Jiro Aoki, MD, Gregg W' Stone, MD, Roxana Mehran, MD, Jeffery Moses, MD, Michel E' Bertrand, MD, A'

1
Subacute Stent Thrombosis in Patients with Acute
Coronary Syndromes Treated with Bare Metal and
Drug-Eluting Stents The ACUITY Trial

• Jiro Aoki, MD, Gregg W. Stone, MD, Roxana Mehran,
  MD, Jeffery Moses, MD, Michel E. Bertrand, MD, A.
  Michael Lincoff, MD, E. Magnus Ohman, MD, Harvey
  D. White, DSc, Helen Parise ScD, Martin B. Leon,
  MD, Alexandra J. Lansky, MD

Columbia University Medical Center Cardiovascular
Research Foundation New York City
2
Disclosures

• J. Aoki, J. Moses, H. Parise, M.B. Leon
• None
• G.W. Stone, E. Ohman
• Consultant and advisory board from the Medicines
  Company
• R. Mehran
• Research grant and speakers bureau from the
  Medicines Company
• H.D. White
• Research grant and honoraria from the Medicines
  Company
• A. Lincoff, A. Lansky
• Research grant from the Medicines Company
• M.E. Bertrand
• Honoraria from Nycomed

3
DES use in patients with ACS
The Scottish Coronary Revascularization Register
Steering Group (N13647)
The CRUSADE Initiative (N8832)


2004
2005
2006
2007
2003
2004
Austin D et al. Am Heart J. 2007 in press
Kandzari DE et al. Am J Cardiol. 200596 750-755
4
Backgrounds

• Although the thrombogenic and inflammatory
  coronary milieu in patients with ACS has raised
  concerns of an increased risk of stent
  thrombosis, DES are widely used in patients with
  ACS in daily practice, despite the widely
  recognized delayed rate and extent of
  endothelialization.
• Nonetheless, the incidence and predictors of
  stent thrombosis, including clinical and
  angiographic characteristics and procedural
  outcomes, the relative risk of stent thrombosis
  with BMS and DES, and the impact of antiplatelet
  therapy adherence, have never been investigated
  in these high-risk patients.

5
ACUITY - Study Design
Moderate and high risk unstable angina or NSTEMI
undergoing an invasive strategy (N 13,819)
33
Moderate and high risk ACS (n13,819)
56
Aspirin in all Clopidogrel dosing and timing per
local practice
11
Stratified by pre-angiography thienopyridine use
or administration
G.W.Stone et al. N Engl J Med. 20063552203-16
6
Patient Population This Study
3405 patients with QCA who underwent coronary
stenting in the ACUITY
Medical management
QCA (-) (3757 pts)
PCI without stent (627 pts)
PCI (7789 pts)
QCA () (3405 pts) (4616 lesions)
Stent implanted (7162 pts)
CABG
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Stent Thrombosis Definition
 

• Definite stent thrombosis
• Angiographic confirmation of stent thrombosis
• The presence of a thrombus that originates
  in the stent or in the segment 5 mm proximal or
  distal to the stent and presence of at least 1 of
  the following criteria within a 48-hour time
  window
• Acute onset of ischemic symptoms at rest
• New ischemic ECG changes that suggest
  acute ischemia
• Typical rise and fall in cardiac
  biomarkers (refer to definition of spontaneous
  MI)
• Pathological confirmation of stent thrombosis
• Probable stent thrombosis
• Clinical definition of probable stent
  thrombosis is considered to have occurred after
  intracoronary stenting in the following cases
• Any unexplained death within the first 30
  days
• Irrespective of the time after the index
  procedure, any MI that is related to
• documented acute ischemia in the
  territory of the implanted stent without
• angiographic confirmation of stent
  thrombosis and in the absence of any other
• obvious cause

Cutlip DE et al. Circulation. 20071152344-51
8
Incidence of Subacute Stent Thrombosis

48/3043
16/3043
32/3043
9
Incidence of Subacute Stent Thrombosis
Stent
Anticoagulation
P0.37
P0.96


P0.26
43/3043
5/362
12/1112
19/1165
17/1128
10
Occurrence and Frequency of Stent Thrombosis From
Day 0 To 30
STh occurred at a median of 5 days after
implantation (IQR 1.5-8 days)
Number of patients
Days
11
Thirty-day Clinical Outcomes in Patients With
and Without STh
Plt0.0001

Plt0.0001
Plt0.0001
Plt0.0001
Plt0.0001
P0.02
12
Baseline Clinical Characteristics in Patients
With and Without STh
13
Baseline QCA Parameters in Patients With and
Without STh (1)
 
14
Baseline QCA parameters in Patients With and
Without STh (2)
 
15
Baseline Core Laboratory Measures of the Extent
of Coronary Atherosclerosis
 
16
Procedural Related Factors and Intraprocedural
Adverse Events
 
17
Final Core Laboratory Angiographic Parameters
(Target Vessel)
 
18
Final Core Laboratory Angiographic Parameters
(Target Lesion)
 
19
Relationship Between Antiplatelet Medication Use
(Aspirin) and Stent Thrombosis
 
p0.87
p0.83
p0.10
plt0.0001


In-hospital
Compliance with aspirin administration on gt50
of days after hospital discharge
20
Relationship Between Antiplatelet Medication Use
(Theinopyridines ) and Stent Thrombosis
 
p0.11
p0.02
p1.00
plt0.0001


In-hospital
Compliance with aspirin administration on lt50
of days after hospital discharge
21
Predictors of Definite/Probable Stent
Thrombosis (Patient Level Analysis)
22
Predictors of Definite Stent Thrombosis (Lesion
Level Analysis)
23
Conclusions
 

• Subacute STh is relatively common in these
  high-risk patients, though the risk of STh was
  similar in patients treated with DES and BMS, and
  independent of randomization to heparin plus GP
  IIb/IIIa inhibitors or bivalirudin with or
  without IIb/IIIa inhibitors.
• Subacute STh in patients with ACS is associated
  with a high rate of death, MI and need for repeat
  revascularization.

24
Conclusions
 

• The strongest correlates of subacute definite STh
  in patients with ACS are final stent MLD,
  pre-procedural thienopyridine administration ,
  extent of disease per patient, and baseline
  hemoglobin level.
• Patients with subacute stent thrombosis was
  associated with non compliance with antiplatelet
  drugs within 30 days after hospital discharge.

25
Conclusions
 

• If PCI with BMS or DES implantation is chosen,
  procedural objectives should include minimizing
  the residual stenosis, substantial antiplatelet
  treatment before the procedure, and screening for
  and discussing potential antiplatelet
  non-compliance issues before rather than after
  intervention.
• These simple strategies can be expected to have a
  direct impact on minimizing early STh rates and
  associated major adverse cardiovascular events.