袁晋青pci后抗血小板治疗tcc课件

介入术后抗血小板治疗 中国医学科学院 阜外心血管病医院 袁晋青 一抗血小板药物作用机制和阿 司匹林抵抗 不同的抗血小板药物作用机制不同的抗血小板药物作用机制 胶原 凝血酶 TXA2 阿司匹林 ADPADP (纤维蛋白原受体） 氯吡格雷 TXA2 ADP 双嘧达莫 磷酸二酯酶 ADP Gp IIb/IIIa激活 COXCOX 盐酸噻氯匹定 ADP = adenosine diphosphate, TXA2 = thromboxane A2, COX = cyclooxygenase. Schafer AI. Am J Med. 1996;101:199209. Category % OR Acute MI Acute stroke Prior MI Prior stroke/TIA Other high risk Coronary artery disease (unstable angina, heart failure) Peripheral arterial disease (intermittent claudication) 22 2 % High risk of embolism (atrial fibrillation) Other (diabetes mellitus) All trials1.00.50.01.5 2.0 Control BetterAntiplatelet Better Antithrombotic Trialists Collaboration (ATC): Efficacy of Antiplatelet Therapy on Vascular Events* * Vascular events = MI, stroke, or vascular death. OR, odds reduction; MI, myocardial infarction; TIA, tranient ischemic attack. Antithrombotic Trialists Collaboration. BMJ. 2002;324:71-86. (with permission) Aspirin Resistance: More Than Just a Laboratory Curiosity? Bhatt DL. J Am CollCardiol.2004;43:1127-1129. Genetic Polymorphisms COX-1 GP IIIa receptor Collagen receptor vWF receptor Cellular Factors Insufficient suppression of COX-1 Overexpression of COX-2 mRNA Erythrocyte-induced platelet activation Increased norepinephrine Generation of 8-iso-PGF2 Clinical Factors Failure to prescribe Noncompliance Nonabsorption Interaction with ibuprofen Interaction with naproxen Aspirin Resistance Aspirin Resistance and the Risk of Cardiovacular Events in High Risk Patients 5529 pts from HOPE study with baseline urine samples Case (n=488) Pts with CV events after randomization Controls (n=488) Pts without CV events after randomization Urinary 11-dehydro Thromboxane B2 (ng/mmol creatinine) 33.8 1.0 1.3 1.4 1.8 MI, stroke or CV death (P=.01) Odd Ratio Hypothesis: Incomplete inhibition of thromboxane B2 increases risk of cardiovascular event Adapted from Eikelboom JW, et al. Circulation. 2002;105:1650-1655. VerifyNowASA, ASA/clopidogrel (n=464), 26.9% ASA resistant Aspirin-resistant Aspirin-sensitive n=125 P=0.007 n=339 CV Death MI CVA/TIA HospUA Cumulative incidence of composite end point(%) Follow-up time (days) ASA Response and Long-Term CV Events 二、氯吡格雷的早期和长期应用 什么时间用？用多长时间？ CLARITY 急救亚组研究: 住院前氯吡格雷 对比安慰剂(加溶栓治疗) ECG显示ST段恢复的患者 (%) 在救护车上给予氯吡格雷的患者伴ST段恢复 Verheugt F et al. J Thromb Thrombolysis 2006;Dec 6 epub p=0.02 p=0.05 给予负荷剂量后的时间 3,491名 12个月(n=252) : DES + 氯吡格雷0.03 g/L) 20 15 10 5 0 051015202530 Days After Randomization Placebo Group (N=1010) Abciximab Group (N=1012) Troponin 0.03 g/L Log-Rank p = 0.02 Troponin 0.03 g/L Log-Rank p = 0.98 JAMA 2006; 295:1531-38 % 02 4 681012 Follow-up duration (months) % No. at risk Log-Rank, P=0.0192 0 1 2 3 4 5 0.8% 0.1% Triple group 965 957 953 Dual group 965 948 942 The DECREASE Registry Cumulative incidence of stent thrombosis Dual antiplatelet therapy (n=965) Triple antiplatelet therapy (n=965) 02 4 681012 Follow-up duration (months) % No. at risk Log-Rank, P=0.0744 0 1 2 3 4 5 2.6% 1.4% Triple group 965 955 950 Dual group 965 948 940 Cumulative incidence of Death or MI Dual antiplatelet therapy (n=965) Triple antiplatelet therapy (n=965) 研究设计 氯吡格雷高剂量组 氯吡格雷 600 mg负荷剂量第1天， 接第2-7天150 mg; 第8-30天75 mg 氯吡格雷标准剂量组 氯吡格雷 300 mg (+安慰剂) 第1天， 接第2-7天75 mg (+安慰剂); 第8-30天75 mg 随机分组随机分组 ASA 低剂量组 第1天至少 300 mg; D2 - D30 75100 mg ASA 高剂量组 第1天至少 300 mg; D2- D30 300 mg325 mg ASA高剂量组 第1天至少 300 mg; D2- D30 300 mg325 mg ASA低剂量组 第1天至少 300 mg; D2 - D30 75100 mg 计划早期介入治疗的 UA/NSTEMI患者， 即有意在24小时内尽早行PCI的患者 随机分组 PCI: 经皮冠脉介入术 UA/NSTEMI: 不稳定心绞痛/非ST段抬高型心梗 CURRENT 四、新型抗血小板药物的研究 JUMBO-TIMI 26 three doses of prasugrel vs clopidogrel in elective or urgent PCI (safety evaluation) Circulation 2005; 11:3366-73 1.7 1.2 % 7.2 9.4 % Significant non-CABG Bleeding at 30days P=0.77 MACE at 30 days HR 0.76 P=0.26 PRINCIPLE TIMI 44PRINCIPLE TIMI 44 (Planned Elective PCI) PRIMARY EP Acute Phase: IPA 20 uM ADP Prasugrel 60 mg P0.0001 for each IPA (%; 20 mM ADP) Hours Circulation 2007;116:2923-32 Prasugrel 10 mgPrasugrel 10 mg Difference Between Treatments: 14.9 95% CI 10.6 19.3, P0.0001 IPA (%; 20 mM ADP) Days Circulation 2007;116:2923-32 PRINCIPLE TIMI 44PRINCIPLE TIMI 44 PRIMARY EP Chronic Phase: IPA 20 uM ADP Days Primary Endpoint(%) 10 0 0 30 15 5 Prasugrel Clopidogrel 60 90180 270 360 450 HR 0.77HR 0.77 P=0.0001P=0.0001 HR 0.80HR 0.80 P=0.0003P=0.0003 12.112.1 (781)(781) 9.99.9 (643)(643) HR 0.81HR 0.81 (0.73-0.90)(0.73-0.90) P=0.0004P=0.0004 NNT=46NNT=46 ITT=13,608 LTFU=14(0.1%) TRITON TIMI-38TRITON TIMI-38 ACS (STEMI or UA NSTEMI) 357: 2001-15 ARD 0.6 HR 1.32 P =0.03 NNH =167 ARD 0.5 HR 1.52 P =0.01 ARD 0.2 P =0.23 ARD 0.3 P =0.002 ARD 0% P =0.74 TRITON TIMI-38 Bleeding Events Safety Cohort (n=13,457) ICH in Pts w Prior Stroke/ TIA (N=518) Clop 0(0) % Pras 6(2.3)% (P=0.02) N Engl J Med 2007; 357: 2001-15 Days Endpoint(%) 10 0 0 30 15 5 Prasugrel Clopidogrel 60 90180 270 360 450 12.112.1 9.99.9 TRITON TIMI 38 Balance of Efficacy and Safety CV Death / MI / Stroke 2.42.4 1.81.8 TIMI Major NonCABG Bleeds 138 events HR 0.81 (0.73-0.90) P =0.0004 NNT =46 35 events HR 1.32 (1.03-1.68) P =0.03 NNH =167 N Engl J Med 2007; 357: 2001-15 Optimization of Prasugrel maintenance dosing in a minority of patients may help improve the benefit: risk balance Safety Significant increase in serious bleeding (32% increase) Avoid in pts with prior CVA/ TIA Efficaency 1. A significant reduction in: CV Death/ MI/ Stroke 19% Stent Thrombosis 52% uTVR 34% MI 24% 2. An early and sustained benefit 3. Across ACS spectrum Net clinical benefit significant favored Prasugrel TRITON TIMI-38TRITON TIMI-38 Higher IPA to Support PCI Prasugrel 60 mg LD/ 10mg MD vs Clopidogrel 300 mg LD/ 75 mg LD N Engl J Med 2007; 357: 2001-15 2007年ESC NSTE-ACS指南对氯吡格雷的推荐 I IIa IIb III 所有患者立即给予300mg负荷剂量氯吡格雷，再以每天75mg维持 剂量治疗。 除非有极高出血风险，否则应维持使用12个月 阿司匹林禁忌，改用氯吡格雷 考虑进行介入或PCI治疗的患者，可采用600mg负荷剂量以更快 达到抑制血小板功能 B A A 2007年AHA/ACC NSTE-ACS 指南对氯吡格雷的推荐 B A A 如对阿司匹林过敏或胃肠道不耐受，应服用氯吡格雷（负荷剂量 300600mg，维持剂量75mg/天） 采用介入治疗的患者在冠脉造影诊断之前应在阿司匹林的基础上 联合使用氯吡格雷（负荷剂量300600mg，维持剂量75mg/天） 或静脉GP IIb/IIIa受体抑制剂。 采用保守治疗患者，应在其入院后尽早联合使用氯吡格雷（负荷 剂量300600mg，维持剂量75mg/天）阿司匹林和抗凝治疗，至 少持续1个月，最好持续1年 A I IIa IIb III 20072007年国际权威指南推荐对所有年国际权威指南推荐对所有ACSACS患者都应患者都应 从急性期到长期持续使用氯吡格雷从急性期到长期持续使用氯吡格雷 20092009年中国年中国PCIPCI治疗指南治疗指南 阿司匹林推荐阿司匹林推荐 I I IIa IIa IIb IIb IIIIII 术前已经接受长期ASA治疗：PCI前服用 100300mg 以往未服用ASA：PCI术前至少2h，最好24h前 给予300mg PCI术后，对于无ASA过敏或高出血风险的患者，口 服100300mg/d，BMS至少服用1个月，雷帕霉素洗 脱支架服用3个月，紫杉醇洗脱支架服用6个月，之后 改为100mg/d长期服用 对于担心出血风险者，可在支架术后的初始阶段给予 75100mg/d低剂量ASA治疗 B A C C 20092009年中国年中国PCIPCI治疗指南治疗指南 氯吡格雷氯吡格雷PCIPCI术前推荐术前推荐 I I IIa IIa IIb IIb IIIIII