1. EXPERTS WORKSHOP ON EARLY TREATMENT STRATEGIES FOR ACUTE MYOCARDIAL INFARCTION FOR THE MIDDLE EAST COUNTRIES FEBRUARY 26 TH -28 TH 2005 / DUBAI, UAE SPONSORED BY BOEHRINGER INGELHEIM SUNDAY, 27 th FEBRUARY – SESSION 2 Physician managed and non-physician managed pre- hospital thrombolysis (and how to organize it) Hans-Richard Arntz

2. Factors Influencing Prehospital Care Strategy Selected strategy for treatment Diagnosis/ Patients preconditions Patients will Timelines Availability of resources Guidelines Capability of Hospitals CBF KARDIOLOGIE

3. STEMI: Reliable Ways to Prehospital Diagnosis trained physician on board MICU trained EMS personnel on board MICU radio/telephone transmission of ECG to a remote physician (e.g. cardiologist or emergency physician in a hospital) CBF KARDIOLOGIE

4. Prehospital ECG: Data ManagementCBF KARDIOLOGIE Transmission to PC Transmission to Fax Computerized ECG analysis Transmission to PCTransmission to Fax

5. ASSENT 3 Plus Study ECG Interpretation (n = 1639) 60% Physicians on-scene (cardiologists, anaesthesiologists, EPs) 23% ECG transmission hospital-based EP 8% ECG transmission to a dedicated study physician 9% trained EMS personnel or computer-assisted interpretation CBF KARDIOLOGIE Welsh B et al, Europ J Emerg Med. 2004

6. Accuracy of Prehospital Diagnosis of AMICBF KARDIOLOGIE TEAHAT (EP relying on clinical signs only) 57% EMIP (Physicians + computerized ECG) 92% BEPS (Physicians + ECG) 97% Berlin (Cardiologists/Anaesthesiologists + ECG) 97% MITI (Paramedics + ECG transmission to hospital-based EP) 98% Netherlands (Nurses + computerized ECG) 97% Waynesboro PA, USA (Nurses/paramedics + ECG) 81% GUSTO 1 (Cardiologists/internists + ECG) 97% GISSI 1 (Cardiologists/internists + ECG) 94%

7. CBF KARDIOLOGIE Prehospital Trop T Bedside Test in Patients with Severe ACS Needing Morphine Treatment (n = 183) Trop T 28 (15 %) 155 (85 %) Diagnosis of emergency physician (ECG) AMI (STEMI)22 (79 %) 80 (52 %) Suspected AMI (e.g. LBBB) 1 ( 4 %) 36 (23 %) no STEMI 5 (17 %) 39 (25 %) positive negative

8. Absolute Reduction of 35-Day Mortality in Relation to Time Interval Onset of Symptoms - TherapyCBF KARDIOLOGIE Boersma et al, Lancet 1996 036912 0 20 40 60 80 Time delay (hrs) Benefit per 1000 treated pts

9. Role of Delay Between Onset of Symptoms to Balloon Inflation for 1-Year MortalityCBF KARDIOLOGIE Relative increase of mortality: 7.5 % / 30 min. of delay * adjusted for age, sex, diabetes and history of CABG/PCI 1-year mortality (%) 12 10 8 6 4 2 0 60 120 180 240 300 360 deLuca et al, Circulation 2004 (Zwolle, The Netherlands n = 1791)

10. 020406080100 -5 0 5 10 15 Thrombolysis vs PCI: Time Dependency of Superiority of PCICBF KARDIOLOGIE Nallamothu et al, Am J Cardiol 2003 020406080100 -5 0 5 10 15 Absolute risk reduction: Death, Re-MI, Stroke (%) Absolute risk reduction: Death (%) Delay until PCI (min) p=0.006 p=0.016 Line of equivalence PCI better Lytics better Line of equivalence PCI better Lytics better

11. Enrolment of Patients in ASSENT 3 Plus 59% with physician on-scene (960/1639) 41% by EMS units without presence of a physician (679/1639) CBF KARDIOLOGIE Welsh B et al, Europ J Emerg Med. 2004

12. Pre-Hospital Components of Delay in ASSENT 3+CBF KARDIOLOGIE Welsh et al, ESC 2004 120 min. 9 25 10 15 20 10 * * * 25 35 59 Symp. to call Call to amb. Amb. to rand. Rand. to treat. Treat. to hosp. 112 min. Time * No MD in ambulance MD in ambulance Symptom to Treatment * p<0.05

13. Dosing of Tenecteplase in ASSENT 3+CBF KARDIOLOGIE Welsh et al, ESC 2004 correct dose > 105 % < 95 % p<0.05 TNK-tPA 74.8 76.3 18.2 21.6 7 2 0 10 20 30 40 50 60 70 80 90 MDno-MD

14. ACC/AHA Guidelines for the Management of STEMI (July 2004) Early presentation (< 3 hrs) and delay to PCI Contact-to-Balloon >90 min Start Lysis - Balloon infl.> 60 min PCI is not an option: prolonged transport vascular access difficulties no experienced PCI team Skilled team available with surgical back up Contact-to balloon < 90 Start Lysis – Ballooninfl.< 60 min High risk from STEMI Shock Killip Class > 3 Contraindication for thrombolysis Symptoms > 3 hrs Diagnosis of STEMI is in doubt CBF KARDIOLOGIE Circulation 2004 Fibrinolysis generally preferred PCI-Strategy generally preferred Symptom duration < 3 hrs and no delay to invasive strategy, no preference for either strategy

15. Prehospital Thrombolysis within 2 hrs after Symptom OnsetCBF KARDIOLOGIE EMIP GREAT MITI BERLIN GUSTO I:27% of pts treated within 2 hrs after symptom onset 1 hr 10% 12% 30% 42% 2 hrs 43% 61% 80% 62% DANAMI II: Start of lysis in 50% of pts later than 3:20 hrs after symptom onset

16. MICUs and Cath labs in Berlin (3,5 Mio Inhabitants)CBF KARDIOLOGIE MICU 24-hrs/day cath lab

17. Diagnosis/random. to PCI Diagnosis/random. to Lysis Symptom duration to diagnosis/random. Door to door Door to needle DANAMI IIPRAGUE II CAPTIM SAMU CBF Berlin NAW/RTH 224 280 190 130 120 12913018317310810760 Minuten 60 153 t 90 t 97 t 82 t 91 NMRI-3/4 Registry 240 293 t 180 4.2% < 90 CBF KARDIOLOGIE Symptom Duration to Start of Reperfusion Therapy 0 50 100 150 200 250 300 350 169 185 72

18. Conclusions I The large number of pts with STEMI/ACS necessitates specific measures of EMS to improve outcome uniform phone number to activate EMS (e.g. 112 as proposed by Council of EU) specific training of EMS personnel to recognize symptoms establish pre-hospital diagnosis of STEMI by on-scene 12 lead ECG establish networks which include EMS, general hospitals, and intervention centres in order to optimize local strategies for reperfusion therapy CBF KARDIOLOGIE

19. Conclusions II Even if prehospital thrombolysis may be easily established in physician managed EMS it has been shown that in a growing number of countries with non-physician managed EMS (e.g. in Canada, Norway, United Kingdom, The Netherlands, Sweden ….) prehospital thrombolysis can be safely and effectively performed provided that EMS personnel is capable of correct ECG lead placement transmission of the ECG to a remote physician or is assisted by computerized ECG interpretation has immediate radio access to a dedicated physician for ECG interpretation or in case of problems uses a reliable reperfusion check list is capable of establishing an i.v. access CBF KARDIOLOGIE