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

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

Reperfusion Options for Patients with Expected Delays1) 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

Current Guidelines for STEMI Patients With

Expected Delays to PCI

Fibrinolysis Recommended if:

ACC/AHA ESC

First Medical Contact (Door) to balloon

> 90 minutes > 120 minutes

Unresolved Issues

• Timing of PCI following fibrinolysis

• Optimal pharmacologic regimen

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

• 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

PPCI

Ph-Inv

Primary PCI protocol (Zone 1 < 60 miles)

Aspirin 324mgClopidogrel 600mgUFH 60/kg load, 12/kg/hr infusionMetoprolol 25mg PO

Ph-Inv PCI protocol (Zone 2: 60-210 miles)

Aspirin 324mg POClopidogrel 600mg POUFH 60/kg load, 12/kg/hr infusionMetoprolol 25mg PO½ dose Fibrinolytic

Total STEMIN=2,262

PCI HospN=496

Zone 1 HospN=1,031

Zone 2 HospN=735

PPCIN=496

PPCIN=1,005

Ph-InvN=26

Ph-InvN=580

PPCIN=155

PPCIN=1,501

Ph-InvN=606

Baseline characteristicsPPCI PPCI Ph-InvPh-Inv P value

Age62.1 ± 14.7 63.3 ± 13.6 0.083

Patients ≥ 75394 (23.8) 147 (24.3) 0.82

Male1176 (71.0) 446 (73.6) 0.23

Hyperlipidemia861 (54.0) 314 (54.0) 0.99

Hypertension945 (57.6) 332 (54.9) 0.26

Diabetes250 (15.2) 99 (16.4) 0.50

Current Smoking620 (37.8) 247 (41.0) 0.17

History of MI315 (19.1) 114 (18.8) 0.88

History of CABG115 (7.0) 34 (5.6) 0.25

History of PCI333 (20.2) 111 (18.3) 0.32

Clinical characteristicsPPCIPPCI Ph-InvPh-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 MI558 (34.4) 211 (35.3) 0.71

Killip Class 2-4233 (14.1) 82 (13.5) 0.74

LBBB57 (3.5) 14 (2.3) 0.16

TIMI Risk score4.2 ± 2.4 4.2 ± 2.5 0.94

PCI HospPPCIPPCIN=496

Zone 1 (<60)PPCIPPCIN=1,005

Zone 2 (60-210)Ph-InvPh-InvN=606

P valuePCI Hosp vs. Zone 2

D2B time 64 (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

Reischemia30 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

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

Kaplan-Meier Survival

0.00

0.25

0.50

0.75

1.00

Su

rviv

al p

rob

ab

ility

0 100 200 300 400Days since presentation

PPCI

PI

One-Year Survival

PPCIPh-Inv

Pre-PCI Patency

47.1

72.7

0

10

20

30

40

50

60

70

80

TIMI 2/3

Per

cent

age

of p

atie

nts

P<0.001

PPCI

Ph-Inv

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

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

Thank you