1. A Pharmaco-invasive Reperfusion Strategy with Immediate Percutaneous Coronary Intervention is Safe and Effective in ST-Elevation Myocardial Infarction Patients with Expected Delays Due to Long Distance Transfer David M. Larson, Chris Solie,Scott Sharkey,Sue Duval, Steven Mulder, Joan Krikava, Timothy Dirks, Peter Stokman, James Madison,Barbara Unger, James Harris, Robert Westin, Debra Nyquist, Timothy Henry

2. Background Primary PCI is the preferred reperfusion strategy for STEMI patients if it can be done in a timely manner Only 25% of hospitals in the US are capable of Primary PCI 82% of STEMI patients transferred from non-PCI hospitals for Primary PCI have Door to Balloon times > 120 minutes (ACC/NCDR) Chakrabarti, JACC 2008

3. Reperfusion Options for Patients with Expected Delays 1)Full-dose fibrinolytic, admission to non-PCI hospital with ischemia guided transfer for rescue PCI 2)Full-dose fibrinolytic, routine transfer to PCI hospital with aggressive rescue PCI 3)Primary PCI (no matter how long it takes) 4)Full or reduced dose fibrinolytic with transfer for immediate PCI (Pharmaco-invasive strategy) 5)Any of the above depending on the PCI facility and Cardiologist on call

4. Current Guidelines for STEMI Patients With Expected Delays to PCI Fibrinolysis Recommended if: ACC/AHAESC First Medical Contact (Door) to balloon > 90 minutes> 120 minutes

5. Unresolved Issues Timing of PCI following fibrinolysis Optimal pharmacologic regimen

6. Study Objective Assess the safety and efficacy of a pharmaco-invasive approach utilizing half dose fibrinolytic, Clopidogrel (600mg), UFH and ASA combined with transfer for immediate PCI in patients transferred from rural hospitals located long distances from a PCI center

7. Prospective registry data from the “Level 1 MI” program of the Minneapolis Heart Institute at Abbott Northwestern Hospital (ANW) Included all STEMI patients from 4/03 to 12/08, presenting directly to the PCI hospital (ANW) or transferred from 30 community hospitals No exclusions for age, cardiac arrest or cardiogenic shock Methods

8. PPCI Ph-Inv Primary PCI protocol (Zone 1 < 60 miles) Aspirin 324mg Clopidogrel 600mg UFH 60/kg load, 12/kg/hr infusion Metoprolol 25mg PO Ph-Inv PCI protocol (Zone 2: 60-210 miles) Aspirin 324mg PO Clopidogrel 600mg PO UFH 60/kg load, 12/kg/hr infusion Metoprolol 25mg PO ½ dose Fibrinolytic

9. Total STEMI N=2,262 PCI Hosp N=496 Zone 1 Hosp N=1,031 Zone 2 Hosp N=735 PPCI N=496 PPCI N=1,005 Ph-Inv N=26 Ph-Inv N=580 PPCI N=155 PPCI N=1,501 Ph-Inv N=606

10. Baseline characteristicsPPCIPh-Inv P value Age 62.1 ± 14.763.3 ± 13.60.083 Patients ≥ 75 394 (23.8)147 (24.3)0.82 Male 1176 (71.0)446 (73.6)0.23 Hyperlipidemia 861 (54.0)314 (54.0)0.99 Hypertension 945 (57.6)332 (54.9)0.26 Diabetes 250 (15.2)99 (16.4)0.50 Current Smoking 620 (37.8)247 (41.0)0.17 History of MI 315 (19.1)114 (18.8)0.88 History of CABG 115 (7.0)34 (5.6)0.25 History of PCI 333 (20.2)111 (18.3)0.32

11. Clinical characteristicsPPCIPh-Inv P value Cardiogenic shock before PCI 166 (10.0)47 (7.8)0.10 Cardiac arrest before PCI 154 (9.3)42 (6.9)0.076 Out of hosp cardiac arrest 96 (5.8)23 (3.8)0.059 Anterior MI 558 (34.4)211 (35.3)0.71 Killip Class 2-4 233 (14.1)82 (13.5)0.74 LBBB 57 (3.5)14 (2.3)0.16 TIMI Risk score 4.2 ± 2.44.2 ± 2.50.94

12. PCI HospPPCI N=496 Zone 1 (<60)PPCI N=1,005 Zone 2 (60-210)Ph-Inv N=606 P value PCI Hosp vs. Zone 2 D2B time64 (44,84)95 (81,117)123 (102,151)<0.0001 Mortality hospital 5.0%4.4%5.5%0.76 Mortality 30 day 5.7%5.2%5.8%0.93 Reischemia 30 days 3.0%0.9%1.0%0.014 Major Bleeding 1.4%0.7%1.2%0.71 Stroke 30 days 1.2%0.5%1.0%0.73 Results

13. ICH in Pharmaco-invasive patients 3 Intracranial hemorrhage (0.5%)  74 yr old male – survived  82 yr old female – survived  57 yr old male – survived

14. Kaplan-Meier Survival PPCI Ph-Inv

15. Pre-PCI Patency P<0.001 PPCI Ph-Inv

16. Summary Pharmacologic Regimen: ½ dose Fibrinolytic, Clopidogrel 600mg, UFH, ASA combined with transfer for immediate PCI All patients included unless contraindication to fibrinolytic  Cardiogenic shock – 8%  Elderly – 24% ≥ 75yrs Timing: Median D2B time – 123 minutes Safety: No differences in major bleeding or stroke Efficacy:  Increased pre-PCI patency  Mortality similar to non-transfer PPCI patients  Reduced re-ischemia compared to non-transfer PPCI patients

17. A pharmaco-invasive approach utilizing a reduced dose fibrinolytic combined with immediate transfer for PCI is a safe and effective reperfusion strategy for STEMI patients with expected delays due to long distances to a PCI center Conclusion

18. Thank you