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EXPERTS WORKSHOP ON EARLY TREATMENT STRATEGIES FOR ACUTE MYOCARDIAL INFARCTION FOR THE MIDDLE EAST COUNTRIES FEBRUARY 26 TH -28 TH 2005 / DUBAI, UAE SPONSORED.

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Presentation on theme: "EXPERTS WORKSHOP ON EARLY TREATMENT STRATEGIES FOR ACUTE MYOCARDIAL INFARCTION FOR THE MIDDLE EAST COUNTRIES FEBRUARY 26 TH -28 TH 2005 / DUBAI, UAE SPONSORED."— Presentation transcript:

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 A rationale for pre-hospital thrombolytic therapy Patrick Goldstein

2 Fire! Your house is on fire...

3 The Fire Spreads Quickly Every second is crucial, the damage is getting worse

4 Transportation!? You are watching the firemen loading the burning stuff...

5 To Extinguish the Fire! Time is muscle and life!

6 Cross-sections of left ventricle after experimental coronary artery occlusion (Reimer KA, et al. Circulation. 1977;56: ). Time is Muscle Duration of occlusion 3 h Area supplied by occluded artery x x x x x x x x x x x x x x x x x x x x XXXX Necrosis Ischemic but viable Non-ischemic 24 h 40 min x x x x x x x x x x x x x x x x x x x x x x

7 Acute MI again? Why? It is serious Its desperately urgent We must act efficiently, in order to significantly reduce mortality before arrival at the hospital The diagnosis is clinical The strategy and the therapeutic management are in constant movement

8 Time is muscle MITI Infarct Size (%) < 70 min min

9 Estimated benefit (lives saved at 35 days) per 1000 patients Time from onset (hours) Mortality Reduction Depends on the Delay Onset of Pain - Thrombolytic Treatment Eric Boersmas meta-analysis (22 trials from 83 to patients) BOERSMA, E. et al Early thrombolytic in acute myocardial treatment infarction : reappraisal of the golden hour - Lancet 1996 ; % Delay1-month benefit 30 to 60 min60 to 80 lives saved for 1000 patients 1 to 3 hours30 to 50 lives saved for 1000 patients

10 Morrisons Meta-analysis OBJECTIVE To realize a meta-analysis of randomized trials exploring mortality in pre-hospital vs in-hospital thrombolysed AMI INCLUDED STUDIES 6 studies (n = 6 434) RESULTS Delay pain to treatment : Pre-hospital thrombolysis = 104 min In-hospital thrombolysis = 162 min (diff = 58 min) (p=0.007) Significant reduction of the in-hospital death rate (all causes) with pre-hospital thrombolysis : (- 17%) (OR 0.83; 95% CI, ). JAMA, May Vol N°

11 Delay pain – treatment French experience GIG3A2A3A3+CAPTIMSTIM SAMU ESTIM IdFESTIM Nord

12 Material and Drugs of the SMUR Diagnostics: ECG Mini laboratory Therapeutics: fibrinolytic heparin anti GP IIb/IIIa aspirin nitroglycerine morphine defibrillator electric syringe oxygen and more Monitoring : Scope Sao2

13 ASSENT-3 Plus (Pre-hospital Treatment) Early treatment (ambulance-car) of AMI patients <6 hrs ASA RANDOMIZATION 1:1 TNK-tPA full dose 0.53 mg/kg bolus Unfractionated heparin 60 IU/kg bolus (max IU) 12 IU/kg/hr infusion (max 1000 IU/ hr) target aPTT sec Patients outcome will be compared with matched pairs extracted from the corresponding arm of the ASSENT-3 main study. The same exploratory endpoints (single and composite) as in the ASSENT-3 main study will be evaluated; the influence of time to treatment will be analyzed. (500) TNK-tPA full dose 0.53 mg/kg bolus Enoxaparin 30 mg i.v. bolus 1 mg/kg s.c. twice a day (500)

14 Hours to treatment (median) 3+ Symptom - callCall - arrivalArrival - Rand. Rand. - first drugFirst drug - ER ENOX UFH ASSENT-3 In-hospital Symptom – TNK TNK 45 min

15 Thrombolysis or PTCA still a debate ?

16 CAPTIM Comparison of Angioplasty and Pre-hospital Thrombolysis In acute Myocardial infarction ESC 2001

17 M I C U - SMUR CAPTIM Design ST segment onset of pain < 6 h All received ASA + Heparin Central randomisation In-hospital Pre-hospital PCI thrombolysis Diagnosis positive in 95%

18 Primary Composite (30 day) all-cause mortality recurrent MI disabling stroke Secondary Cardiovascular death New onset of angina Urgent angioplasty Cardiogenic shock Hemorrhagic stoke Severe hemorrhage CAPTIM - Clinical Endpoints

19 Primary endpoint % Death (%) Reinfarction (%) Disabling stroke (%) CAPTIM - Results primary endpoint Pre-hospital thrombolysis n = 419 Primary PCI n = RR = RR = P Value

20 Cardiovascular death (%) New onset of angina (%) Urgent angioplasty (%) Cardiogenic shock (%) Hemorrhagic stoke (%) Severe hemorrhage (%) CAPTIM - secondary endpoints Pre-hospital thrombolysis n = 419 Primary PCI n = 421 P Value <

21 DANAMI-2 DENMARK 5.4 mill. inhabitants 5 PCI centers 24 referral hospitals 62% of Danish population Transport distance up to 95 US miles (mean 35 miles) 100 US miles

22 DANAMI II ACC PCI centers + 22 referring hospitals distance average = 56 km 1129 patients443 patients referring hospitals PCI centers no transferambulance PCI fibrinolysis transferon site fibrinolysis Very high risk patients: ST > 4 mm

23 Comparaison CAPTIM / DANAMI II Thrombolysis PCI p CAPTIM8.2 % 6.2 % 0.29 DANAMI II combined 13.7 % 8.0 % DANAMI II referring 14.2 %8.5 % DANAMI II invasive 12.3 %6.7 % Combined Death, ReMI and stroke

24 CAPTIM DANAMI II combined PHT PCI thrombolysis PCI Death3.8 % 4.8 %7.6 % 6.6 % Disabling1.0 %0.0 %2.0 % 1.1 % stroke Reinfarction3.7 %1.7 %6.3 %1.6 % Look at the single endpoints: 30 days

25 Preventing Reinfarction : IIb/IIIa Inhibitors, Enoxaparin, or Primary PCI PRAGUE-2 30-day deaths 6.8 v 10.0 %, p = 0.12 * 6-month data in press, Simes AHU 2002 ** Pre-hospital administration p < 0.05 reMI, death (PCAT only) ; stroke (PCAT only) CAPTIM 840 PCI t-PA** DANAMI PCI t-PA C-PORT* 451 PCI t-PA PCAT* PCI lytic Death 4.6% 3.7% 6.6% 7.6% 6.2% 7.1% 6.2% 8.2% ReMI 1.7% 3.7% 1.6% 6.3% 5.3% 10.6% 4.8% 9.8% Stoke 0 1.0% 1.1% 2.0% 2.2% 4.0% 0.7% 1.9%

26 DANAMI-2 vs CAPTIM vs ASSENT-3 Mortality at 30 days % (TNK + ENOX) ESSAI TOTAL DANAMI-2CAPTIMASSENT-3ASSENT3+ PCI TT

27 Pre-Hospital Lysis Primary PCI Death CAPTIM 1-Year Results GW Symposium, AHA 2002 Death Pre-Hospital Lysis Primary PCI Sx < 2 hours Sx > 2 hours P=0.057 P= % 5.7% 0% 5% 5.9% 3.7% 0% 10%

28 Pre-Hospital Lysis Primary PCI P=0.032 Shock Randomization to DC CAPTIM 1 Year Results GW Symposium, AHA 2002 P= Shock Randomization to Adm Pre-Hospital Lysis Primary PCI Sx < 2 hours 1.3% 5.3% 0% 5% 0.0% 3.6% 0%

29 All presented periods are median Beginning of pain 65 min Emergency call at SAMU 19 min PEC SMUR Beginning of thrombolysis 35 min 66 min Arrival at hospital 84 min Puncture According to ATLS: 32 min 120 min 185 min E-MUST Comparable periods

30

31 The Lille Experience 4h55 3h 1h49 1h Thr. pre-hosp. Thr. pre-hosp. + angioplasty Thr. hosp. Thr. hosp.+ angioplasty Angioplasty

32 USIC 2000 French nationwide survey designed as a multicenter, prospective longitudinal study over one month Aim: to assess current practices and clinical outcome in patients admitted to an ICU for AMI in France Organisation : in-hospital outcome one-year follow-up

33 One-month Mortality in Patients with Reperfusion Therapy: USIC 2000 n = % 41 % 12 % Primary PTCAIV lysisLysis + PTCA

34 USIC 2000: One-month Mortality in Patients with Reperfusion Therapy n = % 12% 47% Hosp. lysis no PCI Pre-hosp. lysis no PCI Hosp. lysis + PCI Pre-hosp. lysis + PCI Primary PCI

35 Combined Strategy of reperfusion

36 The Combined Strategies of Reperfusion J.M. Julliard : A matched comparison of the combination of prehospital thrombolysis and stand bye rescue angioplasty with primary angioplasty. Am.J. Cardiol ; patients in Paris city Pre-hospital Thrombolysis Angiography at 80 min TIMI (64%) TIMI 2 12 (7%) TIMI 0 50 (29%) angioplasty TIMI 3 91% TIMI 2 7%

37 Which Delays for This Technique of Combined Reperfusion PHTAdmission= min AdmissionAngiography= min Then 2 h after PHT only 2% of patients are TIMI O or 1

38 Outcome after Combined Reperfusion Therapy for AMI, Combining Pre-hospital Thrombolysis with Immediate PTCA and Stent patients with AMI (Paris Sud Cardiovascular Institute) 148 patients with pre-hospital full-dose thrombolytic therapy 131 patients included (median time = 2 h after onset of pain) C. Loubeyre and all. Eur. Heart J ; 22 :

39 131 patients Angiography 95 min after TT 64 (49%) TIMI 3 54 (84%) PTCA 65 (50%) TIMI PTCA 119 (91%) PTCA 114 stent 120/131 TIMI 3 (92%) 9/131 TIMI 2 2 TIMI 0-1 no emergency surgery From C. Loubeyre

40 Long-term follow-up 2 1 year mortality rate : 6% (8 patients) non-fatal re MI : 2 patients survival + no RI rate = 90% 94 patients (70%) symptom free - no re-hospitalization - no revascularization C. Loubeyre. Eur. Heart J ; 22 :

41 Early PCI versus Guided PCI after Lytics in the Modern Era Death Relative risk, fixed model Bilateral CI, 95% for trials, 95% for MA SIAM III0.44 [0.14;1.37] GRACIA [0.26;1.26] CAPITAL-AMI0.67 [0.11;3.89] Total0.54 [0.29;0.99] Cochran Q het. p=0.91 Rel. Risk , p=0.047 RR CI p

42 RESCUE0.53 [0.16;1.75] REACT0.51 [0.24;1.10] MERLIN1.14 [0.59;2.20] LIMI0.84 [0.27;2.65] Belenkie et al0.19 [0.02;1.47] Total0.73 [0.48;1.11] Cochran Q het. P=0.33 Rescue PCI after Lytics Death 6 weeks Relative risk, fixed model Bilateral CI, 95% for trials, 95% for MA Rel. Risk RR CI p

43 Conclusion Pre-hospital thrombolysis is still the gold standard Very high risk patients MUST have a PCI with a minimum delay Transfer is not an additional risk Pre-hospital thrombolysis + Angioplasty

44 Pre-hospital thrombolysis + immediate angioplasty + stent implantation is safe and effective EP. Mc Fadden. Eur. Heart J ; 22 :


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