSK9),presents as an effective method to decrease low-density lipoprotein cholesterol(LDL-C)and reduce the risk of major adverse cardiovascular events,which has attracted widespread attention.Compared to statins,it is reported to be more efficient and less restricted to liver function.However,up to now,there has been no relevant reports about the safety of evolocumab in patients with biliary dysfunctions(1).Here,we presented a rare case with an unprecedented complication of evolocumab in a jaundice patient with pancreatic carcinoma,who suffered from short-term recurrent jaundice and acute obstructive suppurative cholangitis(AOSC)due to biliary stent blockage after successful stent implantation.
