1. Patient Transfer Mark de Belder The James Cook University Hospital Middlesbrough

2. Current Management Strategies for ACS ACS No ST Elevation Early Conservative Early Invasive Fibrinolysis ST Elevation Primary PCI Fibrinolysis ST Elevation Primary PCI Fibrinolysis ST Elevation PRIMARY PCI

3. Guidelines for the management of non-STEMI Acute Coronary Syndromes Coping with ACS angiography Rapid turnover of patients required (pressure on ambulance services) Organisation of diagnostic and revascularisation services Cath lab spaces required every day in interventional centres Referral to a specific cath lab slot rather than a specific Consultant Increased use of Cath ? Proceed slots (for elective work as well) Referring hospitals need to take some patients back after revascularisation (?swaps) Weekend working? Elective work may have to slow pending an increase in the infrastructure for angiography Clinical networks with appropriate support from commissioners

4. Patient Transfer in the setting of STEMI

5. Meta-analysis of 23 randomised trials Meta-analysis of 23 randomised trials 7739 patients: 4-6 week data Keeley EC, Boura JA, Grines CL The Lancet 2003;361:13-20 P=0.0002P=0.0003P<0.0001P=0.0004P<0.0001

6. Meta-analysis of 8 randomised trials Streptokinase trials - 1837 patients Meta-analysis of 8 randomised trials Streptokinase trials - 1837 patients Keeley EC, Boura JA, Grines CL The Lancet 2003;361:13-20 0.53 (0.37-0.75)0.11 (0.05-0.26)0.32 (0.09-1.21)0.40 (0.28-0.58)

7. Meta-analysis of 15 randomised trials Fibrin-specific trials - 5902 patients Meta-analysis of 15 randomised trials Fibrin-specific trials - 5902 patients Keeley EC, Boura JA, Grines CL The Lancet 2003;361:13-20 0.80 (0.66-0.96)0.42 (0.31-0.550.49 (0.31-0.77)0.57 (0.48-0.69)

8. Meta-analysis of 5 randomised trials Transfer for PCI vs On-Site Lysis 2909 patients: 4-6 week data Meta-analysis of 5 randomised trials Transfer for PCI vs On-Site Lysis 2909 patients: 4-6 week data Keeley EC, Boura JA, Grines CL The Lancet 2003;361:13-20 P=0.057P<0.0001P=0.049P<0.0001

9. Mortality by time to presentation Ziljstra EHJ 2002;23:556

10. 30-day mortality by time from enrollment to first balloon inflation Berger P et al, Circ 1999;100:14-20 (GUSTO-IIb)

11. Door-to-Balloon times in Primary PCI outside of trials N=27,080 Door-to-Balloon times in Primary PCI outside of trials N=27,080 Cannon CP, Gibson CM, et al. JAMA 2000 P=NS P=0.01P=0.0007P=0.0003 N=2,230N=5734N=6616N=4461N=2627N=5412 Corrected for age, anterior MI location & gender

12. CAPTIM Comparison of Angioplasty and Prehospital Thrombolysis in Acute Myocardial Infarction Bonnefoy E et al, The Lancet 2002;360:825-29 A trial of prehospital fibrinolysis plus selected PCI

13. CAPTIM Comparison of Angioplasty and Prehospital Thrombolysis in Acute Myocardial Infarction Bonnefoy E et al, The Lancet 2002;360:825-29 Pre-hospital lysis n=419 Primary PCI n=421 P value 30 day Composite 34 (8.2%)26 (6.2%)0.29 Death16 (3.8%)20 (4.8%)0.61 Reinfarction15 (3.7%)7 (1.7%)0.13 Death & recurrent ischaemia 57 (13.5%)41 (9.8%)0.06 Disabling Stroke4 (1%)00.12 Physician-manned mobile emergency-care units (Service d’Aide Medicale d’Urgence – SAMU) Planned for 1200 patients Trial terminated early due to lack of funding

14. Pre-hospital lysis - ER-TIMI19 Morrow DA et al, JACC 2002;40:71-7 Pre-hospital lysis - ER-TIMI19 Morrow DA et al, JACC 2002;40:71-7 315 pts (65 cath’d) vs 650 in-hospital lysis pts 0306090120150mins 0306090120150 mins EMS Arrival EMS Arrival Pre-hosp rPA In-hospital lysis ED Arrival 13% >70% STres 90mins post-lysis 49% >70% STres 33% >70% STres 90mins post-lysis 48% >70% STres 4.7% death 3.3% reMI 1% ICH 65 (21%) cath’d 56 (18%) PCI

15. Why so little primary PCI in UK? Lack of evidence? Belief in pre-hospital lysis? Insufficient PCI centres? Too few cardiologists? (Interventional) cardiologists have too many other things to do? Reluctance to take on nocturnal work? Competing demands for finances (statins, ACE-I, DES, ICDs etc)? Lack of organisation?

16. Transferring patients for Primary PCI Zijlstra F et al, Heart 1997;78:333-6 The Weezenlanden Hospital, Zwolle Local patients N=416 Transferred N=104 Symptom-onset to admission 129 (69) mins90 (60) mins Local admission to WZL admission -70 (27) mins WZL door-to-balloon time 67 (28) mins39 (31) mins Total ischaemia time196 (74) mins200 (62) mins 10 in shock (1 died) 1 ventilated prior to transfer 1 intubated during transfer 1 VT – lignocaine 2 VF – defibrillated 2 required IV fluids Transfer patients (104)

17. Helicopter vs Ambulance transfer for Primary PCI Straumann E et al, Heart 1999;82:415-9 Triemli Hospital, Zurich Ambulance N=54 Helicopter N=14 Total N=68 Sig Distance (km) 8 (5-68)42 (24-122)9 (5-122)0.0001 Journey time (mins) 47 (15-126)37 (7-60) Total transfer time (mins) 50 (18-110)63 (40-115)55 (18-115)0.02 3 patients died in shock prior to transfer 0 patients transferred died 8 patients were ventilated during transfer 0 defibrillation during transfer (15 resuscitated prior to transfer)

18. AIR PAMI 138 patients: 30 day data (trial stopped for poor recruitment) AIR PAMI 138 patients: 30 day data (trial stopped for poor recruitment) Grines CL et al, JACC 2002;39:1713-9 P=0.46P=1.0P=0.11P=0.33P=0.007 79% ambulance transfer 26±28 miles; 21% Helicopter 57±50 miles 0 patients needed resuscitation during transfer, 0 patients died ER to treatment times 174±80 for transfer vs 63±39 mins for local lysis

19. DANAMI-2 22 referring hospitals 5 PCI centres Serving two thirds of the Danish population (5.4million) Plan for 1100 patients at referring hospitals and 800 patients at invasive centres Average distance 35 miles (56km) Up to 95 miles (153km) Halted by Safety & Efficacy Committee after 1129 patients enrolled because of clear efficacy in PCI patients

20. DANAMI-2 Trial design Primary Endpoint: Death, Reinfarction, or Disabling Stroke through 30 days ST-elevation MI < 12 hours Randomization (total planned 1900 pts) * Referral Hospital: Planned 1100 pts at 24 sites * Angioplasty Center: Planned 800 pts at 5 sites Fibrinolysis Accelerated tPA (max. 100 mg) Stent Acute transfer for 1° PTCA + stent Anderson HR et al, ACC 2002; Oral Presentation

21. DANAMI-2 - Time from Symptom Onset to Admission and Time from Door to Rx Door to t-PA Door to PCI (Balloon) transfer admit to transfer Symptom to Hosp. Door to PCI 0 60 120 180 240 minutes Referral Invasive Referral Invasive Lysis 1° PCI Hospital Average Door to Balloon (jncludestransfer) < 120 minutes Door to t-PA Symptom to Hosp. ACC 2002; Oral presentation

22. DANAMI-2 Transfer problems AF in 2.5% VT in 0.2% VF 1.4% 2/3 heart block in 2.3% 0 intubations 0 deaths

23. DANAMI-2: 30 day Primary Endpoint 13.7 7.6 6.3 2.0 6.6 1.6 1.1 8.0 0 5 10 15 20 p = 0.0003 p = 0.35 p < 0.001 p = 0.15 Accel. t-PA (n=782)PCI (n=790) Combined*DeathReinfarctionDisabling Stroke *Primary Endpoint: Death, Reinfarction, or Stroke % of Patients All Patients ACC 2002; Oral presentation

24. DANAMI-2: 30 day Primary Endpoint* 13.7 14.2 12.3 8.5 6.7 8.0 0 5 10 15 20 p=0.0003 p=0.002 p=0.048 Accel. t-PAPCI All patients (n=1572) Referral hospitals (n=1129) Invasive Centers (n=443) *Primary Endpoint: Death or Reinfarction or Stroke % of Patients Referral vs. Invasive Hospitals ACC 2002; Oral presentation

25. DANAMI 2: Time to treatment 30 day results Combined end-point - All significant

26. DANAMI 2: Results by age group 30 day results Combined end-point - All significant

27. PRAGUE 2 Widimsky P et al, ESC 2002

28. PRAGUE 2: 30 day mortality P<0.02 P=0.12P=NS Widimsky P et al, ESC 2002 Trial stopped early because of reluctance to enrol patients >3 hours

29. Shock patients Hochman JS et al, NEJM 1999;341:625-34

30. Ambulance transfer

31. Strategy for centres with door-to-balloon times >120 mins? Send anyway for primary PCI? Make do with best lysis strategy? As above and select out patients for rescue? Conventional lysis and send for rescue on arrival if required? Half-dose lysis ± GP IIb/IIIa inhibitor and send?

32. Facilitated PCI Studies such as PACT, SPEED, TIMI-14 and GUSTO V suggest that –combination pharmacotherapy may improve effects of fibrinolysis, and –pharmacotherapy combined with a PCI strategy may improve results of PCI FINESSE and ASSENT IV ongoing High risk patients who cannot be treated with early PCI

33. Current Process for Infarct Angioplasty MI Ambulance Centre

34. MI Centres MI Ambulance Centre

35. DANAMI-2 - Time from Symptom Onset to Admission and Time from Door to Rx Potential impact of MI centres Door to t-PA Door to PCI (Balloon) transfer Symptom to Hosp. Door to PCI 0 60 120 180 240 minutes Referral Invasive Referral Invasive Lysis 1° PCI Hospital Could reduce time by 50-60 mins Door to t-PA Symptom to Hosp. Paradox: referral patients might get more rapid reperfusion!

36. MI Centres MI Ambulance Centre MI Ambulance Centre As per C-PORT

37. Emergency Ambulance Service Hartlepool3 Stockton 3 Carlton How1 Redcar3 Middlesbrough3 Coulby Newham1/2 Blue light trained 1

38. Government policy Get the best out of the old treatments before looking at new ones Pilot studies of pre-hospital lysis –But data already available from Scotland, N. Ireland, France, Holland, Germany, Belgium, USA and Israel! Is there one? Get the best out of the old treatments and look at new ones Look at studies of pre-hospital lysis and allow (ie fund) introduction (?via NICE) Look at studies of primary PCI and allow (ie fund) introduction (?via NICE) A better approach?

39. Conclusions If clinical investigators can organise trials, then governments, commissioners and clinical cardiologists should be able to organise an infarct angioplasty service

40. Conclusions Patient transfer in AMI Feasible Cardiovascular events are uncommon Need paramedics, ALS trained nurses or doctors Appropriately equipped ambulances –Continuous ECG monitoring –Defibrillation –Mechanical ventilation –Thrombolytic agents –IV fluids –Resuscitation drugs –Ability to transfer IABP Need new law to oblige rapid ambulance response to AMI transfer requests (<8 minute response time)

41. Conclusions Primary PCI vs Fibrinolysis If hospital fibrinolysis is local strategy, change to primary PCI, at least for all patients presenting >3 (?>2) hours after symptom onset If pre-hospital fibrinolysis is local strategy, need appropriate numbers of appropriately equipped and staffed ambulances Such a strategy requires a PCI strategy –Contraindication to lysis –Early shock –High risk rescues –Re-infarction If such ambulance crews exist, then use them for transfer for primary PCI (as the PCI team exists anyway)!

42. Conclusions For PCI centres (on-site surgery) with 4 or more interventionists – –primary PCI should be preferred treatment for STEMI –??offer fibrin-specific lysis to patients presenting in first 3 hours at night) For PCI centres with off-site surgery - Local arrangements needed for surgical candidates.

43. Conclusions For centres that cannot offer PCI but transfer possible within 3 hours - –transfer patients to local PCI centre for primary PCI –??offer fibrin-specific lysis to patients presenting in first 3 hours – but respond to ongoing problems). For centres that cannot offer PCI, when transfer within 3 hours not possible - –use fibrinolysis but consider protocol for immediate transfer of patients to PCI centre (?all-comers or selective). Role of facilitated PCI to be determined

45. DANAMI 2: 30 day results P<0.0001

46. DANAMI-2 600 day data (6months-4 years) 300.111.9%15.3%Mortality - Referral hospitals 400.2613.4%16%Mortality - All patients 150.00416.9%23.3%Combined - Referral hospitals 180.00217.8%24.2%Combined - All patients NNTP valuePCIFibrinolysisEnd-point Anderson HR et al, XIVth World Congress of Cardiology 2002

47. Is simple primary PCI still going to be best? Vermeer et al, Heart 1999;82:426-31