缺血性卒中TIA二级预防中的他汀使用.ppt

,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,二级,三级,四级,五级,*,国家神经系统疾病临床医学研究中心,*,文档仅供参考，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。,A,medical guideline,(also called a,clinical guideline,clinical protocol,or,clinical practice guideline,)is a document with the aim of guiding decisions and criteria regarding,diagnosis,management,and treatment in specific areas of,healthcare.,2026/10/30,1,2026/10/30,2,A New Era in Secondary Stroke Prevention,Updated:May 19,2014,A New Era in Secondary Stroke Prevention,Disclosure:,Dr.Kim-Tenser and Dr.Mack have no relevant disclosures.,Pub Date:,Thursday,May 1,2014,Authors:,May Kim-Tenser,MD,and William J.Mack,MD,MS,FAANS,FAHA,Affiliation:,University of Southern California/Keck School of Medicine,卒,中,二,级,预,防,的,新,纪,元,2026/10/30,4,不同角度看到问题不同,2026/10/30,5,对卒中二级预防他汀指南影响的里程碑,2026/10/30,6,对卒中二级预防他汀指南影响的里程碑,2026/10/30,7,二级预防中的他汀治疗奠基石,16,12,10,8,0,0,1,2,3,4,5,6,Fatal or Nonfatal Stroke(%),Placebo,Atorvastatin,HR,0.84(95%CI,0.71-0.99);,P,=.03,Years Since Randomization,Pierre Amarenco,2026/10/30,8,Mean on-treatment LDL-C:,Placebo=129 mg/dL,Atorvastatin=73 mg/dL,-53%,+1%,-7%,-38%,Baseline LDL-C:133 mg/dL,Amarenco P,Bogousslavsky J,Callahan A III,et al.,N Engl J Med.2006;355:549-59,LDL-C,的变化,HR=0.67(95%CI 0.47,0.94),P,=.02*,0,1,2,3,4,5,70,100,90,80,Patients free of fatal or non-fatal stroke(%),Years since randomization,Placebo,Atorvastatin,*:,adjusted for entry event,time since entry event,gender,age,and geographical region,RR:33%,Sillesen H,Amarenco P,Hennerici MG,et al.,Stroke.2009;40:E-pub,颈动脉狭窄的结局,Note:Percent change effects from Cox proportional hazards models with adjustment for gender and baseline age with reference group=no change or increase,0.4,0.7,1.0,1.3,1.6,1.9,2.2,50%Decrease,50%Decrease,50%Decrease,50%Decrease,50%Decrease,50%Decrease,HR(95%CI),0.89(0.73,1.08),0.69(0.55,0.87),0.90(0.73,1.12),0.67(0.52,0.86),0.84(0.50,1.40),1.04(0.61,1.78),p-value,0.2253,0.0016,0.3394,0.0018,0.4716,0.8864,All Stroke,Ischemic Stroke,Hemorrhagic Stroke,Hazard Ratio(95%CI),0%Increase,1.00,0%Increase,1.00,0%Increase,1.00,Amarenco P,Goldstein LB,Szarek M,et al.,Stroke.2007;38:3198-3204,LDL-C,降低幅度与二级预防,Note:Nominal value effects from Cox proportional hazards models with adjustment for gender and baseline age with reference group=no change or increase,0.4,0.7,1.0,1.3,1.6,1.9,2.2,70 to 100 mg/dL,2,个危险因素，,LDL 120,160mg/dL,，,10,年冠心病风险,10%);HDL-C,60mg/dL;,甘油三酯,500mg/dL;B,超证实颅外颈动脉,CIMT,1.2 and 3.5mm,。,5:2,随机、双盲、安慰剂对照,平均年龄,=57,岁；女性,.40%,R,6,12,18,和,24,个月随访,ACC 2007,METEOR Trial,：血脂变化,%Change(SE),Rosuvastatin(n=624),Placebo(n=252),Lipid levels,mg/dL LDL Cholesterol,48(0.7),0.3(1.1),Total Cholesterol,33.7(0.5),0.3(0.8),HDL Cholesterol,8.0(0.6),2.8(0.9),Triglycerides,15.7(1.4),10.1(2.3),Non-HDL Cholesterol,45.1(0.6),0(0.98),Abbreviations:HDL,high-density lipoprotein;LDL,low-density lipoprotein.SI conversion factors:To convert HDL,LDL,and total cholesterol to mmol/L,multiply by 0.0259;triglycerides to mmol/L,multiply by 0.0113.P.001 for all comparisons of rosuvastatin with placebo.,Crouse JR et al.,JAMA,2007;,297:1344-1353,颈动脉,CIMT,变化,(mm/year),METEOR Trial:,主要终点,n=702,n=282,p 0.001,ACC 2007,Change in maximum CIMT with rosuvastatin vs.placebo,Rosuvastatin,Placebo,*Crouse JR III et al.JAMA 2007;297(12):1344-1353,METEOR,：主要终点,颈总动脉,CMIT,变化,(mm/year),METEOR Trial:,次要终点,n=702,n=282,p 0.001,ACC 2007,Change in maximum CIMT with rosuvastatin vs.placebo,Rosuvastatin,Placebo,颈动脉球部,CIMT(mm/year),METEOR Trial:,次要终点,n=702,n=282,p 0.001,ACC 2007,Change in maximum CIMT with rosuvastatin vs.placebo,Rosuvastatin,Placebo,颈内动脉,CIMT,变化,(mm/year),METEOR Trial:,次要终点,n=702,n=282,p=0.02,ACC 2007,Change in maximum CIMT with rosuvastatin vs.placebo,Rosuvastatin,Placebo,WILMINGTON,Del.,November 09,2007/PRNewswire-FirstCall/-AstraZeneca announced today that the U.S.Food and Drug Administration(FDA)has approved,Crestor(rosuvastatin calcium)as an adjunct to diet to slow the progression of atherosclerosis in patients with elevated cholesterol.This new indication gives Crestor an important differentiator from competitors in the cholesterol-lowering marketplace.,FDA Approves New Indication for Crestor,Crestor Now Indicated to Slow the Progression of Atherosclerosis in Patients With Elevated Cholesterol,2026/10/30,23,陈韵岱,王拥军,METEOR-China,2026/10/30,24,对卒中二级预防他汀指南影响的里程碑,2026/10/30,25,2011,年,AHA/ASA,卒中二级预防指南：,强化降脂，达标“,5018,”,Furie KL,et al.Stroke 2011;42;227-276;,Guidelines for the Prevention of Stroke in Patients With Stroke or Transient Ischemic Attack,对于伴有动脉粥样硬化性缺血性卒中,/TIA,，但无已知冠心病的患者：,LDL-C,应降低,50%,或,LDL-C70mg/dL(1.8mmol/L),以将获益最大化,对卒中二级预防他汀指南影响的里程碑,2026/10/30,27,S,tenting and,A,ggressive,M,edical,M,anagement for,P,reventing,R,ecurrent stroke in,I,ntracranial,S,tenosis,颅内动脉狭窄为预防再发卒中,的支架和积极药物治疗,SAMMPRIS,设计,SAMMPRIS,中积极药物治疗,(AMM),方案,简单、明确的干预目标和方案,阿司匹林,325 mg/d,氯吡格雷,75 mg/d,治疗,90,天,危险因素干预目标和方案,主要危险因素,LDL-C,70 mg/dl,SBP,140 mmHg,次要危险因素,非,HDL-C,100 mg/dl,HbA1c,7.0%,吸烟,停止,体重,BMI25-27,目标,27,目标体重减轻,10%,运动,30,分钟，,3x/wk,生活方式干预方案,提供个体化危险因素咨询途径（电话），前,12,周每月,2,次，以后每月,1,次,为患者提供书面反馈，帮助患者达到次要危险因素控制目标,积极药物治疗,(AMM),SAMMPRIS,：他汀使用策略,Derdeyn CP,et al.,Lancet.2014 Jan 25;383(9914):333-41.,*,亚洲人群起始剂量为,10mg,下面情况不适用瑞舒伐他汀：,对瑞舒伐他汀过敏,肌酐清除率,30ml/min,他汀药物治疗：瑞舒伐他汀,20/40mg,32,SAMMPRIS,：,LDLC,变化,Derdeyn CP,et al.,Lancet.2014 Jan 25;383(9914):333-41.,药物治疗组,PTAS,组,n,平均（,SD,）,n,平均（,SD,）,基线,226,2.53(0.95),220,2.49(0.99),30,天,215,1.85(0.69),210,2.01(0.73),4,个月,193,1.84(0.67),186,1.96(1.03),1,年,138,1.75(0.71),138,1.79(0.76),2,年,95,1.61(0.58),100,1.74(0.80),3,年,39,1.74(0.66),45,1.74(0.79),LDL-C,水平,(mmol/L),33,SAMMPRIS,结果,颅内动脉狭窄的临床试验,WASID(2005),SAMMPRIS(2011),TOSS(2011),治疗组,华法林（,n=289)/ASA(n=280),AMM(n=227),支架,(n=224),ASA+,氯吡格雷,(n=225)/ASA+,西罗他唑,(n=232),病人,狭窄,50-99%,狭窄,70-99%,MRA,上狭窄,卒中后随机,90,天,30,天,14,天,随访时长,1.8,年,1,年,7,月,主要终点,21.8%,22.1%,12.2%/20.0%,4.4%/6.5%,危险因素控制（基线,随访）,收缩压,140mmHg,55,5,3%,平均,147,135mmHg,LDL-C,100mg/dL,29,56%,40mg/dL,64,6,3%,平均，,38,4,2mg/dL,平均，,43,49mg/dL,HbA1C,7%,32,52%,平均，,8.3,7.,5%,平均，,6,.7,6.2%,2026/10/30,35,颅内动脉粥样硬化是我国卒中的常见病因,Stroke.2014;45:663-669,2026/10/30,36,对卒中二级预防他汀指南影响的里程碑,2026/10/30,37,2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults,AMERICAN,COLLEGE,of,CARDIOLOGY,Trial Data,Statin vs.Control,SSSS,HPS,ALLIANCE,CARDS,JUPITER,ASCOT-LLA,Post-CABG,WOSCOPS,PROSPER,CARE,LIPID,ASPEN,AURORA,AFCAPS/TexCAPS,LIPS,GISSI-HF,4D,ALERT,MEGA,ALLHAT-LLT,GISSI-P,More vs.Less Statin,PROVE-IT,TNT,IDEAL,SEARCH,A to Z,Yes,Yes,No,No,No,No,Yes,Yes,Yes,Calculate 10-yr ASCVD risk using Pooled Cohort Equations,Adults 21 years of age and candidate for statin,Clinical ASCVD?,LDL-C,190 mg/dL?,Diabetes?,7.5%10-yr ASCVD risk?,High-intensity statin,(Moderate-intensity if 75 yo or not candidate for high-intensity statin),High intensity statin,(Moderate-intensity if not candidate for high-intensity),Moderate-intensity statin,(High-intensity if 10-yr ASCVD risk,7.5%),Moderate-to-high intensity statin,ASCVD prevention benefit less clear,but may be considered,Statin intensity,High,Intensity,(Lowers,LDL-C by,50%),Moderate-Intensity,(Lowers LDL-C by 30-50%),Low-Intensity,(Lowers,LDL-C by 30%),Atorvastatin 40-80 mg,Rosuvastatin,20-,40,mg,Atorvastatin 10-20 mg,Rosuvastatin,5-10 mg,Simvastatin 20-40 mg,Pravastatin 40-80 mg,Lovastatin 40 mg,Fluvastatin 40 mg BID,Pitavastatin 2-4 mg,Simvastatin 10 mg,Pravastatin 10-20 mg,Lovastatin 20 mg,Fluvastatin 20-40 mg,Pitavastatin 1 mg,Statins and doses listed in italics are approved for use but have not been studied in randomized controlled trials.Adapted from Stone NJ,et al.2013 ACC/AHA Blood Cholesterol Guideline.,对卒中二级预防他汀指南影响的里程碑,2026/10/30,42,2014AHA/ASA,新指南：血脂管理推荐,Kernan WN,et al.Stroke,July 2014,Stone NJ,et al.Circulation.2013 Nov 12.Epub ahead of print,强调综合危险因素控制,如控制血压、胆固醇、体重和体育锻炼，,目的是降低卒中再发及其他心血管事件风险,基于,2013ACC/AHA,减少成人动脉粥样硬化性心血管风险血胆固醇治疗指南,，提出重要的新推荐和修订,新指南中关于血脂异常管理的新推荐,与,2013ACC/AHA,胆固醇指南的精神保持一致,对动脉粥样硬化源性缺血性卒中,/TIA,患者：推荐强化他汀治疗,Kernan WN,et al.Stroke,July 2014,*基于,2013ACC/AHA,指南进行的内容修订,对,动脉粥样硬化源性缺血性卒中或,TIA,且,LDL-C100mg/dl,的患者,，无论是否存在其他临床,ASCVD,证据，,推荐使用强化他汀治疗,以降低卒中和心血管事件风险,（内容修订*）,I,，,B,对,动脉粥样硬化源性缺血性卒中或,TIA,且,LDL-C100mg/dl,的患者,，无其他临床,ASCVD,证据，,推荐使用强化他汀治疗,以降低卒中和心血管事件的危险,（新推荐）,I,，,C,对,缺血性卒中或,TIA,并合并其他,ASCVD,的患者，,应,根据,2013 ACC/AHA,指南进行管理,，包括改变生活方式、饮食控制和推荐的药物治疗,（内容修订*）,I,，,A,*基于,2013ACC/AHA,指南进行的内容修订,对伴颅内、外动脉粥样硬化狭窄的,IS/TIA,患者：推荐综合危险因素控制，强化他汀治疗是基石,认为主动脉弓动脉粥样硬化是缺血性卒中和,TIA,的重要病因。对缺血性卒中或,TIA,并,存在主动脉弓动脉粥样硬化斑块,的患者，,推荐他汀治疗,I,，,B,颅内动脉粥样硬化,：对由主要,颅内动脉,50%,99%,狭窄,引起的缺血性卒中或,TIA,患者，,推荐,血压维持在,140mmHg,以下和,强化他汀治疗,I,，,B,颅外颈动脉疾病,：对所有,颈动脉狭窄合并,TIA,或缺血性卒中,患者，,推荐优化药物治疗,包括抗血小板治疗、,他汀治疗,和纠正危险因素,I,，,A,颅外椎基底动脉疾病,：对所有近期发生,症状性颅外椎基底动脉狭窄,的患者，,推荐进行常规预防治疗,，重点为抗栓治疗、,降脂,、控制血压和优化生活方式,I,，,C,Kernan WN,et al.Stroke,July 2014,2014,AHA/ASA,新指南：,他汀尤其是强化他汀治疗的人群进一步扩大,2011,年,AHA/ASA,卒中二级预防指南,2014,年,AHA/ASA,卒中二级预防指南,缺血性卒中或,TIA,患者，如,胆固醇高，或者同时患有,CHD,所有有,颈动脉狭窄,的,TIA,或卒中患者,无,CHD,史,的缺血性卒中或,TIA,患者，,如,有动脉粥样硬化证据,、,LDL-C100 mg/dl(2.6 mmol/L),缺血性卒中或,TIA,并,合并其他,ASCVD,的患者,所有有,颈动脉狭窄,的,TIA,或卒中患者,动脉粥样硬化源性,缺血性卒中或,TIA,患者,无论胆固醇水平,不仅限于合并,CHD,相同,颅内动脉,50,99%,狭窄,引起的缺血性卒中或,TIA,患者,对缺血性卒中或,TIA,并存在,主动脉弓动脉粥样硬化斑块,的患者,无论,LDL-C,水平,无论是否有,CHD,病史,新增人群,Furie KL,et al.Stroke 2011,Kernan WN,et al.Stroke,July 2014,Treat Stroke to Target(TST),Pierre Amarenco,从,SPARCL,到,TST,2026/10/30,47,理想多靶值,LDL-C 70 mg/dL(NCEP-III,high risk),TG 50 mg/dL(NCEP-III),BP 120/80 mm Hg(JNC-7),Amarenco P,Goldstein LB,Messig M,et al.Stroke.2009,Combined Effect of Optimal Lipid&BP Control on Risk of Stroke and MCVE,Stroke,0 parameters,1 parameter,2 parameters,3 parameters,4 parameters,Major cardiovascular events(MCVE),0 parameter,1 parameters,2 parameters,3 parameters,4 parameters,No.subjects,662,1156,1926,906,80,662,1156,1926,906,80,No(%)events,93(14.0)167(14.4),228(11.8)84(9.3),4(5.0),126(19.0),207(17.9),290(15.1),114(12.6),4(5.0),HR,1.00,0.982,0.782,0.620,0.354,1.000,0.9030.7250.603,0.247,95%CI,(0.761,1.266),(0.612,0.998),(0.459,0.837),(0.130,0.963),(0.723,1.128),(0.587,0.896),(0.466,0.781),(0.091,0.669),P,-value,0.8859,0.0478,0.0018,0.0420,0.3704,0.0029,0.0001,0.0059,Overall,P,-value*,0.0012,0.0001,0.0,0.5,1.0,1.5,*P value for differences between number of parameters achieved,Amarenco P,et al.Stroke.2009,对卒中二级预防他汀指南影响的里程碑,2026/10/30,50,谢谢,Thanks,2026/10/30,51,