STEMI Due to Stent Thrombosis: An Enlarging Subgroup of High Risk Patients

Bruce Brodie, Adam Bensimhon, Nathan Fleishman, Charles Hansen, Mike Cooper, Henry Smith, John Edmunds,

Jay Varanasi and Tom Stuckey LeBauer Cardiovascular Research Foundation

Greensboro, NC

TCT 2009San Francisco

No Conflicts

Background and Purpose

Early and late stent thrombosis (ST) is a major complication following PCI with stenting and is associated with a high incidence of myocardial infarction and death. ST elevation myocardial infarction (STEMI) is often a consequence of stent thrombosis and is usually treated with repeat PCI. The frequency of STEMI due to ST and outcomes of STEMI due to ST treated with primary PCI have not been well documented.

The purpose of this study is to evaluate the changing frequency of STEMI due to ST and to compare outcomesof STEMI due to ST with STEMI due to de novo coronary artery occlusion treated with primary PCI.

Study Population• Our study population consists of consecutive patients with STEMI treated with primary PCI at our institution by our study group from 1997-2008 (N = 1,688).

a) Primary PCI has been used almost exclusively at our institution since 1984.

b) STEMI was defined as AMI with STE > 1mm in > 2 contiguous leads or LBBB. Patients with prior fibrinolytic therapy were excluded.

• Patients with STEMI due to stent thrombosis (N = 137) were compared with patients with STEMI due to de novo coronary artery occlusion (N = 1,551).

Definitions• STEMI due to stent thrombosis:

STEMI with angiographically documented thrombotic occlusion within the stent in the IRA

• Re-infarction:Recurrent ischemic symptoms with re-elevationof the cardiac enzymes or documented IRAre-occlusion

• Urgent Target Vessel Revascularization:Revascularization of the target vessel (PCI orCABG) for recurrent ischemia

Treatment Protocol

• All patients received ASA 325 mg

• Ticlopidine or clopidogrel were standard in all stented pts and in recent years clopidogrel has been given prior to PCI as standard treatment.

• UFH and GP IIb/IIIa platelet inhibitors were standard treatment in the early years of the study, but recently bivalirudin with bail-out GP IIb/IIIa inhibitors has become standard treatment. • In patients with stent thrombosis -- GP IIb/IIIa inhibitors, adjunctive thrombectomy, and additional stents were used at the discretion of the operator.

Data Collection

• Patients were identified prospectively and enrolled in our ongoing database of consecutive primary PCI pts.

• Angiographic and procedural data were entered at the time of the procedure by the investigators. In-hospital data were entered by clinical coordinators from chart reviews. Post-hospital follow-up data were obtained from EMR reviews and phone contact. Deaths were also sought through the social security index.

• Identification of all cases of STEMI due to stent thrombosis and all major adverse events were adjudicated by principal investigators.

Statistical Methods

• Comparisons of categorical variables were performed with chi-square or Fisher’s exact test.

• Multivariable analyses of predictor variables of in-hospital outcomes were performed with logistical regression

• Kaplan-Meier event curves were constructed and comparisons between patients with stent thrombosis and de novo occlusion were made with log rank tests.

STEMI due to Stent Thrombosis: Frequency by Year

0

5

10

15

20

25

30

35

40

97-98 99-00 01-02 03-04 05-06 07-08

BMS(n=81)DES(n=54)

Nu

mb

er P

atie

nts

%

Year

5

13

2326

3436

19

1112

7

23 24

12.4%

DES Introduced

Baseline Clinical Variables

Stent De Novo Thrombosis Occlusion (n = 137) (n = 1551) p value

Age > 70 years 18.2% 24.8% 0.08Male 82.5% 67.6% 0.0003Diabetes (any) 18.2% 16.0% 0.49Hypertension 69.3% 45.9% <0.0001Smoker (current) 54.7% 49.3% 0.22Prior MI 56.2% 11.9% <0.0001Prior CABG 11.7% 4.8% 0.0006Anterior MI 41.6% 35.8% 0.17Cardiogenic Shock 16.1% 6.8% <0.0001

Angiographic and Procedural Variables

Stent De Novo Thrombosis Occlusion (n = 137) (n = 1551) p value

3 Vessel CAD 21.9% 25.1% 0.40LVEF < 40% 31.4% 20.1% 0.002TIMI Flow 2-3 Pre-PCI 10.3% 25.8% <0.0001

GP IIb/IIIa Used 80.3% 73.5% 0.082Stent Used 46.7% 80.5% <0.0001TIMI 3 Flow Post-PCI 93.4% 98.1% 0.047 PCI Success 93.4% 97.6% 0.004

In-Hospital OutcomesStent Thrombosis vs De Novo Occlusion

In-Hospital Death or Re-infarctionStent Thrombosis versus De Novo Occlusion

Stent Thrombosis

De Novo Occlusion8.1%

14.8%

log rank p value = 0.0007

Dea

th o

r R

e-in

farc

tion

%

Days

5

15

20

25

10

01 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Multivariable Predictors ofIn-hospital Reinfarction

6.6

4.9Stent Thrombosis

CHF

0.1 1 10Log Odds Ratio (95% CI)

Multivariable Predictors ofIn-Hospital Death or Reinfarction

Cardiogenic Shock

CHF

CPR

Age > 70 years

Stent Thrombosis

5.1

3.9

2.3

2.1

2.1

0.1 1 10

Log Odds Ratio (95% CI)

Late Cardiac MortalityStent Thrombosis versus De Novo Occlusion

Years

Car

diac

Mor

talit

y %

De Novo Occlusion

Stent Thrombosis

log rank p value = 0.00165

15

20

25

10

01 2 3

20.3%

11.3%

Comparisons of BMS and DES

Off-Label Indications at Original Stent Implant

BMS DES p value(n=81) (n=54)

STEMI 54.3% 37.0% 0.08Multi-lesion PCI 29.6% 29.6% 0.85Overlapping stents 19.8% 18.5% 0.96Long lesions (>28) 16.0% 22.2% 0.50Multi-vessel PCI 4.9% 16.7% 0.02Ostial lesions 3.7% 11.1% 0.07SVG 8.6% 0.0% 0.07In-stent restenosis 2.5% 7.4% 0.14Bifurcation lesions 3.7% 3.7% 0.35

Any Off Label 86.4% 87.0% 0.88

Time to Stent Thrombosis

Off Clopidogrel at Time of ST< 1 Year: BMS 53%

DES 54%1 Year: BMS 76%

DES 89%

26% Very Late

48% Very Late

Adjunctive Treatment of Stent Thrombosisand Procedural Results

BMS DES p value (n=81) (n=54)

GP IIb/IIIa Inhibitor 77.8% 81.5% 0.76Thrombectomy

Aspiration 22.8% 63.0% 0.0001Rheolytic 12.3% 9.3% 0.19Any 32.1% 68.5% 0.0001

IVUS 29.6% 53.7% 0.009New Stent 44.4% 46.3% 0.97

TIMI 3 Flow post-PCI 96.3% 94.5% 0.62Procedural Success 95.1% 91.1% 0.35

In-Hospital Outcomes in Patients with STBMS vs DES

BMS DES p value (n=81) (n=54)

Death 8.6% 8.9% 0.95Re-infarction 3.7% 8.9% 0.20Urgent TVR 3.7% 7.1% 0.37Death/Re-MI 12.3% 16.1% 0.54

Conclusions

• Stent thrombosis accounts for in increasing proportion of STEMI patients treated with primary PCI. (now about 12%)

• The great majority (87%) of original stent implants (both BMS and DES) were performed for “off-label” use and almost half (47%) were implanted initially for STEMI.

• Patients with STEMI due to stent thrombosis have higher baseline risk compared with de novo occlusion --- a higher frequency of prior MI, prior CABG and shock and lower EF and lower frequency of TIMI 2-3 flow pre-PCI.

Conclusions (cont)

• Patients with STEMI due to stent thrombosis have worse procedural outcomes --- less TIMI 3 flow post-PCI and lower procedural success.

• Patients with STEMI due to ST have a higher frequency of in-hospital death or re-infarction and a higher frequency of late cardiac mortality

• STEMI due to ST remains an independent predictor of in-hospital re-infarction and death or re-infarction after adjustments for baseline clinical risk.

Limitations

• This is an observational registry. The population of stented pts at risk for STEMI due to ST is not known. Consequently, we cannot assess the risk of STEMI due to ST in stented patients, and we cannot assess the relative risks of STEMI due to ST in patients treated with DES versus BMS.

• We have late survival data, but we don’t have data for post- hospital re-infarction and stent thrombosis which are important endpoints in patients with STEMI due to ST.

Clinical Implications

• It is clear from our data that STEMI due to stent thrombosis represents an enlarging population of STEMI patients with poor outcomes.

• Efforts to prevent this problem are most important. These may include the development of new stents with lower risk of stent thrombosis, improved techniques for stent deployment and improved anti-platelet therapies. Since so many of these patients had the original stent implanted for “off-label” use and especially for STEMI, new PCI strategies may be needed in these subgroups.

Clinical Implications (cont)

• Since procedural results in patients with STEMI due to stent thrombosis are suboptimal, new methods are needed to improve procedural results.

• Since death and re-infarction and recurrent stent thrombosis are frequent after STEMI due to ST, new treatment strategies are needed post-PCI. These might include new and intensive anti-platelet therapies and prophylactic revascularization with CABG.

Cardiac DeathStent Thrombosis versus De Novo Occlusion

Years

Car

diac

Dea

th %

De Novo Occlusion

Stent Thrombosis

log rank p value = 0.00165

15

20

25

10

01 2 3

30

4 5 6

27.5%

15.5%

Conclusions

• Stent thrombosis accounts for in increasing proportion of STEMI patients treated with primary PCI.

• Patients with STEMI due to stent thrombosis have higher baseline risk compared with de novo occlusion --- a higher frequency of prior MI, prior CABG and shock and lower EF and lower frequency of TIMI 2-3 flow pre-PCI.

• Patients with STEMI due to stent thrombosis have worse procedural outcomes --- less TIMI 3 flow post-PCI and lower procedural success.