降脂治疗新趋势课件

,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,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。,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,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。,降低,LDL-C,是调脂治疗的首要目标,降低,LDL-C,治疗显著降低了不同水平的总胆固醇水平,显著降低了心血管危险人群的冠心病发病率和死亡率,降低,LDL-C,不是调脂治疗的唯一目标,降低,LDL-C,仅使非致死性,MI,和死亡减少,30%,使用他汀的患者仍可再发冠脉事件,全面调脂策略,降低,LDL-C,、,TG,、,LP(a) +,升高,HDL-C,降低LDL-C是调脂治疗的首要目标,调脂治疗首要目标,强化降脂,降低,LDL-C,他汀革命, 调脂治疗首要目标,Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators,4731,例无冠心病史的缺血性脑卒中或,TIA,的患者,首项通过降脂治疗对此类患者进行二级预防的前瞻性随机,双盲试验,结果,:,卒中后早期给予阿托伐他汀,(80 mg/d),可使患者,5,年内,发生二次卒中的危险降低,16%,N Engl J Med 2006, 355(6): 549(2006,十大医学进展）,Stroke Prevention by Aggressiv,Vulnerable Plaque,“ Active Volcano”,Thrombotic,effect,ACS,Calcified Plaque,“ Dormant Volcano ”,Hemodynamic,effect,Stable Angina,2,Clinical Presentations of Coronary Disease,Vulnerable Plaque Calcified Pl,Progression of Coronary Atheroma,Progression of Coronary Athero,降脂治疗新趋势课件,Most AMI occurs with mildly stenotic plaques,Fact or Fiction ?,Most AMI occurs with mildly s,降脂治疗新趋势课件,降脂治疗新趋势课件,降脂治疗新趋势课件,降脂治疗新趋势课件,降脂治疗新趋势课件,降脂治疗新趋势课件,Systemic Biomarkers for Plaque Inflammation,Systemic Biomarkers for Plaque,他汀,*,LDL-C,下降,乳糜微粒和,VLDL,残余,IDL, LDL-C,的下降,恢复内皮功能,维护平滑肌细胞,抗炎作用,减少血栓形成,内腔,脂质核心,巨噬细胞,平滑肌细胞,ACS,患者他汀治疗获益的原理,*,关于以上,4,项作用和作用机理， 他汀之间有显著的差异。,他汀*LDL-C 下降乳糜微粒和 恢复内皮功能内腔脂质核心巨,血脂管理的进程,Adapted from Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults,JAMA,2001;285:2486-2497;,Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults,JAMA,1993;269:3015-3023;,NCEP Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults,Arch Intern Med,1988;148:36-69.,只关注,LDL-C,的下降,强烈支持树脂和烟酸,他汀和菲诺贝特不作为一线用药,NCEP ATP I,1988,危险评估指导治疗,冠心病的,LDL-C,治疗目标,(,2.6 mmol/L),在高脂血症的治疗上,他汀为 “主要药物,”,菲诺贝特为联合治疗,NCEP ATP II,1993,降,LDL-C,作为高危患者的起始治疗,冠心病等危症,LDL-C,降到,2.6 mmol/L,降,L,DL-C and TG,作为治疗目标,NCEP ATP III,2001,低,-,中等剂量的单种药物治疗,高剂量他汀,考虑联合治疗,中,-,高剂量的他汀,血脂管理的进程Adapted from Expert Pan,Target,100,mg/dL,NCEP ATP III : LDL-C Goals (2004 Updates),LDL-C level,*,Therapeutic option in very high-risk patients and in patients with high TG, non-HDL-C20% ),Moderately,High Risk,2 risk,factors,( 10-yr risk,10-20% ),Moderate,Risk,Lower,Risk,2 risk,factors,( 10-yr risk,10% ),2 risk,factors,Target,130,mg/dL,or,optional,100,mg/dL*,Target,130,mg/dL,Target,160,mg/dL,Grundy SM,et al. Circulation,2004;,110,:227-239,TargetNCEP ATP III : LDL-C Goa,强化降脂逆转动脉粥样硬化,REVERSAL,评价与普伐他汀,(40mg/ d),比较,强化降脂,(,阿托伐他汀,80mg/d),可否阻止或逆转冠状动脉斑块,用,IVUS,定量评估整个冠状动脉斑块总体积,(TPV),在干预前后的,18,个月的变化百分率,强化降脂逆转动脉粥样硬化 REVERSAL,REVERSAL,Nissen SE. JAMA. 2004;291: 1071-1080,REVERSALNissen SE. JAMA. 2004;,REVERSAL,Nissen SE. JAMA. 2004;291: 1071-1080,与普伐他汀,40mg,组的斑块进展相比，立普妥,80mg,组的斑块进展显著减慢。,但与基线相比，斑块进展无显著差异。,REVERSALNissen SE. JAMA. 2004;,舒降之治疗逆转冠状动脉粥样硬化,- IVUS,研究,用,IVUS,观察基线,3,个月低脂饮食后,舒降之,40mg,进行再,12,个月治疗后,舒降之,40mg,，增加到,80mg (,如果,1,或,3,个月的,40mg,治疗不能使,TC5.0mmol/dl,、,LDL-C130mg/dl,胸动脉斑块,4.0mm,颈动脉斑块,2.0mm,MRI,观察舒降之,40mg,在基线和每,6,个月时患者的斑块变化,共,2,年,与基线相比,18,个月,24,个月,主动脉损伤,血管壁面积,-13%,-16%,最大血管厚度,-12%,-16%,颈动脉损伤,血管壁面积,-16%,-18%,最大血管厚度,-15%,-19%,主动脉,内腔面积,+5%,+6%,颈动脉,内腔面积,+ 4%,+ 5%,Lipid Lowering by Simvastatin Induces Regression of Human Atherosclerotic Lesions. (Two Years Follow-Up by High-Resolution Noninvasive Magnetic Resonance Imaging) , Roberto Corti, MD. Circulation. 2002; 106: 2884-2887),P0.001,舒降之降脂治疗促使动脉粥样斑块逆转(高分辨率,非侵入性M,舒降之,降脂治疗促使动脉粥样斑块逆转,(,高分辨率,非侵入性,MRI,的,2,年随访,),研究,Circulation 2002; 106: 2884-2887,n=21,血浆脂质水平,(mg/dl),时间（周）,血浆脂质水平时间变化折线图,TC,LDL-C,HDL-C,舒降之降脂治疗促使动脉粥样斑块逆转(高分辨率,非侵入性M,153,例家族性高胆固醇血症的患者接受舒降之,80mg,治疗,2,年，观察颈动脉与股动脉,IMT(,内膜,-,中膜厚度,),的变化,Arch Intern Med(163)1837-1841,-44.4%,ASAP,的后续研究：大剂量舒降之,(80mg),的,IMT,消退研究,Arch Intern Med(163)1837-1841-,ASAP,的后续研究：大剂量舒降之,(80mg),的,IMT,消退研究,P0.001,Pernette R et al.Arch Intern Med(163)1837-1841,P0.001,P0.001,ASAP的后续研究：大剂量舒降之(80mg)的IMT消退研,舒降之治疗的重要性,因为,AMI,而实施过,PCI,的缺血性心衰患者,202,名因,AMI(,左室射血分数,50%,和择期进行血管再通术的患者,随访,12,个月,12,个月后,舒降之组支架外周斑块显著逆转，非支架处中间斑块显著逆转，主要危险事件显著减少,Simvastatin does not inhibit intimal hyperplasia and restenosis but promotes plaque regression in normocholesterolemic patients undergoing coronary stenting: A randomized study with intravascular ultrasound; Am Heart Journal 2005; 149: 520-6,舒降之促进冠脉支架术患者的斑块逆转IVUS随机研究比较辛,舒降之促进冠脉支架术患者的斑块逆转,IVUS,随机研究,MLA:,最小支架处内腔面积,; IHV:,内皮增生体积,; IH:,内皮增生,; PSPV:,支架外周斑块体积,; PSP:,支架外周斑块,; NSPV:,非支架处斑块体积,; NSP:,非支架处斑块,Simvastatin does not inhibit intimal hyperplasia and restenosis but promotes plaque regression in normocholesterolemic patients undergoing coronary stenting: A randomized study with intravascular ultrasound; Am Heart Journal 2005; 149: 520-6,舒降之促进冠脉支架术患者的斑块逆转IVUS随机研究MLA,舒降之促进冠脉支架术患者的斑块逆转,IVUS,随机研究,由舒降之治疗导致的斑块逆转不能仅仅通过降脂作用来解释，事实上本项研究的入选患者血脂水平趋于正常,通过治疗,他们的总胆固醇和,LDL-C,没有极大幅度的降低,生物多样性的作用是与辛伐他汀分子的特异性有关,舒降之除了降脂作用,还有很多生物多样性,如保护内皮功能、抗炎作用、抑制平滑肌细胞增生等,其它研究证明药物支架对于术前已经存在于支架外周的动脉粥样斑块没有明显作用,Simvastatin does not inhibit intimal hyperplasia and restenosis but promotes plaque regression in normocholesterolemic patients undergoing coronary stenting: A randomized study with intravascular ultrasound; Am Heart Journal 2005; 149: 520-6,舒降之促进冠脉支架术患者的斑块逆转IVUS随机研究由舒降,全面调脂策略,降低,LDL-C,、,TG,、,LP(a) +,升高,HDL-C,Simvastatin does not inhibit intimal hyperplasia and restenosis but promotes plaque regression in normocholesterolemic patients undergoing coronary stenting: A randomized study with intravascular ultrasound; Am Heart Journal 2005; 149: 520-6, 全面调脂策略Simvastatin does,HDL,抑制动脉粥样硬化斑块进展,黏附分子,单核细胞,内膜,血管腔,内皮细胞,LDL,LDL,MCP-1,巨噬细胞,细胞因子,泡沫细胞,HDL,促进胆固醇逆向转运,被修饰的,LDL,HDL,抑制,LDL,的氧化,HDL,抑制黏附因子的表达,HDL抑制动脉粥样硬化斑块进展黏附分子单核细胞内膜血管腔内皮,全面调脂,TG,、,HDL-C,、,Lp(a),是心血管疾病重要危险因素,HDL-C,每增加,1mg/dl,，心血管事件降低,2%3%,，烟酸和贝特类药,物均可增加,HDL-C,，烟酸更显著,部分他汀虽然轻度增高,HDL-C,，但大剂量他汀并不能使,HDL-C,进,一步增加,早期烟酸作为降脂药副作用大，随着烟酸剂型改进和烟酸衍生物的,出现，因具有增加,HDL-C,和降低,TG,的作用而日益受到重视,Simvastatin does not inhibit intimal hyperplasia and restenosis but promotes plaque regression in normocholesterolemic patients undergoing coronary stenting: A randomized study with intravascular ultrasound; Am Heart Journal 2005; 149: 520-6,全面调脂 TG、HDL-C、Lp(a)是心血管疾病重要,舒降之,40mg:,全面强效针对各主要血脂参数,在心脏保护研究中的,4-6,周的随机分组前期，每,3,位患者中就有,1,位，,其,LDL-C,下降达,48%,或更多,1.,心脏保护研究小组,柳叶刀,2002; 360:7-22,2.,数据资料默沙东公司提供,3.,美国心脏病学杂志,1999;83:1476-1477,4.,美国心脏病学杂志,1998;82:311-316,LDL-C,下降达,-48%,*,1,HDL-C,上升达,+13%,2,3,TG,下降达,-32%,4,舒降之40mg:全面强效针对各主要血脂参数 在心脏保护研究,等效剂量,n=99,+8%,+4%,当代治疗研究,2001;62(5):408-415,舒降之,升高,HDL-C,优于,阿托伐他汀,研究设计,*,常用剂量研究,:,一个为期,2-6,个月研究,评估舒降之,及阿托伐他汀对于采取严格低脂饮食治疗但甘油三酯仍未得以良好控制的高胆固醇血症患者,(,没有服用降脂药物,总胆固醇,250mg/dL),的降甘油三酯作用,.,患者被随机分配舒降之,20mg/,天,(n=100),或阿托伐他汀,10mg/,天,(n=99),治疗,6,个月,.,在基线,2,个月及,6,个月时,分别检测血甘油三酯,总胆固醇, LDL-C,及,HDL-C.,10,5,0,n=100,舒降之,20mg,阿托伐他汀,10mg,等效剂量n=99+8%+4%当代治疗研究 2001;62(5,全面调脂,烟酸降低,TC15%30%,、,LDL-C5%25%,、,TG20%50%,、,LP(a) 20%30%,，升高,HDL-C15%35%,目前是唯一降低,LP(a),的调脂药物,改变,HDL-C,亚组分：提高,HDL-C2/HDL-C3,比例，增加,APOA1/APOAII,，增加,HDL,体积，减小,HDL,密度,Simvastatin does not inhibit intimal hyperplasia and restenosis but promotes plaque regression in normocholesterolemic patients undergoing coronary stenting: A randomized study with intravascular ultrasound; Am Heart Journal 2005; 149: 520-6,全面调脂 烟酸降低TC15%30%、LDL-C5%25,全面调脂,三类调脂药对血脂的影响,HDL-C,（,-,）,TG,（,-,）,HDL-C,（,+,）,LP(a),（,-,）,烟酸类,5%25% 20%50% 15%35% 20%30%,他汀类,18%55% 7%30% 5%15%,贝特类,5%20% 20%50% 10%20%,Simvastatin does not inhibit intimal hyperplasia and restenosis but promotes plaque regression in normocholesterolemic patients undergoing coronary stenting: A randomized study with intravascular ultrasound; Am Heart Journal 2005; 149: 520-6,全面调脂 三类调脂药对血脂的影响Simvastatin,全面调脂,依折麦布（,1000mg)+,辛伐他汀（,10mg),LDL-C,下降,44%,相当于辛伐他汀（,80mg),依折麦布（,1000mg)+,阿托伐他汀（,10mg),LDL-C,下降,50%,相当于阿托伐他汀（,80mg),Simvastatin does not inhibit intimal hyperplasia and restenosis but promotes plaque regression in normocholesterolemic patients undergoing coronary stenting: A randomized study with intravascular ultrasound; Am Heart Journal 2005; 149: 520-6,全面调脂 依折麦布（1000mg)+辛伐他汀（10mg),全面调脂,他汀与烟酸类合用，获得协同或增强的调脂效果,他汀类药物相关不良事件荟萃分析（,2006Clinical Therapeutics),：他汀降低心血管事件的风险达,26%,（,P0.01,），同时增加不良事件的风险达,39%,，若对高危患者采用强化降脂使,LDL-C,降至,80mg,以下，在增加他汀剂量的同时不良反应随之增多,烟酸与他汀联用可进一步降低,LDL-C,，且在降低,TG,、升高,HDL-C,方面强于他汀,Simvastatin does not inhibit intimal hyperplasia and restenosis but promotes plaque regression in normocholesterolemic patients undergoing coronary stenting: A randomized study with intravascular ultrasound; Am Heart Journal 2005; 149: 520-6,全面调脂 Simvastatin does not,全面调脂,目前缓释型烟酸（,1000mg),和洛伐他汀（,40mg,）的复方降脂药已,获,FDA,比准上市,近期研究复合制剂在全面改善血脂谱方面优于他汀，且联合用药的,肝损害、肌病等发生率与单用他汀相似，其安全性、耐受性较好,他汀与烟酸合用发生肌病的危险低于他汀联用贝特,Simvastatin does not inhibit intimal hyperplasia and restenosis but promotes plaque regression in normocholesterolemic patients undergoing coronary stenting: A randomized study with intravascular ultrasound; Am Heart Journal 2005; 149: 520-6,全面调脂 目前缓释型烟酸（1000mg)和洛伐他汀（4,THANK,YOU,THANK,