1. 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 2009 San Francisco

2. No Conflicts

3. 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 outcomes of STEMI due to ST with STEMI due to de novo coronary artery occlusion treated with primary PCI.

4. 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).

5. 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-elevation of the cardiac enzymes or documented IRA re-occlusion Urgent Target Vessel Revascularization: Revascularization of the target vessel (PCI or CABG) for recurrent ischemia

6. 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.

7. 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.

8. 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.

9. STEMI due to Stent Thrombosis: Frequency by Year Number Patients % Year 5 13 23 26 34 36 19 11 12 7 23 24 12.4% DES Introduced

10. Baseline Clinical Variables Stent De Novo Thrombosis Occlusion (n = 137) (n = 1551)p value Age > 70 years18.2%24.8%0.08 Male82.5% 67.6%0.0003 Diabetes (any)18.2%16.0%0.49 Hypertension69.3%45.9% <0.0001 Smoker (current)54.7%49.3%0.22 Prior MI56.2%11.9% <0.0001 Prior CABG11.7% 4.8% 0.0006 Anterior MI41.6%35.8%0.17 Cardiogenic Shock16.1%6.8% <0.0001

11. Angiographic and Procedural Variables Stent De Novo Thrombosis Occlusion (n = 137) (n = 1551) p value 3 Vessel CAD21.9%25.1%0.40 LVEF < 40%31.4%20.1%0.002 TIMI Flow 2-3 Pre-PCI 10.3%25.8% <0.0001 GP IIb/IIIa Used80.3%73.5%0.082 Stent Used46.7%80.5% <0.0001 TIMI 3 Flow Post-PCI93.4%98.1%0.047 PCI Success93.4%97.6%0.004

12. In-Hospital Outcomes Stent Thrombosis vs De Novo Occlusion

13. In-Hospital Death or Re-infarction Stent Thrombosis versus De Novo Occlusion Stent Thrombosis De Novo Occlusion 8.1% 14.8% log rank p value = 0.0007 Death or Re-infarction % Days 5 15 20 25 10 0 123456789 1112131415

14. Multivariable Predictors of In-hospital Reinfarction 6.6 4.9 Stent Thrombosis CHF 0.11 10 Log Odds Ratio (95% CI)

15. Multivariable Predictors of In-Hospital Death or Reinfarction Cardiogenic Shock CHF CPR Age > 70 years Stent Thrombosis 5.1 3.9 2.3 2.1 0.1110 Log Odds Ratio (95% CI)

16. Late Cardiac Mortality Stent Thrombosis versus De Novo Occlusion Years Cardiac Mortality % De Novo Occlusion Stent Thrombosis log rank p value = 0.0016 5 15 20 25 10 0 123 20.3% 11.3%

17. Comparisons of BMS and DES

18. Off-Label Indications at Original Stent Implant BMS DES p value (n=81) (n=54) STEMI54.3% 37.0% 0.08 Multi-lesion PCI29.6% 29.6% 0.85 Overlapping stents19.8% 18.5% 0.96 Long lesions (>28)16.0% 22.2% 0.50 Multi-vessel PCI 4.9% 16.7% 0.02 Ostial lesions 3.7% 11.1% 0.07 SVG 8.6% 0.0% 0.07 In-stent restenosis 2.5% 7.4% 0.14 Bifurcation lesions 3.7% 3.7% 0.35 Any Off Label86.4% 87.0% 0.88

19. Time to Stent Thrombosis Off Clopidogrel at Time of ST < 1 Year:BMS53% DES54%  1 Year:BMS76% DES89% 26% Very Late 48% Very Late

20. Adjunctive Treatment of Stent Thrombosis and Procedural Results BMS DES p value (n=81) (n=54) GP IIb/IIIa Inhibitor 77.8% 81.5%0.76 Thrombectomy Aspiration 22.8% 63.0%0.0001 Rheolytic 12.3% 9.3%0.19 Any 32.1% 68.5%0.0001 IVUS 29.6% 53.7%0.009 New Stent 44.4% 46.3%0.97 TIMI 3 Flow post-PCI 96.3% 94.5%0.62 Procedural Success 95.1% 91.1%0.35

21. In-Hospital Outcomes in Patients with ST BMS vs DES BMS DES p value (n=81) (n=54) Death 8.6% 8.9%0.95 Re-infarction 3.7% 8.9%0.20 Urgent TVR 3.7% 7.1%0.37 Death/Re-MI12.3% 16.1%0.54

22. 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.

23. 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.

24. 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.

25. 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.

26. 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.

30. Cardiac Death Stent Thrombosis versus De Novo Occlusion Years Cardiac Death % De Novo Occlusion Stent Thrombosis log rank p value = 0.0016 5 15 20 25 10 0 123 30 456 27.5% 15.5%

31. 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.