1、支架内血栓 In-Stent Thrombosis,北京大学第一医院 李建平,Definite/Confirmed （肯定的） Acute coronary syndrome AND Angiographic confirmation of thrombus or occlusion OR Pathologic confirmation of acute thrombosis Probable （可能的） Unexplained death within 30 days Target vessel MI without angiographic confirmation of thrombos
2、is or other identified culprit lesion Possible （不能排除的） Unexplained death after 30 days,ARC 支架内血栓定义,支架内血栓的预后,Similar mortality observed for SES and BMS thrombosis,Pooled Data from RAVEL, SIRIUS, C-SIRIUS, E-SIRIUS,支架内血栓发生时间,ST = stent thrombosis; SAT = subacute stent thrombosis; LST = late stent thro
3、mbosis; VLST = very late stent thrombosis. Adapted from Bhatt. J Invasive Cardiol. 2003;15(suppl B):3B.,Stent Thrombosis (%),支架内血栓与抗凝、抗血小板治疗,ASA und Ticlopidine,ASA und Anticoagulation,ASA und Clopidogrel,ASA = Acetylsalicylic acid DES: Drug-eluting stent,Bare Metal Stent,Prasugrel?,DES肯定的ST发生率: Ber
4、n - Rotterdam Cohort Study Daemen, Wenaweser et al. Lancet 2007;369:667-78,N=8146,0,1,2,3,4,Time since PCI in years,0,1,2,3,4,5,Cumulative incidence, %,Incidence density 1.0 / 100 pt years,3.3%,3.5,0.53% (95% CI=0.44-0.64)/ year,192 definite ST cases,DES肯定的ST发生率: Bern-Rotterdam Cohort Study 4 Years
5、Wenaweser P et al. J Am Coll Cardiol 2008, 52, 1134-,0.52% (95% CI=0.42-0.62)/ year between 30 days and 5 years,DES肯定的支架内血栓发生率: Bern-Cohort Study 5 Years Wenaweser P et al. ESC 2008,DES vs BMS A cohort of 9,175 patients treated with either BMS or DES (SES or PES), all patients with angiographically
6、documented ST were identified as cases,Early Stent Thrombosis,RR=0.76 95% CI =0.30-1.80 P=0.55,RR=0.80 95% CI =0.32-2.03 P=0.79,Meta-analysis SES vs BMS Bavry A et al. Am J Card 2005,Meta-analysis PES vs BMS Stone G et al. NEJM 2007,%,%,Very Late ST 1 Year (Per Protocol),P=0.75,P=0.02,%,P=0.30,P=0.0
7、3,%,Stone G et al. NEJM 2007;356:998-1008,Kastrati A et al. NEJM 2007;356:1030-9,Sirolimus-Eluting Stent,Paclitaxel-Eluting Stent,SIRTAX Definite ST 4 Years Windecker S et al ESC 2008,2.0%,1.8%,2.8%,2.4%,3.7%,3.4%,Cumulative Incidence of Definite ST in LEADERS (BES vs. SES) Windecker et al. Lancet,
8、2008, 372, 1163-,Overall Incidence of ST with DES,ENDEAVOR,XIENCE,BIOMATRIX,High Risk of ST in All-Comer Patient Population and STEMI Patients,%,支架内血栓的病因,STENT THROMBOSIS,Patient Genetic Polymorphism Reduced LV-EF Acute Coronary Syndrome Hematology Disorder,Drugs Resistance Drug-drug Interaction Dur
9、ation of Antiplatelet Treatement,Vessel Reaction Vessel Remodeling Hypersensitivity Reaction Delayed Healing,早期支架内血栓的预测因素: 残留夹层/撕裂,Bare Metal Stents MACE 30 days Schhlen H et al. Circulation 1998,N=2,894,Drug-Eluting Stents MACE 30 days Biondi-Zoccai G et al. EHJ 2006,N=2,418,%,P=0.01,P=0.01,Residua
10、l Dissection: Independent Predictor of MACE (OR=2.9),早期支架内血栓IVUS预测因素 With the Use of Sirolimus-Eluting Stents Fujii K et al. J Am Coll Cardiol 2005;45:995-8,Minimal Stent CSA,P0.001,mm2,Stent Expansion,Residual Stenosis,%,P0.001,Stent Underexpansion and Residual Reference Segment Stenosis: Independe
11、nt Predictors of Early Stent Thrombosis!,P0.001,支架内血栓预测因素 药物反应异常 Wenaweser P et al. JACC 2005; 45(11):1748-52,服药后血小板活性与DES ST的关系 Buonamici P et al JACC 2007,p0.001,p0.001,p0.001,p=ns,Iakovou et al JAMA 2005,Park et al Am J Card 2006,Airoldi et al Circulation 2007,Kuchulakanti et al Circulation 2006,
12、OR=89.8 (29.9-270),HR=19.2 (5.6-65.5),HR=13.7 (4.0-46.7),OR=4.8 (2.0-11.1),Odds/Hazard Ratio,过早停用抗血小板药物是支架内血栓的重要预测因素,支架内血栓发生时的抗血小板治疗 Bern-Rotterdam Cohort Study 5 Years Wenaweser P et al. ESC 2008,Triton TIMI 38 Prasugrel vs. Clopidogrel in ACS Patients With Stents Wiviott SD et al. Lancet 2008;371:
13、1353-63,Overall Stent Thrombosis,Early Stent Thrombosis,Late Stent Thrombosis,Park et al Am J Card 2006,Airoldi et al Circulation 2007,Iakovou et al JAMA 2005,Machecourt et al JACC 2007,OR=1.03 (1.00-1.05),OR=1.01 (1.00-1.03),OR=2.75 (1.55-4.88),Odds Ratio,支架内血栓的预测因素-支架长度,OR=1.02 (1.00-1.04),OR=1.08
14、 (1.06-1.1),De la Torre et al JACC 2008,Roy et al J Interv Card 2007,Kuchulakanti et al Circulation 2006,OR=4.4 (2.0-10.0),Odds Ratio,支架内血栓的预测因素-分叉病变,OR=2.4 (1.1-5.6),Iakovou et al JAMA 2005,OR=6.4 (2.9-14.1),Ong et al JACC 2005*,OR=12.9 (4.7-35.8),*in setting of AMI,Joner et al JACC 2006,Park et al
15、 Am J Card 2006,Daemen et al Lancet 2007,Urban et al Circulation 2006,OR=12.4 (1.7-89.7),OR=2.3 (1.3-4.0),OR=1.8 (1.1-2.7),Odds/Hazard Ratio,支架内血栓的预测因素-ACS,De la Torre et al JACC 2008,HR=2.6 (1.3-4.9),Impact of Thrombus Burden on Risk of ST With DES in Patients With STEMI Sianos G et al. J Am Coll C
16、ardiol 2007;50:573-83,Independent Predictors of ST,Kuchulakanti Circ 2006,Urban Circ 2006,Iakovou JAMA 2005,Daemen Lancet 2007,Machecourt JACC 2007,OR=2.0 (0.8-4.9),OR=2.8 (1.7-4.3),HR=3.7 (1.7-7.9),HR=2.0 (1.1-3.8),OR=2.7 (1.4-5.2),Odds/Hazard Ratio,支架内血栓的预测因素-糖尿病,Iijima Am J Card 2007,HR=2.2 (1.1-
17、4.3),HR=1.75 (1.0-3.0),De la Torre JACC 2008,晚期支架内血栓的可能原因,Chronic inflammatory reaction to the polymer or drug Hypersensitivity to the polymer or drug Failure of stents to completely reendothelialize completely Late incomplete stent apposition Disease progression,多聚物高敏,获得性晚期支架贴壁不良,Baseline 8 mo foll
18、ow-up,SIRIUS Trial: 7/80 (8.7%) patients, no 12-month MACEAko J. et al. JACC 2005;46:1002-5,Cook et al. Circulation 2007,Kotani et al. JACC 2006,Joner et al. JACC 2006,Togni et al. JACC 2005,Abnormal Vasomotion,Delayed Healing,Delayed Endothelialization,Vessel Remodeling,DES后病生理机制,Endothelialization
19、,小结,DES支架内血栓发生率： Early: 0.5% - 1.6% Late/Very late: 0.3% - 0.6%预测因素 Residual dissection, stent underexpansion Diabetes, ACS, bifurcation stenting, stent length, thrombus burden, late aquired stent malapposition, ineffective platelet inhibition,支架内血栓的预防,高危病人的辨认 避免过度支架 长支架, 分叉支架, 支架重叠 支架植入的理想结果 无残留撕裂/
20、夹层 支架膨胀良好 增加抗血小板治疗的有效性 高危病人评估抗血小板药物的反应性 再狭窄低危病人中使用BMS,专家共识,FDA DES Panel Meeting,There is an increase in “very late” (1 yr) stent thrombosis associated with current DES 2-4 per 1000 pts per year (? continous hazard, ? patient and lesion predictors) Data from multiple sources indicate that DES are as
21、sociated with delayed healing responses and increased inflammation The causes of late DES thrombosis are multi- factorial; device, procedural, and patient factors (often multiple = perfect storm),专家共识,FDA DES Panel Meeting,There may be a link between post-DES reduced neo-intimal hyperplasia (late lo
22、ss) and delayed late healing responses which contributes to late stent thrombosis DES stent thrombosis is highly definition dependent; need for revised standardized definitions and adjudication methods (ARC) to facilitate inter-study comparisons,专家共识,“Off-label DES use increased incidence of late DE
23、S thrombosis and death/MI cw “on-label”, but inadequate controls; results inconsistent! Few RCTs (underpowered); FDA sanctioned registries = insufficient sample size and FU, represents major data gap and source of concern Large population studies (SCAAR) fraught with methodologic flaws (e.g. risk ad
24、justment issues),专家共识,Duration of dual anti-platelet therapy should extend beyond the present product labels One year is reasonable compromise (esp. for “off-label” DES use) Must balance against the increased risk of bleeding with dual anti-platelet therapy Additional studies immediately required to
25、 better clarify optimal anti-platelet therapy,专家共识,Assess patient and lesion characteristics to establish restenosis risk profile Determine relative value of DES vs. BMS in every patient (no more “unrestricted” use) Consider both on-label and off-label situations (ironically, off-label use scenarios
26、 may be more compelling) Increased restenosis risk = favor DES Increased safety concerns = favor No DES,专家共识,Assess patient factors which may preclude long-term (at least one year) dual AP therapy Planned or possible intercurrent surgery Bleeding Hx or tendencies Other concomitant medications (e.g.
27、coumadin) Socio-economic factors which may affect Plavix compliance,专家共识,Consider alternatives to DES, if risk-benefit assessments prove unfavorable CABG unprotected LM disease, complex MVD (esp. diabetics), recurrent ISR (esp. VBT) BMS Plavix dependence concerns, large (4mm diameter) vessels, ? AMI
28、 pts, ? low restenosis risk lesions Balloon PCI sidebranch in bifurcations (provisional stent only), small vessels in distal locations,专家共识,Optimize DES implantation techniques Adequate lesion preparation (pre-dilatation) High pressure implantation methodologies (like previous BMS strategies) Avoid
29、undersizing and inflow/outflow obstruction (mod stenoses or dissections) Implant stent edges into normal references segments Consider IVUS guidance (esp. LAD),专家共识,Careful explanations and open communication with patients and families Careful pre-treatment history Discussion with EVERY pt re: risks and benefits of DES vs. alternative therapies Ongoing (post-Rx) communication and careful FU re: dual AP compliance (instructions = NO Plavix discontinuation without MD approval)!,DES 风险 & 获益,治疗1000个病人可以预防100个再狭窄 同时可以预防10个再狭窄相关的心肌梗死 可能会因为晚期支架内血栓增加5个心肌梗死 获益风险,
