How to Predict & Prevent It! George D. Dangas, MD, FACC, FESC

Transcription

1 Stent Thrombosis How to Predict & Prevent It! George D. Dangas, MD, FACC, FESC Professor of Cardiology & Vascular Surgery Icahn School of Medicine at Mount Sinai New York, NY Καθηγητής Καρδιολογίας ΕΚΠΑ

2 History of Stent Thrombosis Stent thrombosis (%) % 1 STRESS 2 2 Colombo 3 3 ISAR PS Coumadin 3.5% 1993 High-pressure balloons and DAPT 1.4% % % STARS Schatz RA et al. Circulation.1991;83:148; 2. Fischman DL et al. N Engl J Med. 1994;331496; 3 Colombo A et al. Circulation.1995;91:1676; 4. Schömig A et al.circulation.1994,90:2716; 5. Leon M et al. N Engl J Med. 1998;339:1665; Joner M et al. J Am Coll Cardiol. 2006;48:193

3 Timing of ST After Stent Implantation Very Late > 1 year Late >30 days (but within 1 year) Early Subacute Acute ST 24 hours to 30 days 24 Hours Cutlip DE et al. Circulation. 2007;115:

4 Predictors of Stent Thrombosis The good (Patient), the bad (Procedure) and the ugly (Device) ACS / STEMI Diabetes Mellitus Chronic Kidney Disease LV Dysfunction Saphenous Vein Graft Patient Platelet Reactivity Premature cessation of DAPT APT Non-Responsiveness Malignancy Device Type of stent Polymer integrity and reactions Drug effects Covered Stents Incomplete Vascular Healing and / or Inadequate Neointimal Coverage Hypersensitivity to drug coating or polymer Neoatherosclerosis Stent Thrombosis Procedure Residual Edge Dissection Dissection Lesion / Stent Length Vessel / Stent Diameter Complex Lesions Incomplete Stent Apposition

5 Stent Thrombosis With Drug-Eluting Stents and Bioresorbable Scaffolds Evidence From a Network Meta-Analysis of 147 Trials A total of 147 trials including 126,526 patients Kang S et al., J Am Coll Cardiol Intv. 2016;9(12):

6 Impact of strut thickness Relative ex vivo thrombogenicity LDH Adsorbance for Stent Formulation / LDH Absorbance for ML Vision (81µm) 1,8 1,0 1,5 0 ML VISION (81 µm) TS Vision (162 µm) Xience V (96,6 µm) 0,8 Hematotoxilin and eosin staining, 3 days after implantation Computational models depicting flow alterations Kolandaivelu K et al., Circulation 2011; 123:

7 Pathobiology of ST with DES

8 INCOMPLETE STENT APPOSITION Positive Vessel Remodeling Thrombus Dissolution Stent Vessel Size Mismatch Attizzani GF et al., J Am Coll Cardiol Apr 15;63(14): Cook S et al., Circulation. 2007;115:

9 Stent Underexpansion Poses a ST Risk

10 Adjusted risk of definite or probable stent thrombosis across complex PCI components Giustino G et al; J Am Coll Cardiol Aug 25. pii: S (16)34935-X

11 CYP2C19 and Clopidogrel Responsiveness 429 Healthy Amish after Clopidogrel 75 mg X 7d P=1.5 X CPY2C19*2 explained 12% of variance in Clopidogrel Response Shuldiner AR et al., JAMA 2009;302(8):

12 Combined clinical and genetic model for ST risk prediction Combined Model AUC: 0.78; 95% CI: ; P < Genetic Model AUC: 0.68; 95% CI, ; P < Clinical Model AUC: 0.73; 95% CI, ; P < Cayla G. et al., JAMA. 2011;306:

13 N=3041 Meta-Analysis of OTR and Ischemic Events Post-PCI Increasing Risk With Greater Residual Reactivity * Log-rank P values adjusted for multiple comparisons Q1 taken as referent Brar S et al, J Am Coll Cardiol Nov 1;58(19):

14 ADAPT-DES: Unadjusted and Adjusted ST Rates According to PRU Stone G et al - Lancet 2013; 382:

15 ADAPT-DES IVUS SUBSTUDY: IVUS Planar Analysis A. Maehara TCT 2014

16 Use of IVUS Reduces Stent Thrombosis and Myocardial Infarction Results from the Prospective, Multicenter ADAPT-DES Study A. Maehara TCT 2014

17 STENT THROMBOSIS -Pharmacotherapy-

18 HORIZONS-STENT THROMBOSIS: 2-year Events Effect of Early Heparin (prerandomization): 1-Day Landmark 7 Pre-Randomization Heparin No Pre-Randomization Heparin Definite/Probable Stent Thrombosis (%) % HR: 0.24 [95% CI: 0.11, 0.52] p = < % HR: 0.77 [95% CI: 0.52, 1.15] p = % 3.3% 0 24h Number at risk P-R Heparin No P-R Heparin Time in Months Dangas GD et al., Circulation 2011 Apr 26;123(16):

19 Clopidogrel Double vs Standard Dose Definite Stent Thrombosis (angio confirmed) Stent thrombosis (%) 1.4% 1.2% 1.0% 0.8% 0.6% 0.4% 0.2% Clopidogrel standard-dose Clopidogrel double-dose Clopidogrel standard dose Clopidogrel double dose Adjusted HR 0.54 ( ) P= % Number at risk Days Mehta S. et al. Lancet Oct 9;376(9748):

20 TRITON-TIMI-38 Definite or probable stent thrombosis in 12,844 pts receiving any stent CLOPIDOGREL PRASUGREL Early stent thrombosis HR 0.41 [ ] P< % Late stent thrombosis HR 0.60 [ ] P= % % % DAYS DAYS Wiviott S.D. et al. Lancet. 2008;371:

21 PLATO Stent Thrombosis Clopidogrel (n=5,649) Ticagrelor (n=5,640) 12 Month EventRate (%) 5 3,8 2,5 1,3 HR(95%CI) = 0.67 ( ) P= ,9 1,3 2,8 HR(95%CI) = 0.75 ( ) P=0.02 2,1 3,6 2,8 HR(95%CI) = 0.77 ( ) P= Definite Definite, probable or possible Wallentin L. et al. NEJM 2009;361:

22 CHAMPION-PHOENIX Stent Thrombosis reduction with Cangrelor Bhatt DL et al., N Engl J Med Apr 4;368(14):

23 IPST in CHAMPION PHOENIX 10,939 pts assessed by a blinded core lab Impact on 30-day mortality Généreux P et al. JACC Vol. 63, No. 7, 2014

24 Mortality Following Stent Thrombosis Occurring In-Hospital versus Out-Of-Hospital: Results from HORIZONS-AMI Mortality according to ARC timing definitions of ST Dangas GD et al; JACC 2012;59(20):1752-9

25 Early Stent Thrombosis and Mortality After Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction A Patient-Level Analysis of 2 Randomized Trials Patient-level pooled analysis from HORIZONS-AMI and EUROMAX 30-day outcomes in 4935 patients undergoing ppci with stent implantation at 188 international sites, randomized to either bivalirudin or UFH±GPI. Among patients with early ST, the propensity-adjusted risk of subsequent mortality within 30 days was determined for patients treated with bivalirudin versus heparin±gpi in a Cox multivariable model, with ST treated as a time-dependent variable; all differing baseline covariates were included in the propensity model. Dangas GD et al. Circulation Cardiovasc Interv. 2016;9:e DOI: /CIRCINTERVENTIONS

26 Time-to-event curves for acute stent thrombosis (within 24 hrs of PCI) with a 4-hr landmark analysis 1,5 1.5 Bivalirudin Heparin ± GPI Log Rank P-Value: < Log Rank P-Value: 0.28 Stent Thrombosis (%) 0, % 0.4% 0,0 0.04% 0.2% Number at risk Time in Hours Bivalirudin Heparin ± GPI Dangas GD et al. Circulation Cardiovasc Interv. 2016;9:e DOI: /CIRCINTERVENTIONS

27 Kaplan Meier estimates of 30-day mortality in patients with stent thrombosis (ST) according to the timing of the ST event and regimen Dangas GD et al. Circulation Cardiovasc Interv. 2016;9:e /CIRCINTERVENTIONS

28 Stent Thrombosis in 2016 and the BVS ERA

29 DAPT Cessation And 2-Year Definite / Probable Stent Thrombosis Mehran R et al; Lancet Nov 23;382(9906):

30 Coronary Thrombosis and Major Bleeding After PCI With Drug-Eluting Stents Numbers of patients at low, intermediate, and high bleeding risk, respectively, with similar proportions observed for the different thrombotic risk categories. Baber U et al., J Am Coll Cardiol May 17;67(19):

31 Predicting Risks for Coronary Thrombosis and Major Bleeding After PCI with DES: Risk Scores from PARIS Registry Integer Risk Score for Major Bleeding Integer Risk Score for Coronary Thrombosis Parameter Score Parameter Score Age, years < > BMI, kg/m 2 < > 35 Current Smoking Yes No +2 0 Diabetes Mellitus Acute Coronary Syndrome Current Smoking None Non-Insulin Insulin No Yes, Tn (-) Yes, Tn (+) Yes No +1 0 Anemia Present Absent +3 0 CKD* CrCl < 60 ml/min/1.73 m2 Present Absent +2 0 CKD* 3ple Therapy on discharge Present Absent +2 0 Yes No +2 0 Prior PCI Prior CABG Yes No +2 0 Yes No +2 0 Baber U et al., J Am Coll Cardiol May 17;67(19):

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33 PCI complexity & Stent thrombosis Complex PCI is strongly associated with increased risk of definite or probable ST with a magnitude that was comparable to that of a history of prior MI or high-risk ACS presentation. Giustino G et al., J Am Coll Cardiol Aug 25. pii: S (16)34935-X

34 ST risk score (UA/nonSTEMI & STEMI) Based on ACUITY & HORIZONS datasets Variable Calculation Integer Assignment for Stent Thrombosis Risk Score Type of Acute Coronary NSTE-ACS w/o NSTE-ACS with ST Syndrome ST changes +1 deviation +2 STEMI+4 Current Smoking Yes: +1 No: +0 Insulin treated diabetes Yes: +2 No: +0 History of PCI Yes: +1 No: +0 Baseline Platelet Count <250K/ul: K/ul-400K/ul: +1 >400K/ul: +2 Absence of pre-pci Heparin Yes: +1 No: 0 Aneurysm or Ulceration Yes: +2 No: 0 Baseline TIMI flow grade 0/1 Yes: +1 No: 0 Final TIMI flow grade < 3 Yes: +1 No: 0 Number of Vessels Treated 1 vessel: +0 2 vessels: +1 3 vessels: +2 Dangas GD et al; JACC Cardiovasc Interv Nov;5(11):

35 Derivation cohort Validation cohort Dangas GD et al., JACC Cardiovasc Interv Nov;5(11):

36 Risk of ST with 1 st - and 2 nd -Generation Drug-Eluting Stents According to Duration of Dual Antiplatelet Therapy Giustino G et al., J Am Coll Cardiol Apr 7;65(13):

37 Timing of strut reabsorption Timing of vascular scaffold reabsorption Indolfi C et al., Nat Rev Cardiol Sep 29. doi: /nrcardio

38 Gregg SW TCT presentation 2016

39 The implantation protocol used was an independent predictor of ScT BVS specific protocol Nitrates Sizing with balloon (1:1:1) 2 angiographic planes Low threshold for OCT Implant following IFU NC postdilation (+0.5mm) Do not accept MLD <2.5/2.9mm* MLA <4.9/6.6mm 2 * *For a mm and 3.5 mm scaffold respectively Puricel S. et al., J Am Coll Cardiol Mar 1;67(8):921-31

40 Timing and Mechanism of DES Thrombosis Early (<30d) Late (1-12 Mo) Very late (>12 Mo) Procedural Delayed healing Abnormal vascular response Underexpansion Uncovered struts Hypersensitivity Edge dissection Fibrin deposition Extensive fibrin deposition Residual plaque Late malapposition? Neoatherosclerosis Nakazawa et al. J Cardiol 2011;58:84-91 Claessen BE Dangas GD; JACC Cardiovasc Interv 2014;7:

41 How to Minimize Stent Thrombosis Better Patient selection Screening for adherence and bleeding risk / ability to tolerate DAPT No upcoming surgical procedures (6 wk for BMS, 6 12 m for DES) Better Stent selection and deployment Consider use of stents with proven lower stent thrombosis rates Appropriate vessel sizing, high-pressure deployment/post-dilation Ensuring absence of edge dissections and adequate inflow/outflow Avoiding the use of 2 stents in bifurcation lesions (if possible) Better Peri- and post-procedure care Use of more potent oral antiplatelet regimens in appropriately indicated clinical scenarios (e.g. ACS with acceptable bleeding risk) Patient education and clinical follow-up are critical Continuation of DAPT without interruption whenever possible Kirtane AJ. et al Circulation Sep 13;124(11):1283-7

42 Prevention of Stent Thrombosis and DAPT 2 nd Generation DES (ZES, EES) With or without potent antiplatelet agents (prasugrel, ticagrelor) Short term DAPT Favors the stronger antiplatelet agents/regimens Is Closely related to type of stent & adherence

43 What are we treating? Vulnerable Stent vs Patient?? c/o Dominic Angiolillo 20-25% risk of falling again in the next 5 years