Stent Thrombosis:

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

• Early lt30 day
• Late 30d 1yr
• V late
• gt1 yr TAXUS
• gt6months CYPHER

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Incidence and Timing BMS

• Registry data BMS angiographic ST
• most early, in hospital or lt10 days
• LST and VLST rare

ST 20/1191 patients (1.6)
Wang CCI 2002
days
lt1
1-30
60
120
180
240
ST 97/6,058 patients (1.6)
Wenaweser EHJ 2005
days
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Outcome

• Nonfatal MI
• approx 80
• Mortality depends on definition, duration FU
• Studies including all sudden deaths
• 20-50 Iakovou, Cutlip
• Patients Rx for angiographic stent thrombosis
• 10-30 6 months Wenaweser, Cutlip, Waksman

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Improved technology
Patient selection

• Stent
• Material
• Polymer
• Drug

• Patient/lesion
• Diameter
• Length
• ACS
• LV function

• Procedure
• Under-expansion
• Dissection
• Thrombus
• Antiplatelet RX

Technique
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Procedural Factors in Stent Thrombosis Bare
Metal Stents
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• 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 DISSECTION

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Stent Thrombosis BMS vs.DES
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Evidence From Randomized Trials

• Relatively Simple Patient and Lesion Subsets

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Taxus vs Endeavor Definition For ST
QWMI Q-wave myocardial infarction NQWMI
nonQ-wave myocardial infarction MI myocardial
infarction STEMI ST-segment elevation
myocardial infarction. 1. Stone et al. N Engl
Med. 2004350221.. 2. Fajadet et al.
Circulation. 2006 11498-806 Endeavor is a
trademark of Medtronic Vascular, Inc.
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Taxus vs Endeavor Definition For ST
Stone et al. N Engl Med. 2004350221..
Fajadet et al. Circulation. 2006 11498-806
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CYPHER - Stent Thrombosis to 9 Months
Meta-analysis of 6 studies (N2074)
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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, gt1 yr) remain problematic until
  more data are available!

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TAXUS - Stent Thrombosis to 9 Months
Meta-analysis of 4 studies (N3445)
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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 gt Control at 6 months
• Overall rate of very late ST is 0.4
• No stent thrombosis in Taxus after 2 years

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How often does it occur in the Real World ?
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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
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2229 Patients Successful DES Implantation
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Predictors of stent thrombosis
At a mean follow-up of 9.3 ? 5.6 months
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Thrombosis rates according to selected patient
characteristics

Aspirin And Clopidogrel Stopped
Prior Brachytherapy
DM
UA
LMS
BIFURC
RENAL FAILURE
Iakovou et al JAMA 2005
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Recent Data ESC 2006

• RAVEL five year follow-up
• Meta-analysis DES Trials- Basel
• Meta-analysis DES Trials- Geneva
• BASKET
• Rotterdam/Zurich Registry

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RAVEL Five Year Follow-Up
Fischers exact test
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Recent Data ESC 2006

• RAVEL five year follow-up
• Meta-analysis DES Trials- Basel
• Meta-analysis DES Trials- Geneva
• BASKET
• Rotterdam/Zurich Registry

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Safety of Drug-Eluting StentsInsights from a
Meta-AnalysisAlain J Nordmann, Matthias Briel,
Heiner C BucherBasel Institute for Clinical
EpidemiologySwitzerland
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Purpose
Meta-analysis of randomised controlled trials
comparing sirolimus-or paclitaxel-eluting stents
to bare metal stents to evaluate their effect on
total, cardiac, and non-cardiac mortality.
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Overall Mortality
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Non-Cardiac Mortality
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Non-Cardiac Deaths (n35) 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
• Alzheimers 1 3
• Road traffic accident 1 3

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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
  cause-specific deaths in patients receiving DES
  are mandatory to determine long-term safety of
  these devices

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Recent Data ESC 2006

• RAVEL five year follow-up
• Meta-analysis DES Trials- Basel
• Meta-analysis DES Trials- Geneva
• BASKET
• Rotterdam/Zurich Registry

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Safety of Drug-Eluting Stents Insights From
Meta-AnalysisE. CamenzindGeneva
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Goal of the Study

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

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BMS vs. SES
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BMS vs. PES
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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

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Recent Data ESC 2006

• RAVEL five year follow-up
• Meta-analysis DES Trials- Basel
• Meta-analysis DES Trials- Basel
• BASKET
• Rotterdam/Zurich Registry

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BASKET 18 Month Results (n826)
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Recent Data ESC 2006

• RAVEL five year follow-up
• Meta-analysis DES Trials- Basel
• Meta-analysis DES Trials- Geneva
• BASKET
• Rotterdam/Zurich Registry

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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 SerruysBern and
Rotterdam
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Ong et al, JACC 2005
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Angiographically Proven Stent Thrombosis
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Stent Thrombosis Rate, Time, SES vs. PES

• April 2002 - December 2005
• 8668 pts PCI with DES only
• SES n3817
• PES n4851
• Angiographically documented ST
• 1.8 (N157/8668), SESPES
• Early (median 4, range 0-28) 59 cases
• Late (median 453, range 31-1074) 41 cases

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Differences Between Early and Late ST Cohorts

• Not on dual antiplatelet therapy
• 11 early ST patients
• 75 late ST pts (plt0.001)
• Premature discontinuation of either aspirin or
  plavix
• 6 early ST patients
• 22 late ST patients (p0.004)
• CAD risk factors more often encountered in late
  ST patients
• Continued smoking (plt0.0001)
• Hypertension (0.003)
• Hyperlipidaemia (0.004)
• Early ST Patients had (vs. Late ST patients)
• Smaller final MLD 2.39 vs. 2.57 mm ( p0.03)
• Greater residual diameter stenosis 18 vs. 13
  (p0.04)

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Angiographically Proven ST RotterdamZurich
Incremental rate of 0.6 per year
ST
SESPES
Days
Pts at risk
6349 6173 6042 4556 3083 865 0
1.3 1.5 2.0 2.6 3.3
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Late Stent Thrombosis Mechanisms?

• Delayed healing?
• Abnormal endothelium?
• Hypersensitivity to polymer?
• Neointimal regression?
• Acquired aneurysm formation?

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All Plausible Mechanisms- but

• LST fortunately relatively rare
• Overlapping stents common
• Endothelial dysfunction ubiquitous
• Denominator unknown
• Analogous to the VP conundrum

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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

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Pre Post Six Months Three Years
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IVUS Crosssections-Bare Cypher
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LAD Three Overlapping Covered Stents
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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?

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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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