1. Welcome Ask The Experts March 24-27, 2007 New Orleans, LA

2. Incorporating Patient Risk into Decisions Regarding the Optimal Reperfusion Strategy for ST Elevation MI Incorporating Patient Risk into Decisions Regarding the Optimal Reperfusion Strategy for ST Elevation MI Duane S. Pinto, MD Assistant Professor of Medicine Harvard Medical School Director, Cardiology Fellowship Training Program Beth Israel Deaconess Medical Center Boston, MA

3. Harvard Medical School PAMIPAMI (Grines et al. N Engl J Med 1993;328:673)

4. Harvard Medical School GUSTO IIb  29% (N Engl J Med 1997; 336: 1621)

5. Harvard Medical School PCI Frequency (%) P=0.0002 P=0.0003 P < 0.0001 P=0.0004 P=0.032 Death Death, no SHOCK data ReMI Rec. Ischemia Total Stroke Hem. Stroke Major Bleed Death MI CVA Fibrinolysis N = 7739 Keeley E. et al., Lancet 2003; 361:13-20. PCI vs Fibrinolysis for STEMI: Short Term Clinical Outcomes

6. Harvard Medical School Importance of Rapid Time to Treatment With Fibrinolysis in STEMI Time from onset of symptoms to treatment (hours) Absolute % difference in mortality at 35 days 3.5%  2.5%  1.8%   1.6%  0.5%  0.0 1.0 3.0 2.0 4.0 0 – 12 – 34 – 67 – 1212 – 24 The Fibrinolytics Therapy Trialists’ collaborative group. Lancet. 1994; 343:311.

7. Harvard Medical School NRMI 2: Primary PCI Door-to-Balloon Time vs. Mortality Door-to-Balloon Time (minutes) MV Adjusted Odds of Death P=0.01P=0.0007P=0.0003 n = 2,230 5,734 6,6164,4612,6275,412 Cannon CP, JAMA 2000

8. Harvard Medical School Symptom – balloon inflation (min) One-year mortality, % 6 RCTs of Primary PCI by Zwolle Group 1994 – 2001 N = 1791 RR = 1.08 for each 30 min delay (P = 0.04) P < 0.0001 12 10 8 6 4 2 0 060120180240300360 Symptom Onset-Balloon Time and Mortality in Primary PCI for STEMI DeLuca, Suryapranata, Circ 109:1223, 2004 The relative risk of 1-year mortality increases by 7.5% for each 30-minute delay

9. Harvard Medical School Time from Symptom Onset to Treatment Predicts One-year Mortality with PCI p = 0.006 <2 hrs 2-4 hrs 4-6 hrs p = 0.02 De Luca at al, JACC 2003 >6 hrs All Patients Low-Risk p = NS High-Risk

10. Harvard Medical School PCI-Related Time Delay vs Mortality Benefit in 22 Randomized Studies of PCI vs Fibrinolytic Therapy Nallamothu and Bates, AJC 2003 23 RCTs For every 10 min delay to PCI: 1 % reduction in Mortality Difference Between PCI & Lysis N= 7419 p=0.006

11. Harvard Medical School PCI-Related Time Delay vs Mortality Benefit in 21 Randomized Studies of PCI vs Fibrinolytic Therapy Betriu A, Massotti M. Am J Cardiol. 2005. 100-101 21 RCTs For every 10 min delay to PCI: 0.24 % reduction in Mortality Difference Between PCI & Lysis N= 7350

12. Harvard Medical School PCAT-2 Analysis  Patient level data included in analysis of 22 trials (n=6,763)  PPCI was associated with a  67% reduction in odds of death at 30 days if PCI related delay was <35 minutes  Only 28% if >35 minutes (p=0.004) Boersma E. EHJ. 2006; 27: 779-788.

13. Harvard Medical School Advantage of PCI Compared With Fibrinolysis Decreases as PCI-Related Delay Increases Pinto DS, et al. Circulation. 2006;114:2019-2025. *Betriu A. Am J Cardiol. 2005; 95:100-101. Odds of Death With Fibrinolysis PCI-Related Delay (door-to-balloon–door-to-needle time), min PCI Better Fibrinolysis Better 2.0 1.5 1.25 1.0 0.8 0.5 607590 105 114 135 150165180 Randomized Studies*

14. Harvard Medical School PCI Related Delay (DB-DN) Where PCI and Fibrinolytic Mortality Are Equal (Min) Stratified by Patient Characteristics PCI Related Delay (DB-DN) (Min) 68,716123,793125,73766,77269,331123,178115,29377,141192,509 <120120+ANTNonAnt65+<65 Prehospital Delay (min) Infarct Location Age (years) All Patients Prehospital Delay (min) Infarct Location Age (years) All Patients P<0.05 for all 2 way comparisons Pinto DS, et al. Circulation. 2006;114:2019-2025.

15. Harvard Medical School Meta-analysis of Transfer for PCI vs. Fibrinolysis Dalby M, et al. Circ 2003; 1809 2% beneficial survival rate with PPCI with PCI related time delay of 65 minutes

16. Harvard Medical School Death/MI/Stroke (%) DANAMI-2: Primary Results Lytic Primary PCI P=0.0003 Combined 0 4 12 16 8 14 8 RRR 45% Lytic Primary PCI P=0.002 Transfer Sites 0 4 12 16 8 14 9 RRR 40% Lytic Primary PCI P=0.048 Non-Transfer Sites 0 4 12 16 8 7 12 RRR 45%

17. Harvard Medical School Transportation= 32 min DANAMI-2 Invasive Referral Invasive Referral Minutes Hospitals Fibrinolysis PCI 26 min 060120180240 Door-to-balloon Door-to-needle Door-to- balloon In-door-out-door Prehospital Door-to-needlePrehospital ↑ Randomization-balloon = 90 min Door-balloon = 93 min 45 min 50 min

18. Harvard Medical School Maybe Our Systems Are Not Completely Optimized in the US!

19. Harvard Medical School DANAMI vs US AMI: Are We As Quick in the US? Pinto DS, et al. Cardiovascular Reviews and Report. 2003;24:267-276. 0 Median Time (min) DANAMI On-Site Primary PCI DANAMI On-Site Primary PCI DANAMI Transfer Primary PCI DANAMI Transfer Primary PCI US AMI Transfer Primary PCI US AMI Transfer Primary PCI 90 110 185 50 100 150 200 225 25 75 125 175

20. Harvard Medical School Times in Randomized Trials vs. the “Real World” BK Nallamothu, ER Bates, HM Krumholz, et al. Circulation 2005; 761 Median Door to Balloon Time: 180 min Median Door to Door (Transfer) Time: 120 Min Median PCI Hospital DB time: 53 Min <5% of patients had Total DB time <90 Min if a transfer was involved Compare this to the randomized studies with: Total DB times of 90 min, Transport times of 30 min, and PCI hospital DB times of 25 min

21. Harvard Medical School PCI-Related Time Delay vs Mortality Benefit in 22 Randomized Studies of PCI vs Fibrinolytic Therapy Nallamothu and Bates, AJC 2003 23 RCTs For every 10 min delay to PCI: 1 % reduction in Mortality Difference Between PCI & Lysis N= 7419 p=0.006 DANAMI: on site PCI 90 DB – 50 DN = 40 min delay DANAMI: with transfer 110 DB – 50 DN = 60 min delay “USA AMI” with transfer: 171 DB – 32 DN = 139 min delay DANAMI: on site PCI 90 DB – 50 DN = 40 min delay DANAMI: with transfer 110 DB – 50 DN = 60 min delay “USA AMI” with transfer: 171 DB – 32 DN = 139 min delay

22. Harvard Medical School Prehospital Delay & Timing of Reperfusion Strategy Equivalence PCI Related Delay (DB-DN) Where PCI and Fibrinolytic Mortality Are Equal (Min) Prehospital Delay (min) 19,517 5,296 9,812 41,774 16,119 20,424 10,614 3,739

23. Harvard Medical School Gersh, B. J. et al. JAMA 2005;293:979-986. Hypothetical Construct of the Relationship Among the Duration of Symptoms of Acute MI Before Reperfusion Therapy, Mortality Reduction, and Extent of Myocardial Salvage

24. Harvard Medical School One Size Does Not Fit All!

25. Harvard Medical School SummarySummary Simple rules:  DB<90 min  DB-DN <60 min  DN <30 min  Transfer all for PCI, etc are not enough to determine the optimal reperfusion strategy for all patients in all situations are not enough to determine the optimal reperfusion strategy for all patients in all situations

26. Harvard Medical School SummarySummary  The clinician must integrate:  Prehospital Delay  Anticipated STEMI Risk (age, anterior, inferior, shock)  Anticipated Risk for ICH  Anticipated Transfer time/PCI related delay

27. Harvard Medical School SummarySummary  Fibrinolysis is not unreasonable when  PCI associated with unacceptable delay (Class I)  Short time from symptom onset (<1 hr) (Class I)  Primary PCI is superior to Fibrinolysis in several clinical situations, particularly if:  Competent personnel involved  DB times are <90 Min, PCI related Delay Acceptable  High Risk for Bleeding or Complication from MI  Late Presentation

28. Harvard Medical School SummarySummary  The benefits and limitations of Primary PCI should be considered when developing regionalized transfer and community based PCI systems  Continued work is needed to develop pharmacologic strategies to rapidly, effectively, and safely open closed arteries thereby extending the benefit of PCI to a larger group of patients

29. Question&Answer

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