他汀临床应用指南

Klicka hr fr att ndra format p bakgrundsrubriken,Klicka hr fr att ndra format p bakgrundstexten,Niv tv,Niv tre,Niv fyra,Niv fem,#,Name, department,*,Klicka hr fr att ndra format p bakgrundsrubriken,Klicka hr fr att ndra format p bakgrundstexten,Niv tv,Niv tre,Niv fyra,Niv fem,#,Name, department,*,Klicka hr fr att ndra format p bakgrundsrubriken,Klicka hr fr att ndra format p bakgrundstexten,Niv tv,Niv tre,Niv fyra,Niv fem,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,他汀临床应用指南,冠心病的分型,急性冠脉综合症（,ACS,）,不稳定型心绞痛（,UA,）,非,ST,段抬高性心肌梗死（,NSTEMI,）,ST,段抬高性心肌梗死（,STEMI,）,冠心病猝死,慢性冠心病,稳定型心绞痛,冠脉正常的心绞痛（如,X-,综合征）,无症状性心肌缺血,缺血性心力衰竭（缺血性心肌病）,III,级和,IV,级,GRACE,评分,100,高危冠心病！,各型冠心病指南的危险分层与他汀,/,血脂治疗原则,指南分类（冠心病类型）,国际指南及发表时间,国内指南相关文献及发表时间,慢性稳定型心绞痛,ACC/AHA2007,、,ESH/ESC2007,中华心血管病杂志,2007.3,不稳定性心绞痛和非,ST,段抬高心肌梗死,ACC/AHA2007,、,ESH/ESC2007,中华心血管病杂志,2007.4,急性,ST,段抬高型心肌梗死,ACC/AHA2007,、,ACC/AHA2009,、,ESH/ESC2008,中华心血管病杂志,2010.8,冠心病及其他粥样硬化性血管病,二级预防,ACC/AHA 2006 update,慢性稳定性心绞痛诊断和治疗指南,心绞痛严重度分级（参照加拿大心血管学会（,CCS,）心绞痛严重度分级）,危险分层可根据临床评估，对负荷试验的反应，左心室功能及冠状动脉造影显示的病变情况综合判断,中华心血管病杂志,2007,年,3,月第,35,卷第,3,期,慢性稳定性心绞痛诊断和治疗指南,他汀,/,血脂治疗原则,改善预后的药物治疗建议（一）,I,类,所有,冠心病稳定性心绞痛患者接受他汀类药物治疗，,LDL-C,的目标值（,100mg/dl,）（证据水平,A,）,IIa,类,有明确冠状动脉疾病的,极高危患者,（,年心血管死亡率,2%,）接受强化他汀类药物治疗，,LDL-C,的目标值（,80mg/dl,） （证据水平,A,）,IIb,类,糖尿病或代谢综合症合并低,HDL-C,和高甘油三酯血症的患者接受贝特类或烟酸类药物治疗（证据水平,B,）,中华心血管病杂志,2007,年,3,月第,35,卷第,3,期,血脂不高的稳定型心绞痛患者还需要服用他汀吗？,2002 ACC AHA for Stable Angina,2007 ACC AHA for Stable Angina,LDL-C,保持在,100,mg/dL,以下，胆固醇不易流入斑块,粥样病变体积百分比 (,PAV),的变化（）,病变进展,-,1,-,0,1,2,50,60,70,80,90,100,110,120,A,-,Plus,2,安慰剂,ACTIVATE,1,安慰剂,CAMELOT,4,安慰剂,REVERSAL,5,普伐他汀,REVERSAL,5,阿托伐他汀,平均,LDL,-,C (mg/,dL,),病变减退,PERISCOPE=,吡格列酮,LDL-C100mg/dL,时胆固醇酯能够流入斑块,JAMA. 2008;299(13):1561-73,LDL-C75mg/dL,提示无斑块进展,P&M CSA=,斑块和中膜,(P&M),横断面(,CSA),Von Birgelen C, et al.,Circulation. 2003;108(22):2757-62,不稳定性心绞痛和非,ST,段抬高心肌梗死危险性分层,中华心血管病杂志,2007,年,4,月第,35,卷第,4,期,全球急性冠脉动脉事件注册（,GRACE,）危险评分系统,GRACE,危险评分系统,低危患者（,0-99,分）,高危患者（,100,）,中华心血管病杂志,2007,年,4,月第,35,卷第,4,期,不稳定性心绞痛和非,ST,段抬高心肌梗死诊断与治疗指南,他汀,/,血脂治疗原则,他汀类药物在,ACS,中的应用,目前已有较多的证据,(PROVE IT,、,A to Z,、,MIRACL,等,),显示，在,ACS,早期,给予他汀类药物，可以改善预后，降低终点事件，,这可能和他汀类药物抗炎症及稳定斑块作用有关,。因此,ACS,患者应在,24 h,内检查血脂，在出院前尽早给予较大剂量他汀类药物。,出院后的药物治疗,改善预后：如阿司匹林、,B,受体阻滞剂、,调脂药物,(,特别是他汀类药物,),、,ACEI(,特别对,LVEF0,40,的患者,),、糖尿病等,ACS,患者包括血管重建治疗的患者，,出院后应坚持口服他汀类降脂药物和控制饮食,，,LDL-C,目标值,2,59 mmol,L(100 mg,m),，高危患者可将,LDL-C,降至,2,07 mmol,L(80 mg,dn),以下,(,证据水平,A),。,中华心血管病杂志,2007,年,4,月第,35,卷第,4,期,？,2007 ACC AHA for UA and NSEMI,There is a wealth of evidence that cholesterol-lowering therapy for patients with CAD and hypercholesterolemia or with mild cholesterol elevation (mean 209 to 218 mg per dL) after MI and UA reduces vascular events and death.,Moreover, recent trials have provided mounting evidence that statin therapy is beneficial regardless of whether the baseline LDL-C level is elevated.,More aggressive therapy has resulted in suppression or reversal of coronary atherosclerosis progression and lower cardiovascular event rates, although the impact on total mortality remains to be clearly established. These data are discussed more fully elsewhere.,ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/NonST-Elevation Myocardial Infarction,。,Journal of the American College of Cardiology Vol. 50, No. 7, 2007,。,急性,ST,段抬高型心肌梗死诊断和治疗指南,中华心血管病杂志,2010,年,8,月第,38,卷第,8,期,冠状动脉及其他动脉硬化性血管病二级预防指南,-,2006 AHA/ACC Guidelines for Secondary Prevention for Patients With Coronary and Other Atherosclerotic Vascular Disease,Furthermore, if it is not possible to attain LDL-C 70 mg/dL because of a high baseline LDL-C, it generally is possible to achieve LDL-C reductions of 50% with either statins or LDL-C lowering drug combinations.,-,LDL-C20%,）,100mg/dL,(,可选目标：,70mg/dL,，尤其是极高危患者,),100mg/dL#,100mg/dL,(100mg/dL;,可选考虑药物,),中等高危：,2,危险因素（,10,年风险,10,20,）,130mg/dL,(,可选目标：,100mg/dL),130mg/dL#,130mg/dL,(100-129md/dL;,可选考虑药物,),中等风险：,2,危险因素（,10,年风险,10%,）,130mg/dL,130mg/dL,160mg/dL,低危：,0,1,危险因素,160mg/dL,160mg/dL,190mg/dL,(160-190mg/dL,；可选考虑降,LDL,药物,NCEP Report. Circulation. 2004:110;227-39,2004 ATP III Update,危险分层以及治疗性生活方式改变和药物治疗的目标值和切点,Exp Opin Emerg Drugs 2004;9(2):269-79,N Engl J Med 2005;352:1425-35,LDL-C mg/dL (mmol/L),WOSCOPS Placebo,AFCAPS - Placebo,ASCOT - Placebo,AFCAPS - Rx,WOSCOPS - Rx,ASCOT - Rx,4S - Rx,HPS - Placebo,LIPID - Rx,4S - Placebo,CARE - Rx,LIPID - Placebo,CARE - Placebo,HPS - Rx,0,5,10,15,20,25,30,40,(1.0),60,(1.6),80,(2.1),100,(2.6),120,(3.1),140,(3.6),160,(4.1),180,(4.7),Event rate (%),6,二级预防,一级预防,Rx - Statin therapy,PRA pravastatin,ATV - atorvastatin,200,(5.2),PROVE-IT - PRA,PROVE-IT ATV,TNT ATV10,TNT ATV80,NCEP 2001,NCEP 2004,LDL-C,水平与冠心病事件密切相关,Lower is Better,中国成人血脂异常防治指南,强调：严格分层治疗，降低心血管事件,危险等级,治疗目标值,mg/dL (mmol/L),低危,:,（,10,年危险性,5%,）,LDL-C160 (4.14),中危,:,（,10,年危险性,5%-10%,）,LDL-C130 (3.37),高危,:,1),冠心病或其等危症,2) 10,年危险性,10-15%,LDL-C100 (2.59),极高危,:,1),急性冠脉综合征,2),缺血性心血管疾病,+,糖尿病,LDL-C80 (2.07),中华心血管病杂志,2007;35(5):390-413,冠心病等危症包括缺血性脑卒中、周围动脉疾病、症状性颈动脉病、糖尿病等,慢性稳定性心绞痛诊断和治疗指南,他汀,/,血脂治疗原则,改善预后的药物治疗建议（一）,I,类,所有,冠心病稳定性心绞痛患者接受他汀类药物治疗，,LDL-C,的目标值（,100mg/dl,）（证据水平,A,）,IIa,类,有明确冠状动脉疾病的,极高危患者,（,年心血管死亡率,2%,）接受强化他汀类药物治疗，,LDL-C,的目标值（,80mg/dl,） （证据水平,A,）,IIb,类,糖尿病或代谢综合症合并低,HDL-C,和高甘油三酯血症的患者接受贝特类或烟酸类药物治疗（证据水平,B,）,中华心血管病杂志,2007,年,3,月第,35,卷第,3,期,JACC 2008;51(15):1512-1524,ACC/ADA,共同指出：血脂控制力度还需加大,危险程度,目标值,LDL-C,Non-HDL-C,(mg/dL),ApoB,(mg/dL),极高危患者,包括：,1),已知,CVD,；,2),糖尿病，合并至少一个其它主要,CVD,危险因素,70mg/dL,(,1.8mmol/L,),100,80,高危患者,包括：,1),无糖尿病或已知的临床,CVD,，但至少有两个其它主要,CVD,危险因素；,2),糖尿病，但无其它主要,CVD,危险因素,100mg/dL,(,2.6mmol/L,),130,90,对有心血管代谢危险因素和血脂异常的患者，推荐的治疗目标值：,其它主要,CVD,危险因素（血脂异常以外），包括：吸烟、高血压、,CAD,早发的家族史,2009,加拿大成人血脂异常及心血管疾病防治指南,高危患者的血脂管理不设起始值,胆固醇管理更积极：新增了,LDL-C,的降低幅度应,50%,心血管风险水平,启动治疗,首要目标,LDL-C,其他,高危,冠心病；外周血管病；有动脉粥样硬化证据,(,所有动脉，包括颈动脉,),；糖尿病；,Framingham,评分,20%,；,Reynolds,评分,20%,一经诊断立即启动,2mmol/L,或在基线水平上降低幅度,50%,（,类推荐）,ApoB3.5mmol/L,；或,TC/HDL-C 5.0,；或,hs-CRP 2 mg/L,；或男性,50,岁；或女性,60,岁；或家族史,2mmol/L,或在基线水平上降低幅度,50%,（,IIa,类推荐）,ApoB0.80g/L,（,IIa,类推荐）,低危,Framingham,评分,20%,）,100mg/dL,(,可选目标：,70mg/dL,，尤其是极高危患者,),100mg/dL#,100mg/dL,(100mg/dL;,可选考虑药物,),中等高危：,2,危险因素（,10,年风险,10,20,）,130mg/dL,(,可选目标：,100mg/dL),130mg/dL#,130mg/dL,(100-129md/dL;,可选考虑药物,),中等风险：,2,危险因素（,10,年风险,10%,）,130mg/dL,130mg/dL,160mg/dL,低危：,0,1,危险因素,160mg/dL,160mg/dL,190mg/dL,(160-190mg/dL,；可选考虑降,LDL,药物,NCEP Report. Circulation. 2004:110;227-39,2004 ATP III Update,危险分层以及治疗性生活方式改变和药物治疗的目标值和切点,血脂指南仍阻碍了他汀的正确应用？,How low should we go?,Can LDL-C be too low?,定期查血，发现血脂异常,首选生活方式干预，改善血脂,血脂化验单哪项异常，就选针对哪项异常的药物,血脂正常或达标后就,减量或停药,基线血脂水平正常就不需要调脂药物,基线血脂水平偏低，就不能用降脂药物,血脂治疗现场直击：,LDL-C,目标值？,JACC 2008;51(15):1512-1524,2008,年,ACC/ADA,共识：为防治动脉粥样硬化,理论上所有人应控制,LDL-C,在,50mg/dL,动物和人体的饮食和药物干预试验显示，,LDL-C,降低的幅度与动脉粥样硬化病变的稳定和逆转有关，这进一步支持了,LDL-C“,低一点，好一些”的观点，特别是在已经明确,CVD,的患者中。,理论上，所有人都应该将,LDL-C,维持在,50mg/dL,的“新生儿”水平，以预防动脉粥样硬化，,CVD,患者也应该控制在类似低的水平。,Brunzell JD, et al. J Am Coll Cardiol. 2008;51(15):1512-24,期待,2011 AHA,，,in Nov. at Orlando, USA!,不论基线血脂水平如何，他汀治疗均显著改善预后（,Jupiter,亚组分析）,多个试验纳入标准没有要求血脂异常,Asteroid,研究：不设基线血脂水平，基线,；以,20%,管腔狭窄,50%,入排；,Care,研究：,4159,名，基线,LDL-C139mg/dl,，普伐他汀,40mg,治疗,5,年，冠心病,+,平均血脂水平，心血管事件显著减少；,LIPID,研究：冠心病血脂基本正常者长期使用他汀显著减少严重不良心血管事件,。,他汀不仅仅是治疗高脂血症的降脂药！,他汀抗动脉粥样硬化作用,多效性；稳定,/,逆转斑块,而目前所有指南仍然强调,100/70,（,80,）。,在控制危险因素的基础上控制动脉粥样硬化,控制危险因素达标（遵循指南） 管理,AS,More Intensive Therapy,Beginning in 2001, when we began to understand the implications of,our findings published in 2002, we implemented in our clinic a,change to treating arteries rather than simply treating risk factor,levels. By 2003, this change in approach had been fully implemented;,the time required to implement the change was determined,by the schedule of follow-up visits. Our approach to intensive,therapy for accelerated atherosclerosis has previously been described.,At baseline, therapy was intensified for those with a high,plaque burden. During follow-up, therapy was intensified in patients,in whom plaque was progressing,despite treatment aimed at consensus,targets for risk factors such as blood pressure and LDL,cholesterol.,This included using plaque measurements to motivate,patients and to inform physicians about choices of medications,J. David Spence, et. al. Stroke. 2010;41:00-00.),In patients with plaque progression, we increased the dose of statin to the maximum tolerated dose, regardless of LDL levels (eg, atorvastatin 80 mg or rosuvastatin 40 mg). In patients already at their,maximum tolerated dose of statin, we added ezetimibe 10 mg daily.,In those already using the maximum dose of statin and ezetimibe, we added niacin for patients who were not diabetic or adding fibrates for diabetic patients or those unable to use niacin or slow-release niacin because of flushing.,J. David Spence, et. al. Stroke. 2010;41:00-00.),J. David Spence, et. al. Stroke. 2010;41:00-00.),160mg/dl,54mg/dl,83mg/dl,55mg/dl,By exceeding guideline-advocated treatment targets,based on serial carotid plaque area measurement, we were able to,reduce the proportion of patients with progression of plaque by half,.,This also,reduced cardiovascular events,. Among our patients with asymptomatic carotid stenosis, thecombined outcome of stroke, death, myocardial infarction, or carotid endarterectomy (because of new cerebral symptoms on the side of the stenosis),declined from 17.6% before 2003 to 5.2% (,P0.0001) since then.,Carotid plaque burden assessed as,TPA,strongly predicted cardiovascular risk after adjusting for coronary risk factors, and that,plaque progression despite treatment according to guidelines further predicted cardiovascular risk.,J. David Spence, et. al. Stroke. 2010;41:00-00.),他汀的三级跨越,治疗高脂血症的降脂药,兼顾,LDL-C/HDL-C/TG,的调脂药,抗动脉粥样硬化,/,防治心血管事件,的药物,（抗,AS,领域的“青霉素”）,CVD,高危患者中富含甘油三酯脂蛋白和,HDL-C:,管理的证据与指导,2011,年,4,月,29,日，,ESC,发布的最新指南，强调对于,LDL-C,达标的,CVD,高危患者，应强调富含甘油三酯脂蛋白,(TRL),及,HDL-C,的管理的重要性；只有综合调脂，才能进一步降低事件风险。,背 景,心血管疾病,CVD,降低,LDL-C,降压,预防血栓,生活方式干预,加药物,当前,CVD,的最佳治疗,即使,LDL-C,达标后，,CVD,高危患者的,CVD,事件风险依然很高,TRL,水平高和,HDL-C,水平低亦是,CVD,危险因素,CV-1106-CR-0013,TRL,和,HDL-C,的病理生理机制,TRL,HDL-C,穿过动脉内膜，与结缔组织基质结合，并被巨噬细胞吞噬，形成泡沫细胞,促进细胞内胆固醇外流、抗炎及抗氧化作用,动脉粥样硬化形成和发展,促,抗,CVD,高危患者的血脂管理路径,LDL-C,水平达标、伴和（或）的,CVD,高危患者,强化生活方式干预,评估其他潜在病因,评估患者治疗依从性,治疗效果不佳，患者血脂水平仍为和（或）,强化降,LDL-C,治疗，如在他汀类药物基础上加用依折麦布,考虑联合应用其他类调脂药物，如烟酸类或贝特类药物,CVD,高危患者的血脂控制目标,血脂控制目标,LDL-C,高危患者：,2.5 mmol/L (100 mg/dL),极高危患者：,2 mmol/L (80 mg/dL),TG,1.0 mmol/L (40 mg/dL),女性：,1.2 mmol/L (45 mg/dL),Non-HDL-C,2,07 mmol,L,（,80mg/dl,） ，应将,LDLC,降至,2,07 mmol,L,以下或使,LDL-C,下降幅度,40,(I,级推荐，,A,级证据,),。,(3),对于有,颅内外大动脉粥样硬化性易损斑块或动脉源性栓塞证据的缺血性脑卒中和,TIA,患者，推荐尽早启动强化他汀类药物治疗,，建议目标,LDL-C,40,(III,级推荐，,c,级证据,),。,(4),长期使用他汀类药物总体上是安全的。他汀类药物治疗前及治疗中，应定期监测肌痛等临床症状及肝酶,(,谷氨酸和天冬氨酸氨基转移酶,),、肌酶,(,肌酸激酶,),变化，如出现监测指标持续异常并排除其他影响因素，,应减量或停药观察,(,供参考：肝酶,3,倍正常上限，肌酶,5,倍正常上限时停药观察，,I,级推荐，,A,级证据,),；,老年患者,如合并重要脏器功能不全或多种药物联合使用时，应注意合理配伍并监测不良反应,(,级推荐，,C,级证据,),。,(5),对于有,脑出血病史或脑出血高风险人群应权衡风险和获益，建议谨慎使用他汀类药物,(,级推荐，,B,级证据,),。,Others,Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack, 2010,Guidelines for the primary prevention of stroke, 2011,中国高血压防治指南，,2005,中国经皮冠状动脉介入治疗指南，,2009,Dyslipidemia and CKD,他汀是我国,PCI,患者围手术期的常用药物之一,刘小慧等,.,中华医学杂志,.2008;88(4):236-9.,CV-1103-CR-0012,那些患者应该长期使用他汀？,总原则：指南,+,新循证,高胆固醇血症？,冠心病伴高胆固醇血症？,胆固醇不高的冠心病病人？,没有冠心病，胆固醇也不高的病人？（,hsCRP,）,高血压，糖尿病，代谢综合症等心血管高危因素病人？,对于下列病人，不论基线血脂水平，均应常规、足量、长期（可能终身）使用他汀，除非禁忌：,所有,CHD,、,CHD,等危症、卒中、周围动脉疾病病人；,具有高血压、糖尿病，高胆固醇血症等,CVD,危险因素的病人,所有无症状的动脉粥样硬化病人,所有容易发生,CVD,不良事件的病人（如,hsCRP,升高）,Thanks!,Thank You !,不尽之处，恳请指正！,