1. Which Early ST-Elevation Myocardial Infarction Therapy (WEST) Trial Paul W. Armstrong, WEST Steering Committee Published in The European Heart Journal The WEST Trial

2. www. Clinical trial results.org WEST Trial: Background The goal of the trial was to evaluate whether early (pre-hospital if possible) optimal pharmacologic therapy was non-inferior to primary percutaneous coronary intervention (PCI) among patients with ST elevation MI.The goal of the trial was to evaluate whether early (pre-hospital if possible) optimal pharmacologic therapy was non-inferior to primary percutaneous coronary intervention (PCI) among patients with ST elevation MI. Exclusions include primary PCI available within 1 h of diagnosis, contraindications to fibrinolysis, prior coronary bypass grafting (CABG), or glycoprotein IIb/IIIa inhibitor use within 7 days.Exclusions include primary PCI available within 1 h of diagnosis, contraindications to fibrinolysis, prior coronary bypass grafting (CABG), or glycoprotein IIb/IIIa inhibitor use within 7 days. The goal of the trial was to evaluate whether early (pre-hospital if possible) optimal pharmacologic therapy was non-inferior to primary percutaneous coronary intervention (PCI) among patients with ST elevation MI.The goal of the trial was to evaluate whether early (pre-hospital if possible) optimal pharmacologic therapy was non-inferior to primary percutaneous coronary intervention (PCI) among patients with ST elevation MI. Exclusions include primary PCI available within 1 h of diagnosis, contraindications to fibrinolysis, prior coronary bypass grafting (CABG), or glycoprotein IIb/IIIa inhibitor use within 7 days.Exclusions include primary PCI available within 1 h of diagnosis, contraindications to fibrinolysis, prior coronary bypass grafting (CABG), or glycoprotein IIb/IIIa inhibitor use within 7 days. Eur Heart J (2006) Vol. 27, 1530–1538

3. www. Clinical trial results.org WEST Trial: Study Design  Primary Endpoints: Death, reinfarction, refractory ischemia, congestive heart failure, cardiogenic shock or major ventricular arrhythmia by 30 days, evaluated for non-inferiority of the TNK groups relative to the primary PCI group.  Secondary Endpoint: ST-resolution at 90 and 180 minutes; infarct size  Primary Endpoints: Death, reinfarction, refractory ischemia, congestive heart failure, cardiogenic shock or major ventricular arrhythmia by 30 days, evaluated for non-inferiority of the TNK groups relative to the primary PCI group.  Secondary Endpoint: ST-resolution at 90 and 180 minutes; infarct size Tenecteplase (TNK) and usual care n=100 Tenecteplase (TNK) and usual care n=100 TNK and mandatory invasive study within 24 h and rescue PCI if failed reperfusion n=104 n=104 304 patients with STEMI with symptoms ≥20 minutes and high-risk ECG criteria in whom reperfusion therapy (primary PCI, fibrinolysis or transfer for rescue PCI) was feasible within 3 hours of randomization Randomized. 20% female, median age 58 years, mean follow-up 30 days Concomitant medications include aspirin and subcutaneous enoxaparin (1 mg/kg) 304 patients with STEMI with symptoms ≥20 minutes and high-risk ECG criteria in whom reperfusion therapy (primary PCI, fibrinolysis or transfer for rescue PCI) was feasible within 3 hours of randomization Randomized. 20% female, median age 58 years, mean follow-up 30 days Concomitant medications include aspirin and subcutaneous enoxaparin (1 mg/kg) Primary PCI with 300 mg loading dose of clopidogrel n=100 n=100 Eur Heart J (2006) Vol. 27, 1530–1538

4. www. Clinical trial results.org WEST Trial: Primary Endpoint Death or recurrent MI occurred in 13.0%, 6.7%, and 4.0%, respectively (p=0.021 for TNK alone vs. primary PCI; p=0.378 for TNK+invasive study group vs. primary PCI).Death or recurrent MI occurred in 13.0%, 6.7%, and 4.0%, respectively (p=0.021 for TNK alone vs. primary PCI; p=0.378 for TNK+invasive study group vs. primary PCI). There were no ICH in the trial. Major bleeding occurred in 1.0% of the TNK group, 1.9% of the TNK+Invasive study group, and 1.0% of the primary PCI group.There were no ICH in the trial. Major bleeding occurred in 1.0% of the TNK group, 1.9% of the TNK+Invasive study group, and 1.0% of the primary PCI group. Death or Recurrent MI at 30 days Eur Heart J (2006) Vol. 27, 1530–1538 % patients

5. www. Clinical trial results.org WEST Trial: Primary Endpoint The primary composite endpoint at 30 days occurred in 25% of the TNK group, 24% of the TNK+invasive study group, and 23% of the primary PCI group, meeting the non-inferiority criteria.The primary composite endpoint at 30 days occurred in 25% of the TNK group, 24% of the TNK+invasive study group, and 23% of the primary PCI group, meeting the non-inferiority criteria. Primary Composite Endpoint at 30 days Eur Heart J (2006) Vol. 27, 1530–1538 % patients

6. www. Clinical trial results.org WEST Trial: Secondary Endpoint ST- Resolution at 180 minutes Complete ST resolution (≥70%) at 180 minutes was present in 60.8% of the TNK group, 69.4% of the TNK+invasive study group, and 55.7% of the primary PCI group. Median peak CK levels were 1199, 1590, and 1833, respectively (p=0.045) Median peak CK levels were 1199, 1590, and 1833, respectively (p=0.045) NT-proBNP levels were significantly higher in the primary PCI group compared to the TNK group (p=0.019). NT-proBNP levels were significantly higher in the primary PCI group compared to the TNK group (p=0.019). Eur Heart J (2006) Vol. 27, 1530–1538

7. www. Clinical trial results.org WEST Trial: Summary Among patients with ST elevation MI, early reperfusion therapy with TNK, aspirin and enoxaparin or TNK plus routine invasive strategy was non- inferior to primary PCI for the 30 day composite endpoint of death, MI, refractory ischemia, heart failure, cardiogenic shock or major ventricular arrhythmia in this pilot study.Among patients with ST elevation MI, early reperfusion therapy with TNK, aspirin and enoxaparin or TNK plus routine invasive strategy was non- inferior to primary PCI for the 30 day composite endpoint of death, MI, refractory ischemia, heart failure, cardiogenic shock or major ventricular arrhythmia in this pilot study. In the present trial, STEMI was diagnosed early and treatment was initiated early, with 40% of patients receiving pre-hospital randomization.In the present trial, STEMI was diagnosed early and treatment was initiated early, with 40% of patients receiving pre-hospital randomization. The rapid diagnosis and treatment may explain in part some of the differences between the results of the present trial and other ST elevation MI trials comparing medical management with primary PCI.The rapid diagnosis and treatment may explain in part some of the differences between the results of the present trial and other ST elevation MI trials comparing medical management with primary PCI. Unlike the ASSENT-4 PCI trial, TNK with an invasive strategy was not associated with an in-hospital mortality or stroke hazard, possibly because the time from TNK administration to PCI was longer in the present trial.Unlike the ASSENT-4 PCI trial, TNK with an invasive strategy was not associated with an in-hospital mortality or stroke hazard, possibly because the time from TNK administration to PCI was longer in the present trial. Among patients with ST elevation MI, early reperfusion therapy with TNK, aspirin and enoxaparin or TNK plus routine invasive strategy was non- inferior to primary PCI for the 30 day composite endpoint of death, MI, refractory ischemia, heart failure, cardiogenic shock or major ventricular arrhythmia in this pilot study.Among patients with ST elevation MI, early reperfusion therapy with TNK, aspirin and enoxaparin or TNK plus routine invasive strategy was non- inferior to primary PCI for the 30 day composite endpoint of death, MI, refractory ischemia, heart failure, cardiogenic shock or major ventricular arrhythmia in this pilot study. In the present trial, STEMI was diagnosed early and treatment was initiated early, with 40% of patients receiving pre-hospital randomization.In the present trial, STEMI was diagnosed early and treatment was initiated early, with 40% of patients receiving pre-hospital randomization. The rapid diagnosis and treatment may explain in part some of the differences between the results of the present trial and other ST elevation MI trials comparing medical management with primary PCI.The rapid diagnosis and treatment may explain in part some of the differences between the results of the present trial and other ST elevation MI trials comparing medical management with primary PCI. Unlike the ASSENT-4 PCI trial, TNK with an invasive strategy was not associated with an in-hospital mortality or stroke hazard, possibly because the time from TNK administration to PCI was longer in the present trial.Unlike the ASSENT-4 PCI trial, TNK with an invasive strategy was not associated with an in-hospital mortality or stroke hazard, possibly because the time from TNK administration to PCI was longer in the present trial. Eur Heart J (2006) Vol. 27, 1530–1538