《他汀对不稳定斑块的作用》由会员分享，可在线阅读，更多相关《他汀对不稳定斑块的作用（46页珍藏版）》请在金锄头文库上搜索。
1、他汀对不稳定斑块的作用阜外心血管病医院张 沛TCC 2009CRP=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斑块不稳定 和血栓形成斑块形成炎症/氧化内皮功能受损“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 IIAtherosclerosis and the Arterial Wal
2、lFrom Stary 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.LumenLipid-Rich Necrotic CoreFibrous Cap Atheroma NormalMediaAdventitiaIntimaDevelopmental Pathology of Arterial LesionsThin
3、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 section o
4、f 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 capThin fibrous capLipid-rich necrotic coreLipid-rich necrotic coreSee Figure 3 for developmental flow chart.Ol
5、der Older fibrous fibrous capcapNewer Newer fibrous fibrous capcapInsull W Jr. Am J Med. 2009;122:S3S14.Increasing Extent of Atherosclerotic Plaques With AgeCVD = cardiovascular disease; LAD = left anterior descending coronary artery. Adapted with permission from McGill HC Jr (ed). Lab Invest. 1968;
6、18:465653. Insull W Jr. Am J Med. 2009;122:S3S14.Age Group (Years)Mean Percent Intimal Surface Involved With LesionsAtherosclerosis in LAD White Males New Orleans High Risk of CVDAtherosclerosis in LAD White Males Santiago, Chile Low Risk of CVDAge Group (Years)导致急性冠脉综合症的主要粥样斑块类型nRupture of the thin
7、 cap fibrous atheroma (TCFA)nErosion of the endotheliumnProtrusion of a calcified nodule into the arterial lumennAdvanced stenosis of fibrocalcific plaqueDevelopmental Pathology of AtherosclerosisACS = acute coronary syndromes. Adapted with permission from Virmani R et al. Arterioscler Thromb Vasc B
8、iol. 2000;20:12621275. Insull W Jr. Am J Med. 2009;122: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 - 低些好些治疗后的 LDL-C 水平 mg/dL (mmol/L)WOSCOPS 安慰剂ASCOT - 安慰剂AFCAPS - RxWOSCOPS - RxASCOT - Rx4S - RxHPS
9、- 安慰剂LIPID - Rx4S 安慰剂CARE - RxLIPID - 安慰剂 CARE - 安慰剂HPS - Rx05101520253040 (1.0)60 (1.6)80 (2.1)100 (2.6)120 (3.1)140 (3.6)160 (4.1)180 (4.7)事件发生率 (%)6二级预防一级预防Rx 他汀类治疗 PRA 普伐他汀 ATV 阿托伐他汀200 (5.2)PROVE-IT - PRA PROVE-IT ATVTNT ATV10TNT ATV80 AFCAPS - 安慰剂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
10、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 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 稳定冠脉斑块高回声指数变化
11、百分比 (%)立普妥组常规治疗组01020304050 42%10%立普妥组： LDL-C，155 86mg/dL常规治疗组：LDL-C，166 140mg/dLGerman Atorvastatin Intravascular Ultrasound Study Investigators (GAIN)MIRACL 主要结果0481216151050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 w死亡 (任何原因)w非致死性心梗w复苏的心脏停搏w有
12、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4,162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,
13、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0 03 3181821212424272730306 69 912121515事件事件%随访月数普伐他汀普伐他汀 40mg40mg (26.3%)(26.3%)阿托伐他汀阿托伐他汀 80mg80mg (22.4%)(22.4%)16% RRR 16% RRR （2 2年）年） (p = 0.005)(p = 0.005)303025252020151510105 50 0PROVE-IT 主要终点结果Cannon
14、 CP et al. N Cannon CP et al. N EnglEngl J Med 2004;350 J Med 2004;35016%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 were free of clini
15、cal 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术中心肌损伤损伤 研究)前瞻性、多中心、随机、双盲研究，观观察长长期他汀治疗疗的患 者接受PCI治疗时疗时 再次负负荷量阿托伐他汀的疗疗效518P=0.025MI (%)PlaceboAtorvastatinPasceri V, Di Sciascio G, et al. Circulation 2004 ARMYDA-RECAPTURE背景 (未服用他汀的患者)ARMYDA trial517P=0.01MACE (%)PlaceboAtorvastatinARMYDA-ACS trialPatti G, Di Sciascio G, et al. J Am Coll Cardiol 2007ARMYDA-RECAPTURE : 研究设计设计793 名 接受冠脉造影的 稳稳定心绞绞痛或 NSTE-ACS患者造影前12小时时
