他汀对不稳定斑块的作用_张沛.ppt
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1、他汀对不稳定斑块的作用,阜外心血管病医院 张 沛,TCC 2009,CRP=C反应蛋白;; LDL-C=低密度脂蛋白胆固醇. Libby P. Circulation. 2001;104:365-372; Ross R. N Engl J Med. 1999;340:115-126.,单核细胞,LDL-C,黏附分子,巨噬细胞,泡沫细胞,氧化的 LDL-C,斑块破裂,平滑肌细胞,CRP,“LDL-C斑块事件”链 动脉粥样硬化性疾病的共同发病机制,事件,动脉粥样硬化的主要分型 I,动脉粥样硬化的主要分型 II,Atherosclerosis and the Arterial Wall,From S
2、tary HC. Atlas of Atherosclerosis: Progression and Regression. 2nd ed. New York: Parthenon Publishing; 2003, used with permission. Insull W Jr. Am J Med. 2009;122:S3S14.,Lumen,Lipid-Rich Necrotic Core,Fibrous Cap Atheroma,Normal,Media,Adventitia,Intima,Developmental Pathology of Arterial Lesions,Thi
3、n fibrous cap atheroma. From Virmani R et al. Arterioscler Thromb Vasc Biol. 2000;20:1262-1275; used with permission.,Healed plaque rupture. From Stary HC. Atlas of Atherosclerosis: Progression and Regression. 2nd ed. New York: Parthenon Publishing; 2003; used with permission.,Stenosis (cross sectio
4、n of anterior descending coronary artery). From Stary HC. Atlas of Atherosclerosis: Progression and Regression. 2nd ed. New York: Parthenon Publishing; 2003; used with permission.,Thin fibrous cap,Lipid-rich necrotic core,See Figure 3 for developmental flow chart.,Older fibrous cap,Newer fibrous cap
5、,Insull W Jr. Am J Med. 2009;122:S3S14.,Increasing Extent of Atherosclerotic Plaques With Age,CVD = cardiovascular disease; LAD = left anterior descending coronary artery. Adapted with permission from McGill HC Jr (ed). Lab Invest. 1968;18:465653. Insull W Jr. Am J Med. 2009;122:S3S14.,Age Group (Ye
6、ars),Mean Percent Intimal Surface Involved With Lesions,Atherosclerosis in LAD White Males New Orleans High Risk of CVD,Atherosclerosis in LAD White Males Santiago, Chile Low Risk of CVD,Age Group (Years),导致急性冠脉综合症的主要粥样斑块类型,Rupture of the thin cap fibrous atheroma (TCFA) Erosion of the endothelium P
7、rotrusion of a calcified nodule into the arterial lumen Advanced stenosis of fibrocalcific plaque,Developmental Pathology of Atherosclerosis,ACS = acute coronary syndromes. Adapted with permission from Virmani R et al. Arterioscler Thromb Vasc Biol. 2000;20:12621275. Insull W Jr. Am J Med. 2009;122:
8、S3S14.,Adapted from Rosensen RS. Exp Opin Emerg Drugs 2004;9(2):269-279 LaRosa JC et al. N Engl J Med 2005;352:1425-1435,他汀类药物试验中,LDL-C 治疗和冠心病密切相关 - 低些好些,他汀疗效机制的多样性,降低 LDL-C和心血管事件的风险 减小斑块体积 改变斑块细胞成分 改变斑块化学成分 改变斑块以炎症和胆固醇代谢为核心的生物活性,核心:稳定和逆转斑块,4项他汀安慰剂对比治疗颈动脉内膜切除 组织病理汇萃分析,LDL-C平均降至90mg/dL 巨噬细胞 57% 淋巴细胞
9、67% 总脂质 72% 蛋白溶解酶:MMP-2 68%、MMP-9 73% COX-2 enzymes 胶原 160% 平滑肌细胞 ,他汀稳定ACS患者不稳定斑块的临床研究,“立普妥组斑块高回声的变化意味着斑块组成的改变, 而这种改变可能减少斑块破裂的风险.”,Schartle M, Circulation. 2001;104:387-392.,GAIN:立普妥 20-80mg/d 稳定冠脉斑块,German Atorvastatin Intravascular Ultrasound Study Investigators (GAIN),MIRACL 主要结果,0,4,8,12,16,15,1
10、0,5,0,累积发生率 (%),从随机化分组起的时间 (周),阿托伐他汀80mg,安慰剂,17.4%,14.8%,降低风险 = 16% p=0.048,到首次发生各终点事件的时间:,95% CI = 0.7010.999,死亡 (任何原因) 非致死性心梗 复苏的心脏停搏 有新客观心肌缺血证据的恶化心绞痛,需要紧急再次住院治疗,MIRACL Investigators JAMA 2001;285:1711-1718.,Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL),随机、双盲研究 入选病例共4
11、,162例 - ACS发生10天内、 TC 240mg/dL(在用降脂药物治疗者TC 200mg/dL ),阿司匹林 + 常规药物治疗,标准治疗 普伐他汀 40 mg, qd,强化治疗 阿托伐他汀 80 mg, qd,加替沙星,加替沙星,安慰剂,安慰剂,研究时间: 平均2年随访期 (1,001 事件),主要终点:死亡、心梗、不稳定心绞痛需要住院、 需行血管再建术 (随机入选后 30天)、或中风,PROVE-IT:第一个比较两种他汀类治疗方案在ACS人群中应用的临床研究,事件%,随访月数,普伐他汀 40mg (26.3%),阿托伐他汀 80mg (22.4%),16% RRR (2年) (p =
12、 0.005),30,25,20,15,10,5,0,PROVE-IT 主要终点结果,Cannon CP et al. N Engl J Med 2004;350,16%,a hazard risk reduction of 24% (HR 0.76; 95% CI, 0.66 to 0.88; p 0.0002),回顾分析:以死亡、心梗、不稳定心绞痛需要住院、 需行血管再建术为复合终点,HR 0.81; 95% CI, 0.65 to 0.98; p 0.03 * HR 0.72; 95% CI, 0.52 to 0.99; p 0.046 #,*,#,stable patients who
13、 were free of clinical events at six months showed a similar benefit in favor of intensive statin therapy (atorvastatin, 80mg),ARMYDA-RECAPTURE (Atorvastatin for Reduction of MYocardial Damage during Angioplasty trial 阿托伐他汀降低血管成形术中心肌损伤研究) 前瞻性、多中心、随机、双盲研究,观察长期他汀治疗的患者接受PCI治疗时再次负荷量阿托伐他汀的疗效,5,18,P=0.025
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