1. Prehospital Fibrinolysis with Double Antiplatelet Therapy in Acute ST-Elevation Myocardial Infarction: The Clarity Ambulance Substudy Prehospital Fibrinolysis with Double Antiplatelet Therapy in Acute ST-Elevation Myocardial Infarction: The Clarity Ambulance Substudy

2. Montalescot G. ESC, September 2005 Ambulance Substudy Background Fibrinolysis for ST-elevation acute myocardial infarction (STEMI) is frequently limited by delays of administration as well as incomplete reperfusion or reocclusion of the infarct-related artery 1 Intensified prehospital management may shorten time to treatment and improve outcomes 2 1. Brouwer MA et al. Circulation 2002; 106: 659–665. 2. Morrison LJ et al. JAMA 2000; 283: 2686–2692.

3. Montalescot G. ESC, September 2005 Substudy Sites and Patient Numbers France: 172 patients L Soulat: 57 Y Lambert: 48 F Lapostolle: 28 F Thieuleux: 21 C Gully: 10 D Pollet: 5 D Galley: 2 L Olliver: 1 UK: 40 patients J Adgey: 27 J Purvis: 13 Sweden: 5 patients J-E Karlsson: 5 217 patients in total

4. Montalescot G. ESC, September 2005 Baseline Characteristics: Ambulance vs. Non-Ambulance Characteristic Ambulance (n=216) Non-ambulance (n=3275) Age (years, mean  SD)57  1158  10 Male (%)8180 Hypertension (%)35 Dyslipidaemia (%)3632 Current smoker (%)4950 Diabetes (%)1317 Prior MI (%)109 Anterior MI (%)41 Fibrin-specific lytic (%)10067 Betablockers (%)8689

5. Montalescot G. ESC, September 2005 Patient management Ambulance (n=216) Non-ambulance (n=3275) Symptom onset to randomization (hours) 1.92.8 * Symptom onset to fibrinolytic (hours) 1.92.8 * Total duration of ischaemic symptoms (hours, mean  SD ) 3.7  2.4 5.1  5.3 * Fibrinolytic to study drug (min) 10 Time to angiography (hours) 6887 Patient Management: Ambulance vs. Non-Ambulance *p <0.001 versus ambulance patients; values are median unless otherwise specified

6. Montalescot G. ESC, September 2005 Angiographic & ECG Parameters: Ambulance vs. Non-Ambulance TFG 364.4 NS Complete* ST resolution at ECG 90 min 180 min 47.2 63.2 37.0 52.7 0.02 0.05 *Complete considered to be >70%; ECG=electrocardiogram p value Event rate (%) AmbulanceNon- ambulance Non-ambulance better Ambulance better Odds ratio (95% CI) 0.501.01.52.0 2.5 3.0

7. Montalescot G. ESC, September 2005 Primary Outcome Parameters: Ambulance vs. Non-Ambulance Primary efficacy endpoint*21.818.1NS TFG 0/117.114.9NS 30-day clinical outcome Cardiovascular death Re-MI Re-ischaemia urging revascularization Overall 4.6 7.4 2.3 13.4 4.4 4.8 4.1 12.9 NS 0.05 NS p value Event rate (%) AmbulanceNon- ambulance *Occluded infarct artery (TFG 0/1) + death + re-MI prior to angiography; NS=not significant Ambulance better Non-ambulance better Odds ratio (95% CI) 0.501.01.52.0 2.5 3.0

8. Montalescot G. ESC, September 2005 Characteristic Clopidogrel (n=109) Placebo (n=107) Age (years  SD)57  1056  12 Male (%)8081 Hypertension (%)3336 Dyslipidaemia (%)3339 Current smoker (%)5443 Diabetes (%)1215 Prior MI (%)811 Anterior MI (%)3548 Fibrin-specific lytic (%)10099 Betablockers (%)8588 Baseline Characteristics: Ambulance Subgroup

9. Montalescot G. ESC, September 2005 Primary Outcome Parameters: Ambulance Subgroup Primary efficacy endpoint*16.527.10.06 TFG 0/111.822.30.05 30-day clinical outcome Cardiovascular death Re-MI Re-ischaemia urging revascularization Overall 5.5 1.8 12.8 3.7 9.3 2.8 14.0 NS p value Event rate (%) ClopidogrelPlacebo Clopidogrel better Placebo better Odds ratio (95% CI) 0.501.01.52.0 2.5 3.0 *Occluded infarct artery (TFG 0/1) + death + re-MI prior to angiography

10. Montalescot G. ESC, September 2005 00.51.01.52.0 Ambulance Non-ambulance Overall Clopidogrel betterPlacebo better Odds ratio (95% CI) Primary Endpoint of TIMI Flow Grade 0/1, MI or Death 0.60 (0.30  1.17) 0.64 (0.53  0.76) 0.65 (0.54  0.77)

11. Montalescot G. ESC, September 2005 Safety: Bleeding Complications TIMI=thrombolysis in myocardial infarction; ICH=intracranial hemorrhage Bleeding complicationsEvent rates (%)p value AmbulanceNon-ambulance TIMI major bleeding by day after angiography 1.01.2NS ICH1.00.6NS TIMI major bleeding by 30 days3.41.7NS ClopidogrelPlacebo TIMI major bleeding by day after angiography 01.9  ICH01.9  TIMI major bleeding by 30 days1.94.9NS

12. Montalescot G. ESC, September 2005 Conclusions Medical reperfusion of STEMI patients with fibrinolysis, heparin, ASA and clopidogrel is feasible before reaching the hospital in medically equipped ambulances without an apparent increase in bleeding Early management of patients in the ambulance is associated with shorter ischaemic times and faster reperfusion, with a consistent treatment effect in favour of clopidogrel in comparison with the overall results