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Hidden Menace -Stent Thrombosis in Drug Eluting Stent Era

Hidden Menace -Stent Thrombosis in Drug Eluting Stent Era. Prof. Baogui SUN Shanghai First People’s Hospital. What Are We Worrying About?. Stent Thrombosis. Definite/Confirmed Acute coronary syndrome AND [Angiographic confirmation of thrombus or occlusion OR

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Hidden Menace -Stent Thrombosis in Drug Eluting Stent Era

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  1. HiddenMenace-Stent ThrombosisinDrugElutingStent Era Prof. Baogui SUN Shanghai First People’s Hospital

  2. What Are We Worrying About? Stent Thrombosis

  3. Definite/Confirmed Acute coronary syndromeAND [Angiographic confirmation of thrombus or occlusion OR Pathologic confirmation of acute thrombosis] Probable Unexplained death within 30 days Target vessel MI without angiographic confirmation of thrombosis or other identified culprit lesion Possible Unexplained death after 30 days ARC Definition of Stent Thrombosis

  4. TimingClassification ofStentThrombosis ST = stent thrombosis; SAT = subacute stent thrombosis; LST = late stent thrombosis; VLST = very late stent thrombosis. Adapted from Bhatt. J Invasive Cardiol. 2003;15(suppl B):3B.

  5. Late ST 61 pts (40%) Early ST 91 pts (60%) DES definite STincidence:Bern - Rotterdam Cohort Study Daemen, Wenaweser et al. Lancet 2007;369:667-78 N=8146 0.6% / year Incidence density: 1.3 / 100 patient years

  6. DESDefinite ST Incidence:Bern-Cohort Study @ 5 Years Wenaweser P et al. ESC 2008 0.52% (95% CI=0.42-0.62)/ year between 30 days and 5 years

  7. Overall Incidence of ST with DES CYPHER TAXUS XIENCE ENDEAVOR BIOMATRIX 3 1.9 1.6 2 2 1.4 1.8 % 1 1.1 0.8 0.8 0.7 1 0.8 0.5 0.5 0.6 0.4 0.3 0.2 0 0 ARTS II SIRTAX TAXUS II REALITY ISAR-DM TAXUS V SIRTAX ISAR-DM SIRIUS TAXUS IV TAXUS VI C-SIRIUS E-SIRIUS REALITY Spirit III Leaders Endeavor I Endeavor II

  8. Stent Design/Length Polymer Surface Drugs Intervention Residual Dissection Incomplete Stent Apposition Antithromobotic Medication Lesion Vessel Size Thrombus Causes of Stent Thrombosis Patient Genetic Polymorphism Reduced LV-EF Acute Coronary Syndrome Hematology Disorder Drugs Resistance Drug-drug Interaction Duration of Antiplatelet Treatement STENT THROMBOSIS Vessel Reaction Vessel Remodelling Hypersensitivity Reaction Delayed Healing

  9. Procedure and Lesion- related Parameters • Use of multiple stents • Small vessel diameter • Residual dissection • Geographic miss • Slow flow • Long and/or bifurcation lesions • Mal-apposition and/or under-expansion of the stent

  10. Patient Characteristics • Diabetes • Acute Coronary Syndromes (especially STEMI) • Left ventricular dysfunction • Renal failure • Advanced age • High platelet reactivity

  11. Anti-platelet therapy Reasons of ST in pts with anti-platelet therapy • Inadequate intensity of therapy (i.e. non-dual platelet inhibition or insufficient dose) • Non-compliance • Premature cessation of anti-platelet therapy

  12. Antiplatelet therapy at time of ST occurrenceBern-Rotterdam Cohort Study @ 5 YearsWenaweser P et al. ESC 2008

  13. Impact of Platelet Reactivity after Clopidogrel Administration on Drug-Eluting Stent ThrombosisBuonamici P et al JACC 2007 p<0.001 p<0.001 p=ns p<0.001

  14. Stent Characteristics • Stent design and structure • Strut profile or thickness • Polymer nature and type • Drug which stent coated

  15. Early Stent Thrombosis Triton TIMI 38 – Prasugrel vs. Clopidogrel in ACS Patients With Stents Wiviott SD et al. Lancet 2008;371:1353-63 Overall Stent Thrombosis Late Stent Thrombosis

  16. Predictor: Length of Stent OR=2.75 (1.55-4.88) OR=1.08 (1.06-1.1) OR=1.03 (1.00-1.05) OR=1.02 (1.00-1.04) OR=1.01 (1.00-1.03) Odds Ratio Iakovou et al JAMA 2005 Park et al Am J Card 2006 Machecourt et al JACC 2007 De la Torre et al JACC 2008 Airoldi et al Circulation 2007

  17. Predictor: Bifurcated Lesion OR=12.9 (4.7-35.8) OR=6.4 (2.9-14.1) Odds Ratio OR=4.4 (2.0-10.0) OR=2.4 (1.1-5.6) Roy et al J Interv Card 2007 Ong et al JACC 2005* Iakovou et al JAMA 2005 Kuchulakanti et al Circulation 2006 *in setting of AMI Joner et al JACC 2006

  18. Predictor: ACS OR=12.4 (1.7-89.7) OR=2.3 (1.3-4.0) OR=1.8 (1.1-2.7) HR=2.6 (1.3-4.9) Odds/Hazard Ratio De la Torre et al JACC 2008 Park et al Am J Card 2006 Daemen et al Lancet 2007 Urban et al Circulation 2006

  19. Impact of Thrombus Burden on Risk of ST With DES in Pts With STEMISianos G et al. J Am Coll Cardiol 2007;50:573-83 Independent Predictors of ST Variable Hazard Ratio 95% CI Age 0.6 0.4-0.8 Index ST 6.2 2.1-18.9 Bifurcation 4.1 1.6-10.0 Thrombectomy 0.1 0.01-0.8 Large thrombus 8.7 3.4-22.5

  20. Predictor: Diabetes OR=2.0 (0.8-4.9) OR=2.8 (1.7-4.3) OR=2.7 (1.4-5.2) HR=3.7 (1.7-7.9) HR=2.0 (1.1-3.8) HR=2.2 (1.1-4.3) HR=1.75 (1.0-3.0) Odds/Hazard Ratio Kuchulakanti Circ 2006 Urban Circ 2006 Machecourt JACC 2007 Iakovou JAMA 2005 Daemen Lancet 2007 Iijima Am J Card 2007 De la Torre JACC 2008

  21. DES vs BMSA cohort of 9,175 patients treated with either BMS or DES (SES or PES), all patients with angiographically documented ST were identified as cases Adjusted Resultswith interaction terms for time since PCI Early period: 0-30 days OR 0.59, 95% CI .35 - 1.01 Late period: 31-180 days OR 0.52, 95% CI .16 – 1.75 Very late period: > 180 days OR 9.4, 95% CI 2.56 – 34.70 0-30 days Time after PCI 31-180 days >180 days FavoursDES Favours BMS Favors DES Favors BMS .1 .2 .5 1 2 5 10 20 50 100 .1 .2 .5 1 2 5 10 20 50 100 Odds Ratio Odds Ratio Wenaweser et al. ACC 2007

  22. Probable Causes of Late Stent Thrombosis • Chronic inflammatory reaction to the polymer or drug • Hypersensitivity to the polymer or drug • Failure of stents to reendothelialize completely • Late incomplete stent apposition • Disease progression

  23. Late Incomplete Stent Apposition Baseline 8 mo follow-up SIRIUS Trial: 7/80 (8.7%) patients, no 12-month MACE Ako J. et al. JACC 2005;46:1002-5

  24. Post-DES: Pathophysiologic Mechanism Abnormal Vasomotion Delayed Healing Endothelialization Joner et al. JACC 2006 Togni et al. JACC 2005 Delayed Endothelialization Vessel Remodeling Kotani et al. JACC 2006 Cook et al. Circulation 2007

  25. Clinical Outcomes of ST • Sudden Cardiac Death: extremely dangerous • Non-fatal STEMI & NSTEMI: most probably • Malignant Arrhythmias: atypical • Chronic Total Occlusion: gradually and asymptomatic

  26. Treatment of Stent Thrombosis Ⅰ. Repeated PCI: most of pts Ⅱ. Drug therapy: all of pts Ⅲ. Emergent CABG: some of pts

  27. Oral Medication • Triple Antiplatelet Therapy: Clopidogrel & ASA & Cilostazol • Double Dosage of Clopidogrel: 150mg per day. • Prolonged Dual Antiplatelet Drug Therapy: >12 month ? longer is better? • Dual Antiplatelet Drug Therapy & Oral Anticoagulation: with warfarin ?

  28. Prevention of Stent Thrombosis • Identification of High Risk Pts modification of risks • Avoidance of Abused Stent Deployment long stent, bifurcation stenting, stent overlapping • Optimization of the Stent Deployment no residual dissention,improve stent expansion • Optimal anti-platelet therapy evaluate anti-platelet reactivity in high risk pts • Prior to BMS in pts with low restenosis to the full extent possible

  29. A Case of Very late ST

  30. AMI for the First Time(22/Jun/2003) • Female,55 years old • Chest Pain for 13 hrs,Medicine Treatment only in other Hospital, and to Our Hospital 1.5 Month later • No History of Hypertension、DM、Dyslipidemia and Smoking • ECG:V1~V2→QS,V3 → rS,V1~V3 → inversed T wave • UCG:Slight Decreased Movement of Anterior Wall

  31. CAG (7/Aug/2003):Total Occlusion of LAD

  32. The Result:Satisfied or Not ?

  33. After PCI • Clopidogrel was Stopped by the Pt 3-month after PCI • ASA 、Statin、ACEI、Beta-blocker were kept in using • Symptom Free for 2 years, and Angina occurred 3 times in last 6 months before administration

  34. AMI for the Second Time(11/Nov/2005)----27 Months Later • Chest Pain for 4 hrs • ECG: V2~V6→Elevated ST Segment for 0.1~0.6mV • Markers of Myocardium:Normal for TNI、CK-MB、MYO • Primary PCI: 11/Nov/2005

  35. CAG:Stent Thrombosis with TIMI II Flow, LCX Affected What to do?

  36. 10 days later Incomplete Stent Apposition Tirofiban and IABP

  37. AMI for the Third Time(11/Aug/2006)----36 Months Later • Chest Pain for 3 hrs • ECG: V2~V6→Elevated ST Segment for 0.1~0.5mV • Markers of Myocardium:Normal for TNI、CK-MB、MYO • Primary PCI: 11/Aug/2006

  38. CAG:LAD Occluded with In-stent Thrombosis, LCX AffectedWhat to do?

  39. PTCA:Wire: ATW/BMWBallon: Sprinter 2.5*15mm

  40. Thank You !

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