急性冠脉综合征的抗栓治疗策略 北京安贞医院　　 周玉杰

急性冠状动脉综合征定义 (Acute Coronary Syndrome, ACS) 冠状动脉粥样硬化斑块破裂(rupture)或糜烂(erosion)，继发完全或不完全闭塞性血栓形成为病理基础的一组临床综合征 根据心电图表现分为ST段抬高型（STE-ACS）和非ST段抬高型（NSTE-ACS）

ACS的分类

急性冠脉综合征 动脉粥样硬化疾病的“冰山一角”

CVD: An increasing problem 16.6 million people die every year from cardiovascular disease1 CVD 1/3 of global deaths By 2010, leading cause of death in developing countries By 2020, 25 million deaths worldwide 1WHOwww.who.int/whosis/

急性冠状动脉综合征的流行病学 据流调资料显示我国急性冠脉综合征的年发病率为50/100,000人，而且这一数字正在逐年增加

在我国心脏疾病已超越恶性肿瘤成为首要死亡原因 N Engl J Med 2005;353:1124-34

我国冠心病年死亡率接近100/100,000人 N Engl J Med 2005;353:1124-34

Clinical Presentations of Coronary Disease Vulnerable Plaque “ Active Volcano” Thrombotic effect ACS Calcified Plaque “ Dormant Volcano ” Hemodynamic effect Stable Angina

STE-MI和NSTE-ACS病理

Soft or ‘Vulnerable’ Plaque Imaging by 64 slice MSCT

DRUG ELUTNG STENTS to eliminate the need for CABG operations ?

SEM showed > 95% endothelized Uncovered stent strut (F, arrow). FIM Study: Vascular Healing 4-Year after SES Implantation (Pathological Findings) Dante Pazzanese F Pt # 4 (Fast release) SEM showed > 95% endothelized stent surface (F, G). Uncovered stent strut (F, arrow). G Courtesy of R. Virmani

NSTE-ACS

NSTE-ACS 抗血小板治疗 １．阿司匹林 环氧化酶１（COX-1）抑制剂 ２．噻氯吡定类，包括氯吡格雷和抵克力得　二磷酸腺苷（ADP）受体拮抗剂 ３．糖蛋白（GP）IIb/IIIa受体拮抗剂，包括阿昔单抗、依替巴肽和替洛非班

抗血小板治疗的作用机制 JAMA. 2004;292:1875-1882

2004年ACCP7推荐的抗血小板治疗 JAMA. 2004;292:1875-1882

Aspirin History (From the German acetylspirsaure + chemical suffix – in) First synthesized in pure form by Felix Hoffman of Friedr. Bayer & Co. in 1897.

First pill in USA was 5 grains (~325 mg). Aspirin History Due to problems with the original Aspirin powder being counterfeited, it became the first pharmaceutical agent ever sold in pill form in early 1900’s. First pill in USA was 5 grains (~325 mg).

阿司匹林 对于所有没有明确阿司匹林过敏的 NSTE ACS患者，推荐立即口服阿司匹林300mg，随后每日口服100mg 阿司匹林过敏或胃肠道疾患不能耐受的患者，应当使用氯吡格雷

Metabolic Pathways of Arachadonic Acid Membrane Phospholipids ARACHIDONIC ACID Aspirin COX-1 Prostaglandin H2 Thromboxane A2  Platelet Aggregation Vasoconstriction Prostacyclin  Platelet Aggregation Vasodilitation

Aspirin in the Treatment of ACS 0.00 0.05 0.10 0.15 0.20 0.25 Placebo Probability of Death or MI Aspirin 75 mg Risk ratio 0.52 95% CL 0.37-0.72 3 6 9 12 Months Wallentin LC, et al. JACC 1991;18:1587-93.

What is “Aspirin Resistance?” Inability of ASA to prevent treated patients from having thrombotic events. Patrono C. J Thromb Haemost 2003;1:1710-3

Aspirin Resistant Patient Management   Eliminate interfering substances (ibuprofen) Increase aspirin dose Use other anti-platelet medications such as clopidogrel to prevent recurrent ischemic events Educate patient on importance of compliance It is very important to the physician that something can be done for the patient as a result of determining that a patient is a non-responder to aspirin therapy. In this case there are several courses of action that can address the problem, including: Determining that the patient is actually taking their aspirin regularly. Surprisingly, even though aspirin has profound benefits, many patients do not always take their aspirin. Once a patient is found to be a non-responder, most will admit to the doctor that they may not have been compliant, which serves as an key way to reinforce the importance and reinitiate consistent therapy. There many other medications that can interfere with the effectiveness of aspirin therapy that need to be changed or eliminated to ensure that a patient is receiving the full benefit of aspirin therapy. One very common medication, ibuprofen, the active ingredient in Advil, Motrin and other commonly used pain relievers, interferes with aspirin. Changing the type of pain reliever used, can eliminate this source of interference with aspirin effectiveness. Even though it is desirable to use the lowest possible dose of aspirin to minimize bleeding risk, often times the standard 81 mg dose of aspirin is not sufficient to produce the desired antiplatelet effects. In many cases, simply increasing the dose can produce that effect. Lastly, there is Plavix therapy. If a patient does not respond to aspirin, the alternative of choice is Plavix. However, because Plavix at $3 per table is considerably more expensive than aspirin, it is important to first determine if aspirin is working.

Conclusions ASA use associated with 23% reduction in the odds of vascular events ASA resistance 5-60% ASA resistance associated with increased risk of major adverse cardiovascular events

阿司匹林降低急性冠脉综合征患者心梗和死亡的发生 80 ASA=75毫克 N=796 70 60 50 40 Q波心梗和死亡发生率的降低（%） 30 对796名发作过急性冠脉综合征（包括非Q波心肌梗死和不稳定型心绞痛）的男性患者，评估了小剂量阿司匹林75毫克/天对其Q波心肌梗死的发病率以及死亡率的影响。这些患者被随机分配到安慰剂对照组以及阿司匹林治疗组和/或静脉内注射肝素5天的治疗组内，主要终点为心肌梗死或死亡。结果显示：小剂量ASA的治疗将患有不稳定型冠状动脉疾病的男性患者在疾病发作后的第5、30和90天时的发生心肌梗死或死亡的危险性分别降低了57％、69％和64％。P值均小于0.05。 20 10 5 30 90 距离治疗开始的时间（天） Lancet 1990;336:827–30

氯吡格雷 对于所有没有明确阿司匹林过敏的 NSTE ACS患者，推荐立即口服氯吡格雷300 mg，随后75 mg/日 对于不能马上进行诊断性导管术或冠脉造影后不能在5天内行CABG术的NSTE-ACS患者，推荐立即口服氯吡格雷300 mg，随后每日75 mg至9到12个月，同时合用阿司匹林 对于正在服用氯吡格雷并准备接受CABG手术的患者，推荐术前５日停用氯吡格雷

抵克力得 抵克力得由于其粒细胞减少等并发症多，临床上已渐被氯吡格雷所替代 抵克力得的适应症与氯吡格雷大致相同，首剂口服500mg，随后250mg每日２次

CURE试验的目的是为了研究在阿司匹林治疗的基础上再阻断ADP途径所引起的血小板聚集是否可获益。该试验入选12562例UA/NSTEMI病人，在24小时内随机分组用安慰剂和氯吡格雷（负荷剂量300mg，然后每天75mg）治疗，然后随访3～12个月，所有病人均给以阿司匹林。联合终点事件（心血管死亡、心肌梗死、或卒中）发生率，安慰剂组为11.5%，氯吡格雷组为9.39%（RR0.80，P＜0.001）。

PCI-CURE为CURE试验的亚组研究，入选2658例病人，随机、双盲分为安慰剂组（n=1345）和氯吡格雷组（n=1313）所有病人均给以阿司匹林。入选病人在行冠状动脉介入（PCI）治疗前平均10天接受安慰剂或氯吡格雷，术后大多数病人接受开放标签药物（氯吡格雷或抵克立得）治疗2～4周，之后再使用研究药物8个月。初级终点（联合心血管死亡、心肌梗死、或紧急靶血管血运重建）安慰剂组为86例（6.4%），氯吡格雷组为59例（4.5%，RR0.7，P=0.03）。氯吡格雷组心血管死亡、心肌梗死事件发生率下降了31%。

GP Ⅱb/Ⅲa受体拮抗剂 对于中高危的NSTE-ACS患者，推荐早期应用依替巴肽或替洛非班，同时合用阿司匹林和普通肝素

GPIIb/IIIa受体拮抗剂临床研究

GPIIb/IIIa受体拮抗剂在PCI中的应用 30 天死亡 试验 N OR & 95% CI 安慰剂 IIb/IIIa EPIC 2099 1.7% 1.5% EPILOG 4891 1.2% 0.9% RAPPORT 5374 1.3% 1.0% CAPTURE 6639 1.3% 1.0% IMPACT I 6789 1.3% 1.0% IMPACT II 10,799 1.2% 0.9% RESTORE 12,940 1.1% 0.9% EPISTENT 15,339 1.1% 0.8% Kong D, et al. Am J Cardiol. 2003; 92:651-655 This slide demonstrates all of the trials to date that have studied GP IIb/IIIa inhibitors in patients undergoing PCI, and includes MI trials as well. With respect to mortality, a 27% survival benefit has been demonstrated with the use of GP IIb/IIIa inhibitors.1 1. Kong D, Hasselblad V, Harrington R, White H, Tcheng J, Kandzari D, Topol E, Califf R. Meta-analysis of survival with platelet glycoprotein IIb/IIIa antagonists for percutaneous coronary intervention. Am J Cardiol. 2003;92:651-655. ESPRIT 17,403 1.0% 0.8% ISAR-2 17,804 1.1% 0.8% ADMIRAL 18,104 1.2% 0.8% 0.73 (0.55, 0.96) P=0.024 CADILLAC 20,186 1.3% 0.9% 0.1 1 10 IIb/IIIa 较好 安慰剂较好

GPIIb/IIIa受体拮抗剂在PCI中的应用 30 天死亡/心梗 38% (P <0.00000001) 试验名称 N 危险比 & 95% CI 安慰剂 IIb/IIIa¯ 2,099 9.6% 6.6% EPIC IMPACT-II 4,010 8.5% 7.0% EPILOG 2,792 9.1% 4.0% CAPTURE 1,265 9.0% 4.8% RESTORE 2,141 6.3% 5.1% EPISTENT 2,399 10.2% 5.2% ESPRIT 2,064 10.2% 6.3% 汇总分析 汇总 16,770 0.62 (0.55, 0.71) p < 0.000000001 8.8% 5.6% 0.5 1 1.5 2 IIb/IIIa 拮抗剂更好 安慰剂更好

GPIIb/IIIa受体拮抗剂在ACS中的应用 30 天死亡/心梗 9% (P=0.015) Study Placebo IV Gp IIb/IIIa O R 95% CI PRISM 7.1% 5.8%* 0.80 0.60-1.06 PRISM-PLUS 12.0% (*) 8.7% 0.70 0.50-0.98 († ) 13.6%* 1.17 0.80-1.70 PARAGON-A 11.7% (l) 10.3% 0.87 0.58-1.29 (h) 12.3% 1.06 0.72-1.55 PURSUIT 15.7% (l) 13.4% 0.83 0.70-0.99 (h) 14.2% 0.89 0.79-1.00 PARAGON-B 11.4% 10.6% 0.92 0.77-1.09 GUSTO-IV 8.0% (24h) 8.2% 1.02 0.83-1.24 (48h) 9.1% 1.15 0.94-1.39 Overall 11.8% 10.8%t 0.91 0.85-0.98 1.0 2.0 Gp IIb/IIIa Better Placebo Better P=.015 * Without heparin. † With/without heparin. (l), Low dose; (h), High-dose. Boersma E, et al. Lancet. 2002;359:189-198. References Boersma, E. et al. Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a meta-analysis of all major randomized clinical trials. Lancet. 2002;359:189-198.

9%

替洛非班的用法 起始30分钟内，静脉输注0.4μg/kg/min，随后0.1μg/kg/min维持至少48小时；应与肝素联用，维持APTT在正常的1.5-2.0倍或ACT在200-250秒；或与低分子肝素联用 严重肾功能不全（血清肌酐清除率<30ml）的患者应用时剂量减少50%

替洛非班的不良反应和禁忌症 不良反应 出血和血小板减少 禁忌症 对替洛非班过敏者 活动性内出血患者 　　出血和血小板减少 禁忌症 对替洛非班过敏者 活动性内出血患者 颅内出血史、颅内肿瘤、动静脉畸形及动脉瘤患者 曾应用替洛非班造成血小板减少的患者

NSTE-ACS 抗凝治疗 １．普通肝素 ２．低分子肝素 ３．选择性间接抗Xa因子抑制剂：人工合成戊糖 ４．凝血酶直接抑制剂（Direct thrombin inhibitors, DTI）

凝血机制 组织损伤 XIIa XIa VIIa IX IXa vWF +VIII TFPI TFPI Xa X X Va TFPI 凝血过程复杂，许多机制参与血栓的形成 组织损伤 XIIa XIa VIIa 组织因子 IX IXa vWF +VIII TFPI TFPI Xa X X Va TFPI II (prothrombin) IIa (thrombin) XIII I (fibrinogen) Fibrin Thrombus Thromb Haemost 1999;82:165-74 N Engl J Med 1997;337:688-98

普通肝素 Unfractionated Heparin (UFH) 对于NSTE-ACS患者，推荐短期（48小时）普通肝素与抗血小板治疗联合应用；普通肝素的初始剂量最好应根据公斤体重调整

抗血小板与短期普通肝素联合治疗降低２周内NSTE-ACS患者的死亡和心梗率 Circulation 1994;89:81-88

普通肝素的用法 固定剂量：负荷量5000U静注，随后1000U/小时持续静注，将aPTT维持于50到75秒或正常值的1.5-2.5倍（ACT 200-300秒） 按体重调节：负荷量60-70U/kg（最大5000U ），随后12-15U/kg/小时（最大1000U/小时），将aPTT维持于50到75秒或正常值的1.5-2.5倍 （ACT 200-300秒）

低分子肝素 Low-Molecular-Weight Heparin (LMWH) 对于NSTE-ACS患者，推荐应用低分子肝素替代普通肝素 对于已经接受了低分子肝素抗凝的NSTE-ACS的患者，建议在PCI术中继续应用低分子肝素抗凝

低分子肝素与普通肝素 低分子肝素 2:1 - 4:1 长 固定 高 无需 低 小 普通肝素 1:1 短 不固定 低 需要 高 大 抗 Xa:IIa 活性比值 血浆半衰期 清除率 生物利用度 需 APTT 监测 对 PF4 的敏感性 对血小板抑制作用 25

低分子肝素的优势 疗效方面： 比小剂量肝素抗凝效果更好 可以预计的临床效果 固定剂量 良好的药代动力学（半衰期长，可每日一至两次给药） 抗因子 Xa作用较抗凝血酶 （IIa) 作用强 安全性方面： 出血的风险减少 血小板减少症发生减少 由于对血小板聚集的影响减少，对最初的止血影响减少。

LMWH与UFH相比减少NSTE-ACS患者30日死亡及心梗率 JAMA 2004;292:89-96

LMWH的用法 ih Q12h 推荐疗程7-14日 必要时可监测血浆抗Xa因子活性 严重肾功能不全（血清肌酐清除率<30ml/h）者需使用时可每日1次

UFH 和LMWH的不良反应和禁忌症 不良反应 出血和血小板减少 禁忌症 对UFH 和LMWH过敏 严重凝血功能障碍 　出血和血小板减少 禁忌症 对UFH 和LMWH过敏 严重凝血功能障碍 有肝素诱导的血小板减少症史 活动性消化道溃疡或有出血倾向的器官损伤 急性感染性心内膜炎

选择性间接抗Xa因子抑制剂：人工合成戊糖（Fondaparinux） 在OASIS-5研究中fondaparinux在ACS后9天内在预防心血管事件、死亡和缺血发作方面同enoxaparin一样有效(5.9% vs 5.8%, HR 1.01)，并且显著降低严重出血并发症(3.2% vs 7.0%, HR 0.44, p<0.001)。研究显示fondaparinux明显降低ACS事件后1个月内的死亡率(2.9% vs 3.5%, p=0.022)，在6个月的随访期内同样有效(5.6% vs 6.3%, HR 0.89, p=0.037) ESC 2005

凝血酶直接抑制剂 对于NSTE-ACS患者， 不推荐DTIs 作为首选抗凝治疗，除非患者出现肝素诱导的血小板减少症（heparin-induced thrombocytopenia, HIT）或既往有HIT病史

DTIs治疗NSTE-ACS的荟萃分析 Lancet 2002; 59:294–302 ＤＴｉ与普通肝素相比不能改善患者的３０日内的死亡及心梗率 Lancet 2002; 59:294–302

2005年ACC/AHA 推出UA/NSTEMI 急诊诊疗指南 Circulation. 2005;111:2699-2710

早期保守策略 阿司匹林 氯吡格雷应在急诊室尽早服用 低分子肝素或普通肝素 依替巴肽或替洛非班： 持续缺血 TnI或TnT升高 其他高危因素 5. 除非计划行进PCI，阿昔单抗不应早期使用 Circulation. 2005;111:2699-2710

早期介入策略 阿司匹林 氯吡格雷应在急诊室尽早服用 低分子肝素或普通肝素；优先使用低分子肝素 如准备早期介入干预应近尽早使用GP Ⅱb/Ⅲa受体拮抗剂，并与阿司匹林、肝素及氯吡格雷联用 如准备行PCI术，无高危出血因素者术后氯吡格雷服用12个月 与GUIDELINE相比添加了 2.氯吡格雷应在急诊室近早服用 5.无高危出血因素者术后氯吡格雷服用12个月 Circulation. 2005;111:2699-2710

STE-ACS

AMI溶栓前后的抗栓治疗 抗血小板治疗 １．阿司匹林 ２．噻氯吡定类 ３．GP Ⅱb/Ⅲa受体拮抗剂

阿司匹林 对于急性ST段抬高心梗，无论是否溶栓均推荐立即口服阿司匹林300mg，随后100mg/日

Aspirin in Acute Myocardial Infarction: ISIS-2 100 200 300 400 500 600 7 14 21 28 35 Placebo alone: 568/4300 (13.2%) Aspirin alone: 461/4295 (10.7%) Streptokinase alone: 448/4300 (10.4%) Streptokinase plus aspirin: 343/4292 (8.0%) Cumulative Number of Vascular Deaths Days From Randomization

阿司匹林降低AMI患者近期死亡、再梗及中风的机率 Data are from ISIS-2 and are for patients who were randomly assigned to receive aspirin or placebo for one month. This table should not be used to assess the effects of heparin, because heparin treatment was not randomly assigned. Just before randomly assigning each patient to aspirin or placebo, doctors were asked whether they “planned” to use intravenous heparin for that patient, and on the discharge form they reported whether they had actually done so. Deaths were recorded through the first 35 days, whereas reinfarctions, strokes, and major bleeding episodes were recorded only if they occurred before hospital discharge. Mortality percentages are based on all randomized patients (numbers given at top of columns), whereas percentages for all other events are based only on the 99 percent of patients with discharge forms. Data on heparin use include only patients discharged alive for whom discharge forms were available. IV denotes intravenous. Plus–minus values are SD. The methods used in all tables and figures to analyze the results of individual trials and to combine the results from different trials, with appropriate weight given to each trial, are described in detail elsewhere. †Of this group, 6 percent were given intravenous heparin, and a further 50 percent were given subcutaneous heparin. ‡Of this group, 77 percent were given intravenous heparin, and a further 14 percent were given subcutaneous heparin. N Engl J Med 1997; 336:847–860

氯吡格雷 对于急性ST段抬高心梗患者，无论溶栓还是介入，均建议口服氯吡格雷300mg，随后75mg/日至9-12个月

Clinical Endpoints through 30 d Odds Reduction Event Rates (%) Odds Ratio (95% CI) Clopidogrel Placebo CV Death or MI 17 8.4 9.9 Stroke 46 0.9 1.7 Recurrent ischemia leading to urgent revasc 24 3.5 4.5 CV Death, MI, or Stroke 18 9.1 10.9 CV Death, MI, Stroke, or RI  Urg Revasc 21 12.3 15.0 0.4 0.6 0.8 1.0 1.2 1.6 Clopidogrel better Placebo better N Engl J Med 2005;352:1179-1189

COMMIT: Effect of Clopidogrel on Death in Hospital Placebo + ASA: 1846 deaths (8.1%) Clopidogrel + ASA: 1728 deaths (7.5%) Dead (%) 7% (SE3) relative risk reduction (2P=0.03) Days since randomization (up to 28 days) ACC 2005

COMMIT: Effects of CLOPIDOGREL on Death, Re-MI, or Stroke by Day of Event Placebo Odds ratio & 95% CI (22,958) (22,891) Clopid. better Placebo better 463 (2.0%) 523 (2.3%) 1 486 (2.1%) 527 (2.3%) 2-3 449 (2.0%) 451 (2.0%) 4-7 432 (1.9%) 463 (2.0%) 8-28 295 (1.3%) 347 (1.5%) 9% SE 3 ALL 2125 (9.3%) 2311 (10.1%) (2P = 0.002) 0.4 0.6 0.8 1.0 1.2 1.4 1.6 ACC 2005

Bleeding Clopidogrel Placebo Type (n=22,958) (n=22,891) Cerebral Outcome Clopidogrel (%) Placebo (%) P value Through angiography TIMI major (Hgb  >5 g/dL or ICH) 1.3 1.1 NS TIMI minor (Hgb  3-5 g/dL) 1.0 0.5 Intracranial hemorrhage 0.7 Through 30 days TIMI major 1.9 1.7 In those undergoing CABG 7.5 7.2 CABG w/in 5 d of study med 9.1 7.9 TIMI minor 1.6 0.9 Clopidogrel Placebo Type (n=22,958) (n=22,891) Cerebral Fatal 39 40 Non-fatal 16 15 Non-cerebral Fatal 36 37 Non-fatal 46 36 Any major bleed 134 124 (0.58%) (0.54%)

GP Ⅱb/Ⅲa受体拮抗剂 对于急性ST段抬高心梗患者，建议任何一种GP Ⅱb/Ⅲa受体拮抗剂都不要与溶栓剂同时应用，但不包扩在急诊PCI中应用 对于急性ST段抬高心梗患者，不推荐使用GP Ⅱb/Ⅲa受体拮抗剂与半量溶栓剂及静脉低剂量普通肝素联合治疗替代标准溶栓治疗方案

GP IIb/IIIa受体拮抗剂不能降低AMI患者30日死亡率 CHEST 2004; 126:549S–575S

AMI溶栓前后的抗凝治疗 抗凝治疗 １．普通肝素 ２．低分子肝素 ３．凝血酶直接抑制剂

普通肝素 对于接受链激酶溶栓的患者，建议给予负荷量UFH 5000U静注, 随后大于80 kg者给予1000 U/h，小于80 kg者给予800 U/h抗凝治疗，监测aPTT在50到75秒之间；或皮下注射UFH 12500 U q12h 48小时

普通肝素 对于接受rt-PA、TNK-tPA及r-PA溶栓治疗的患者，推荐给予静脉UFH负荷量60U/kg（最大4000 U ），随后12 U/kg/h（最大1000 U/h）抗凝治疗48 小时；将aPTT维持于50到75秒

UFH减少AMI患者住院期间死亡、再梗及中风率 *Data are from Collins et al. This table should not be used to assess the effects of aspirin or fibrinolytic therapy, because these treatments were not randomly assigned. Deaths were generally recorded only before hospital discharge, and reinfarctions, strokes, pulmonary embolisms, and major bleeding episodes were recorded only if they occurred before hospital discharge. For the six trials (or trial strata) with routine aspirin therapy, data on mortality and nonfatal events were available for 98 to 100 percent of the randomized patients (numbers given at top of columns), except for data on pulmonary embolism, which were available for only about 85 percent. For the 21 trials (or trial strata) with no routine aspirin therapy, data on mortality were available for about 90 percent of all randomized patients; data on reinfarction, stroke, and pulmonary embolism for 75 to 85 percent; and data on major bleeding episodes for only about 60 percent. A few of the trials without routine aspirin therapy had 2:1 randomization, and the control group was counted twice in the present analyses to maintain balance.21 Plus–minus values are SD. †Of the patients in these trials, 14 percent were given fibrinolytic therapy. A total of about 100 additional patients were randomly assigned to treatment in several of these trials, but their treatment-group allocation and outcome are unknown. ‡Of the patients in these trials, 93 percent were given fibrinolytic therapy. N Engl J Med 1997; 336:847–860

低分子肝素 低分子肝素可用于TNK-tPA溶栓的后续抗凝治疗 除此之外不建议LMWH作为溶栓的后续抗凝治疗

LMWH在AMI患者中的应用 CHEST 2004; 126:549S–575S 对于接受TNK-tPA溶栓、年龄小于75岁、肾功能代偿期（男性Cr< 2.5 mg/dL；女性< 2.0mg/dL）的患者，建议给予依诺肝素（静脉30mg bolus；随后皮下注射1 mg/kg q12h）抗凝治疗至溶栓后7日 CHEST 2004; 126:549S–575S

直接凝血酶抑制剂 DTIs仅用于已知或可能患有肝素诱导的血小板减少性症患者溶栓的后续抗凝治疗

STEMI的抗栓治疗策略 接受溶栓治疗的患者 阿司匹林＋氯吡格雷＋短期普通肝素/低分子肝素 接受直接PCI的患者 阿司匹林＋氯吡格雷＋GP IIb/IIIa受体拮抗剂＋短期普通肝素/低分子肝素

抗栓治疗在ACS治疗中的地位 对于非ST段抬高的ACS，抗栓治疗可以阻止血栓进发展 对于ST段抬高的ACS，抗栓治疗可以提高溶栓再通率

ICTUS研究－－严峻的Challenge

ICTUS研究 最近发表的ICTUS研究结果表明在接受强化药物治疗（阿司匹林＋低分子肝素48小时＋氯吡格雷＋强化降脂；介入组另加用阿昔单抗）的ACS患者，早期介入和选择性介入策略的1年终点事件率分别为22.7％和21.2％ (RR1.07; 95%CI 0.87 to 1.33; P=0.33) N Engl J Med 2005;353:1095-104

Invasive or Conservative from ICTUS N Engl J Med 2005;353:1095-104

抗栓治疗在ACS治疗中的地位 两组患者均接受了积极抗凝、抗血小板及强化降脂治疗，可能正是这些被低估了的辅助药物治疗弥合了两组之间的差距 ICTUS研究的结果出人意料，虽然其中存在多种因素的影响，但是应该看到选择性介入组的1年死亡率很低（2.5%，与早期介入组相同） N Engl J Med 2005;353:1159-161

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