Stent Thrombosis: Patient, Procedural, and Stent Factors. Eugene Mc Fadden Cork, Ireland

Transcription

1 Stent Thrombosis: Patient, Procedural, and Stent Factors Eugene Mc Fadden Cork, Ireland

2 Definitions Early <30 day Late 30d 1yr V late >1 yr TAXUS >6months CYPHER

3 Incidence and Timing BMS Registry data BMS angiographic ST 10 most early, in hospital or <10 days LST and VLST rare 8 6 ST 20/1191 patients (1.6%) Wang CCI < ST 97/6,058 patients (1.6%) Wenaweser EHJ 2005 days days

4 Outcome Nonfatal MI approx 80% Mortality depends on definition, duration FU Studies including all sudden deaths % Iakovou, Cutlip Patients Rx for angiographic stent thrombosis % 6 months Wenaweser, Cutlip, Waksman

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6 Improved technology Patient selection Stent - Material - Polymer - Drug Patient/lesion - Diameter - Length - ACS - LV function Procedure - Underexpansion - Dissection - Thrombus - Antiplatelet RX Technique

7 Procedural Factors in Stent Thrombosis: Bare Metal Stents Cutlip et al, Circulation 2001 Orford et al, JACC 2002 Cheneau et al, Circulation 2003 Follow-up time 30 days 30 days 7 days Diagnosis Angio + clinical Angiographic Angiographic No. of Patients 6186 pts (6219 vessels) 4509 pts 7484 pts Incidence 53 pts (0.9%) 23 pts (0.51%) 27 pts (0.36%) Risk factors 1. Persistent dissection 2. Stent Length >25mm 1. Number of stents placed 1. Inadequate expansion 2. Residual dissection 3. Final lumen diameter <3.0mm

8 54F CRF on CAPD; DM Rx: RCA prox direct stented 3.0x32mm LAD/diag crush with kiss 2.75x32 / 2.25x24mm LAD dist edge 2.25x12 LAD prox edge 3.0x8 Abciximab intraproc Day 6 Ant ST elevation Died before reaching cath lab Not taking ASA, only clopidogrel Dx: NO ASA, RESIDUAL

9 Stent Thrombosis: BMS vs.des

10 Evidence From Randomized Trials Relatively Simple Patient and Lesion Subsets

11 Taxus vs Endeavor Definition For ST TAXUS 1 Stent Endeavor Stent ACS with angiographic documentation ACS with angiographic documentation Or Or Acute MI in the distribution of the treated vessel Acute MI in the distribution of the treated vessel Or Or Death from cardiac causes within 30 days Death resulting from cardiac causes within 30 days QWMI = Q-wave myocardial infarction; NQWMI = non Q-wave myocardial infarction; MI = myocardial infarction; STEMI = ST-segment elevation myocardial infarction. 1. Stone et al. N Engl Med. 2004;350: Fajadet et al. Circulation. 2006; 114: Endeavor is a trademark of Medtronic Vascular, Inc.

12 Taxus vs Endeavor Definition For ST Stone et al. N Engl Med. 2004;350:221.. Fajadet et al. Circulation. 2006; 114:98-806

13 CYPHER - Stent Thrombosis to 9 Months Meta-analysis of 6 studies (N=2074) Stent Thrombosis % (n) Control (N=870) CYPHER (N=1204) P Acute 0.0% (0) 0.1% (1) 0.99 Subacute 0.1% (1) 0.3% (4) 0.41 Late (>28 days) 0.5% (4) 0.2% (2) 0.25 Total 0.58% (5) 0.58% (7) 0.68

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17 Conclusions No significant difference, between SES and BMS, in either early or late ST events. However, there are soft signals of increased ST with Cypher, including 4 vs. 0 ST events between 1-3 years (~0.5%). Larger studies in more complex lesions are definitely required to determine differences vs. BMS or other DES. Extended antiplatelet RX recommendations (? 6 months, 1 yr, >1 yr) remain problematic until more data are available!

18 TAXUS - Stent Thrombosis to 9 Months Meta-analysis of 4 studies (N=3445) Stent Thrombosis %(n) Control (N=1727) TAXUS (N=1718) P In-hospital 0.2% (4) 0.2% (3) 1.00 Out of hospital To 1 Month 0.4% (7) 0.3% (5) to 6 Months 0.1% (2) 0.1% (2) to 9 Months 0.0% (0) 0.0% (0) - Total 0.75% (13) 0.58% (10) 0.68

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23 Conclusions Early Stent Thrombosis Accounts for 57% of total stent thrombosis Distribution similar in Taxus and Control suggesting peri-procedural causes Late Stent Thrombosis Taxus > Control at 6 months Overall rate of very late ST is ~0.4% No stent thrombosis in Taxus after 2 years

24 How often does it occur in the Real World?

25 Late Stent Thrombosis 2229 pts (SES 1062, PES 1167) Definition of stent thrombosis: Acute clinical event + angiographic proof OR Sudden cardiac death not attributable to another lesion. Follow-up: 9 months Iakovou J, Colombo A, JAMA 2005

26 2229 Patients: Successful DES Implantation CYPHER N=1062 TAXUS N=1167 P Subacute Thrombosis 0.4% (4) 0.8% (9) 0.5 Late (>28 days) Thrombosis 0.5% (5) 0.8% (9) 0.3 Overall Thrombosis 0.9% (9) 1.6% (18) 0.2

27 Thrombosis rates according to selected patient characteristics % 29 Aspirin And Clopidogrel Stopped Prior Brachytherapy RENAL FAILURE BIFURC LMS DM UA *Iakovou et al JAMA 2005

28 Recent Data ESC 2006 RAVEL five year follow-up Meta-analysis DES Trials- Basel Meta-analysis DES Trials- Geneva BASKET Rotterdam/Zurich Registry

29 RAVEL Five Year Follow-Up End point (%) Freedom from death Freedom from death/mi Freedom from TLR Freedom from MACE (death, MI, TLR) Sirolimuseluting stent Bare-metal stent P* *Fischer s exact test

30 Recent Data ESC 2006 RAVEL five year follow-up Meta-analysis DES Trials- Basel Meta-analysis DES Trials- Geneva BASKET Rotterdam/Zurich Registry

31 Safety of Drug-Eluting Stents: Insights from a Meta-Analysis Alain J Nordmann, Matthias Briel, Heiner C Bucher Basel Institute for Clinical Epidemiology Switzerland

32 Purpose Meta-analysis of randomised controlled trials comparing sirolimus-or paclitaxeleluting stents to bare metal stents to evaluate their effect on total, cardiac, and non-cardiac mortality.

33 Overall Mortality

34 Non-Cardiac Mortality

35 Non-Cardiac Deaths (n=35) in 7 SES Trials Ravel, Sirius, C + E-Sirius, SES Smart, Diabetes, Basket Cancer 15 43% Stroke 6 17% Sepsis 6 17% Respiratory failure 4 11% Pulmonary embolism 2 6% Alzheimer s 1 3% Road traffic accident 1 3%

36 Conclusions DES for the treatment of coronary artery disease do not reduce total mortality when compared to BMS Preliminary evidence suggests that sirolimus-, but not paclitaxel-eluting stents, may lead to increased non-cardiac mortality Long term follow-up and assessment of causespecific deaths in patients receiving DES are mandatory to determine long-term safety of these devices

37 Recent Data ESC 2006 RAVEL five year follow-up Meta-analysis DES Trials- Basel Meta-analysis DES Trials- Geneva BASKET Rotterdam/Zurich Registry

38 Safety of Drug-Eluting Stents: Insights From Meta-Analysis E. Camenzind Geneva

39 Goal of the Study To evaluate, in a metaanalysis, the effect of the use of BMS compared to DES (SES or PES) on the longterm rate of death or Q-wave MI Data from RAVEL, SIRIUS, E- and C-SIRIUS, TAXUS I, II, IV, V, VI

40 BMS vs. SES Endpoint Death/QMI BMS (n=870) SES (n=878) 6-9 months 0.9% 1.7% year 1.4% 2.3% years 2.0% 3.7% years 4.0% 6.0% 0.06 Last FUP 3.9% 6.3% 0.03 P R R 1.38

41 BMS vs. PES Endpoint Death/QMI BMS n=1675 PES n= months 1.5% 1.6% year 1.6% 1.7% years 2.8% 2.6% years 3.1% 3.5% 0.60 Last FUP 2.6% 2.3% 0.68 P R R 1.16

42 Conclusions Treatment with SES was associated with a significant increase in death/qmi at 3 years compared with BMS Death or QMI did not differ between PES and BMS The present meta-analysis shows a significant increase in death/qmi with SES compared to BMS and mandates further long term follow-up of patients receiving DES

43 Recent Data ESC 2006 RAVEL five year follow-up Meta-analysis DES Trials- Basel Meta-analysis DES Trials- Basel BASKET Rotterdam/Zurich Registry

44 BASKET 18 Month Results (n=826) Endpoint (%) BMS DES P PES or SES Death/MI Noninfarct TVR MACE

45 Recent Data ESC 2006 RAVEL five year follow-up Meta-analysis DES Trials- Basel Meta-analysis DES Trials- Geneva BASKET Rotterdam/Zurich Registry

46 Late Stent thrombosis Following Drug- Eluting Stent Implantation: Data From a Large, Two-institutional Cohort Study P. Wenaweser, K. Tsuchida, S. Vaina, L. Abrecht, J. Daemen, C. Morger, S. Windecker, PW Serruys Bern and Rotterdam

47 Ong et al, JACC 2005

48 Angiographically Proven Stent Thrombosis

49 Stent Thrombosis: Rate, Time, SES vs. PES April December pts PCI with DES only SES: n=3817 PES: n=4851 Angiographically documented ST 1.8% (N=157/8668), SES=PES Early (median 4, range 0-28) 59% cases Late (median 453, range ) 41% cases

50 Differences Between Early and Late ST Cohorts Not on dual antiplatelet therapy 11% early ST patients 75% late ST pts (p<0.001) Premature discontinuation of either aspirin or plavix 6% early ST patients 22% late ST patients (p=0.004) CAD risk factors more often encountered in late ST patients Continued smoking (p<0.0001) Hypertension (0.003) Hyperlipidaemia (0.004) Early ST Patients had (vs. Late ST patients) Smaller final MLD 2.39: vs mm ( p=0.03) Greater residual diameter stenosis 18 vs. 13% (p=0.04)

51 Angiographically Proven ST: Rotterdam+Zurich Incremental rate of 0.6% per year 5 4 % ST 3 2 SES+PES 1 Days Pts at risk % 1.3% 1.5% 2.0% 2.6% 3.3%

52 Late Stent Thrombosis: Mechanisms? Delayed healing? Abnormal endothelium? Hypersensitivity to polymer? Neointimal regression? Acquired aneurysm formation?

53 All Plausible Mechanisms- but LST fortunately relatively rare Overlapping stents common Endothelial dysfunction ubiquitous Denominator unknown Analogous to the VP conundrum

54 Late Acquired Aneurysm Formation 50 years, woman, Anterior MI 2/2002 Staged intervention: LAD 3/2002, RCA 4/2002 LAD CYPHER, RCA CYPHER + BARE RESEARCH Control angio 6 months Elective surgery 3/2005 Aspirin stopped Anterior MI 3 days later, cardiogenic shock LAD stent occlusion

55 Pre Post Six Months Three Years

56 IVUS Crosssections-Bare & Cypher

57 LAD Three Overlapping Covered Stents

58 Take Home Messages Early ST accounts for 60% of ST with DES Ensure intervention justified and that the patient informed of risks Keep interventions simple especially in patients with high-risk features Optimise the result-postdilate, kiss Compliance with antiplatelet therapy Disseminate information on antiplatelet RX to non-cardiologists More liberal BMS use?

59 Take Home Messages LST is a reality Longer dual antiplatelet therapy? More long-term studies (IVUS)? Trends for increased mortality need to be elucidated

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