支架內血栓李建平

1、支架內血栓In-Stent Thrombosis,北京大學第一醫(yī)院 李建平,,Definite/Confirmed （肯定的）Acute coronary syndrome AND[Angiographic confirmation of thrombus or occlusion ORPathologic confirmation of acute thrombosis]Probable （可能的）Unexplaine

2、d death within 30 daysTarget vessel MI without angiographic confirmation of thrombosis or other identified culprit lesionPossible （不能排除的）Unexplained death after 30 days,ARC 支架內血栓定義,支架內血栓的預后,Similar mortality observed

3、for SES and BMS thrombosis,Pooled Data from RAVEL, SIRIUS, C-SIRIUS, E-SIRIUS,支架內血栓發(fā)生時間,ST = stent thrombosis; SAT = subacute stent thrombosis;LST = late stent thrombosis; VLST = very late stent thrombosis.Adapted from

4、 Bhatt. J Invasive Cardiol. 2019;15(suppl B):3B.,Stent Thrombosis (%),支架內血栓與抗凝、抗血小板治療,ASA und Ticlopidine,ASA und Anticoagulation,ASA und Clopidogrel,,,,ASA = Acetylsalicylic acidDES: Drug-eluting stent,,Bare Metal Sten

5、t,Prasugrel?,DES肯定的ST發(fā)生率:Bern - Rotterdam Cohort Study Daemen, Wenaweser et al. Lancet 2019;369:667-78,N=8146,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,0,,1,,2,,3,,4,Time since PCI in years,0,1,2,3,4,5,Cumulative incidenc

6、e, %,Incidence density1.0 / 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發(fā)生率:Bern-Rotterdam Cohort Study 4 YearsWenaweser P et al. J Am Coll Cardiol 2019, 52, 1134-,,,,,,,,,,

7、,,,,,,,,,,,0.52% (95% CI=0.42-0.62)/ year between 30 days and 5 years,DES肯定的支架內血栓發(fā)生率:Bern-Cohort Study 5 YearsWenaweser P et al. ESC 2019,DES vs BMSA cohort of 9,175 patients treated with either BMS or DES (SES or PE

8、S), all patients with angiographically documented ST were identified as cases,Early Stent Thrombosis,RR=0.7695% CI =0.30-1.80P=0.55,RR=0.8095% CI =0.32-2.03P=0.79,Meta-analysisSES vs BMSBavry A et al. Am J Card 201

9、9,Meta-analysisPES vs BMSStone G et al. NEJM 2019,%,%,Very Late ST > 1 Year (Per Protocol),P=0.75,P=0.02,%,P=0.30,P=0.03,%,Stone G et al. NEJM 2019;356:998-1008,Kastrati A et al. NEJM 2019;356:1030-9,Sirolimus-Eluti

10、ng Stent,Paclitaxel-Eluting Stent,,SIRTAX – Definite ST 4 YearsWindecker S et al ESC 2019,2.0%,1.8%,2.8%,2.4%,3.7%,3.4%,Cumulative Incidence of Definite STin LEADERS (BES vs. SES)Windecker et al. Lancet, 2019, 372, 1

11、163-,Overall Incidence of ST with DES,,ENDEAVOR,,XIENCE,,BIOMATRIX,,High Risk of ST in All-Comer Patient Population and STEMI Patients,%,,,支架內血栓的病因,STENT THROMBOSIS,PatientGenetic PolymorphismReduced LV-EFAcute Coron

12、ary SyndromeHematology Disorder,,,DrugsResistanceDrug-drug InteractionDuration of AntiplateletTreatement,,,Vessel ReactionVessel RemodelingHypersensitivity ReactionDelayed Healing,早期支架內血栓的預測因素:殘留夾層/撕裂,,Bare Meta

13、l StentsMACE 30 daysSchühlen H et al. Circulation 2019,N=2,894,Drug-Eluting StentsMACE 30 daysBiondi-Zoccai G et al. EHJ 2019,N=2,418,%,P=0.01,P=0.01,Residual Dissection: Independent Predictor of MACE (OR=2.9)

14、,早期支架內血栓IVUS預測因素 With the Use of Sirolimus-Eluting StentsFujii K et al. J Am Coll Cardiol 2019;45:995-8,Minimal Stent CSA,P<0.001,mm2,Stent Expansion,Residual Stenosis,%,P<0.001,Stent Underexpansion and Residual

15、 Reference Segment Stenosis:Independent Predictors of Early Stent Thrombosis!,P<0.001,支架內血栓預測因素藥物反應異常 Wenaweser P et al. JACC 2019; 45(11):1748-52,,服藥后血小板活性與DES ST的關系Buonamici P et al JACC 2019,p<0.001,p<0.0

16、01,p<0.001,p=ns,,,Iakovou et alJAMA 2019,Park et alAm J Card 2019,Airoldi et alCirculation 2019,Kuchulakanti et alCirculation 2019,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/Ha

17、zard Ratio,過早停用抗血小板藥物是支架內血栓的重要預測因素,支架內血栓發(fā)生時的抗血小板治療 Bern-Rotterdam Cohort Study 5 YearsWenaweser P et al. ESC 2019,Triton TIMI 38 – Prasugrel vs. Clopidogrel in ACS Patients With StentsWiviott SD et al. Lancet 2019;3

18、71:1353-63,Overall Stent Thrombosis,Early Stent Thrombosis,Late Stent Thrombosis,Park et alAm J Card 2019,Airoldi et alCirculation 2019,Iakovou et alJAMA 2019,Machecourt et alJACC 2019,OR=1.03(1.00-1.05),OR=1.01(1.

19、00-1.03),OR=2.75(1.55-4.88),Odds Ratio,支架內血栓的預測因素-支架長度,OR=1.02(1.00-1.04),OR=1.08(1.06-1.1),De la Torre et alJACC 2019,Roy et alJ Interv Card 2019,Kuchulakanti et alCirculation 2019,OR=4.4(2.0-10.0),Odds Ratio,支架內

20、血栓的預測因素-分叉病變,OR=2.4(1.1-5.6),Iakovou et alJAMA 2019,OR=6.4(2.9-14.1),Ong et alJACC 2019*,OR=12.9(4.7-35.8),*in setting of AMI,Joner et al JACC 2019,Park et alAm J Card 2019,Daemen et alLancet 2019,Urban et alCirc

21、ulation 2019,OR=12.4(1.7-89.7),OR=2.3(1.3-4.0),OR=1.8(1.1-2.7),Odds/Hazard Ratio,支架內血栓的預測因素-ACS,De la Torre et alJACC 2019,HR=2.6(1.3-4.9),Impact of Thrombus Burden on Risk of ST With DES in Patients With STEMISia

22、nos G et al. J Am Coll Cardiol 2019;50:573-83,Independent Predictors of ST,Kuchulakanti Circ 2019,Urban Circ 2019,IakovouJAMA 2019,DaemenLancet 2019,Machecourt JACC 2019,OR=2.0(0.8-4.9),OR=2.8(1.7-4.3),HR=3.7(1.7

23、-7.9),HR=2.0(1.1-3.8),OR=2.7(1.4-5.2),Odds/Hazard Ratio,支架內血栓的預測因素-糖尿病,IijimaAm J Card 2019,HR=2.2(1.1-4.3),HR=1.75(1.0-3.0),De la TorreJACC 2019,晚期支架內血栓的可能原因,Chronic inflammatory reaction to the polymer or drugHy

24、persensitivity to the polymer or drugFailure of stents to completely reendothelialize completelyLate incomplete stent appositionDisease progression,多聚物高敏,獲得性晚期支架貼壁不良,Baseline

25、 8 mo follow-up,SIRIUS Trial: 7/80 (8.7%) patients, no 12-month MACE Ako J. et al. JACC 2019;46:1002-5,Cook et al. Circulation 2019,Kotani et al. JACC 2019,Joner et al. JACC 2019,Togni et al.

26、JACC 2019,Abnormal Vasomotion,Delayed Healing,Delayed Endothelialization,Vessel Remodeling,DES后病生理機制,Endothelialization,小結,DES支架內血栓發(fā)生率：Early: 0.5% - 1.6%Late/Very late: 0.3% - 0.6%預測因素Residual dissection, stent unde

27、rexpansionDiabetes, ACS, bifurcation stenting, stent length, thrombus burden, late aquired stent malapposition, ineffective platelet inhibition,支架內血栓的預防,高危病人的辨認避免過度支架長支架, 分叉支架, 支架重疊支架植入的理想結果 無殘留撕裂/夾層支架膨脹良好增加抗血小板治療

28、的有效性高危病人評估抗血小板藥物的反應性再狹窄低危病人中使用BMS,,,專家共識,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

29、 lesion predictors)Data from multiple sources indicate thatDES are associated with delayed healingresponses and increased inflammationThe causes of late DES thrombosis are multi-factorial; device, procedural, and pa

30、tientfactors (often multiple = perfect storm),,,專家共識,FDA DES Panel Meeting,There may be a link between post-DES reduced neo-intimal hyperplasia (late loss) and delayed late healing responses which contributes to late st

31、ent thrombosis DES stent thrombosis is highly definition dependent; need for revised standardizeddefinitions and adjudication methods (ARC) to facilitate inter-study comparisons,,,專家共識,“Off-label DES use – increased

32、incidence of late DES thrombosis and death/MI cw “on-label”, butinadequate controls; results inconsistent! Few RCTs (underpowered); FDA sanctioned registries = insufficient sample size and FU, represents major data gap

33、 and source of concernLarge population studies (SCAAR) fraught with methodologic flaws (e.g. risk adjustment issues),,,專家共識,Duration of dual anti-platelet therapy should extend beyond the present product labelsOne year

34、 is reasonable compromise (esp. for“off-label” DES use)Must balance against the increased risk ofbleeding with dual anti-platelet therapyAdditional studies immediately required tobetter clarify optimal anti-platelet

35、 therapy,,,專家共識,Assess patient and lesion characteristics to establish restenosis risk profileDetermine relative value of DES vs. BMS inevery patient (no more “unrestricted” use) Consider both on-label and off-label

36、situations (ironically, off-label use scenarios may be more compelling)Increased restenosis risk = favor DESIncreased safety concerns = favor No DES,,,專家共識,Assess patient factors which may preclude long-term (at least

37、 one year) dual AP therapyPlanned or possible intercurrent surgeryBleeding Hx or tendenciesOther concomitant medications (e.g. coumadin)Socio-economic factors which may affect Plavix compliance,,,專家共識,Consider altern

38、atives to DES, if risk-benefit assessments prove unfavorableCABG – unprotected LM disease, complex MVD (esp. diabetics), recurrent ISR (esp. VBT) BMS – Plavix dependence concerns, large (>4mm diameter) vessels, ? A

39、MI pts, ? low restenosis risk lesionsBalloon PCI – sidebranch in bifurcations (provisional stent only), small vessels in distal locations,,,專家共識,Optimize DES implantation techniquesAdequate lesion preparation (pre-dil

40、atation)High pressure implantation methodologies (like previous BMS strategies)Avoid undersizing and inflow/outflow obstruction (mod stenoses or dissections)Implant stent edges into normal references segmentsConsider

41、 IVUS guidance (esp. LAD),,,專家共識,Careful explanations and open communication with patients and familiesCareful pre-treatment historyDiscussion with EVERY pt re: risks and benefits of DES vs. alternative therapiesOngoi