1. Anterior Depressions Angiographic and Clinical Outcomes Among Patients with Acute Coronary Syndromes Presenting with Anterior ST-Segment Depressions C. Michael Gibson, Yuri B. Pride, Satishkumar Mohanavelu, Stephen D. Wiviott, Elliott M. Antman and Eugene Braunwald AHA Scientific Sessions 2008 New Orleans Disclosure Statement: TRITON-TIMI 38 was supported by a research grant to the Brigham and Women’s Hospital from Daiichi Sankyo and Eli Lilly. None of the individual authors has any relevant conflicts to report.

2. Anterior Depressions BACKGROUND Rapid triage of patients with an acute coronary syndrome (ACS) to an appropriate pharmacologic and / or invasive strategy is associated with improved outcomesRapid triage of patients with an acute coronary syndrome (ACS) to an appropriate pharmacologic and / or invasive strategy is associated with improved outcomes The traditional 12-lead electrocardiogram (ECG) is one diagnostic modality in the initial evaluation of patients with chest painThe traditional 12-lead electrocardiogram (ECG) is one diagnostic modality in the initial evaluation of patients with chest pain The presence of ST-segment elevation is the key branch point in the triage to emergent reperfusion therapyThe presence of ST-segment elevation is the key branch point in the triage to emergent reperfusion therapy

3. Anterior Depressions BACKGROUND Anterior ST-segment depressions Unstable angina or non-ST-segment elevation myocardial infarction Risk stratification Conservative or early invasive strategy Acute thrombotic occlusion in the posterior circulation Antiplatelet and antithrombotic therapy EMERGENT REPERFUSION THERAPY

4. Anterior Depressions GOALS To determine the angiographic and clinical outcomes among patients presenting with ACS and isolated anterior ST-segment depression on 12-lead ECG To compare the clinician diagnosis of STEMI with subsequent angiographic evidence, such as an occluded culprit artery, and serologic evidence of myocardial necrosis To determine the diagnostic ECG-to-PCI time among patients with an occluded culprit artery

5. Anterior Depressions MAIN TRIAL DESIGN Double-blind ACS (STEMI or UA/NSTEMI) & Planned PCI PRASUGREL 60 mg LD/ 10 mg MD CLOPIDOGREL 300 mg LD/ 75 mg MD 1 o endpoint: CV death, MI, Stroke Duration of therapy: 6-15 months n=13,608 Diagnostic ECG Angiography / PCI

6. Anterior Depressions METHODS Patients with isolated anterior ST-segment depression were included in the analysis  Patients with ST-segment elevation in other arterial territories were excluded ECGs and angiograms were evaluated by local investigators

7. Anterior Depressions METHODS Anterior ST-segment depressions Unstable angina TFG 2/3 in culprit artery NSTEMI - Tn + Tn “STEMI” + Tn TFG 0/1 in culprit artery

8. Anterior Depressions METHODS Outcomes  Composite of death or MI at 30 days  Fold elevation in cardiac biomarkers As a surrogate for infarct size  Recognition of STEMI by local investigators  Time from diagnostic ECG to PCI

9. Anterior Depressions POPULATION 1,198 patients with isolated anterior depressions 13,608 patients enrolled in TRITON-TIMI 38 243 with UA (20.2%) 641 with NSTEMI (53.5%) 314 with “STEMI” (26.2%) TFG 2/3 - Tn TFG 2/3 + Tn TFG 0/1 + Tn

10. Anterior Depressions BASELINE CHARACTERISTICS Characteristic“STEMI”(n=314)UA/NSTEMI(n=884)p-value Male71%65%0.054 Age, yrs (mean)62630.35 Diabetes19%22%0.15 Hypertension60%71%<0.05 Hyperlipidemia50%54%0.072 Prior MI15%17%0.55 Smoker33%30%0.38 BMI, kg/m 2 (mean)28280.86 CrCl, ml/min (mean)101990.45

11. Anterior Depressions CULPRIT ARTERY IN “STEMI”* PATIENTS n=106n=56n=152 * TFG 0/1 in culprit artery Positive cardiac biomarkers

12. Anterior Depressions 3-way p=0.006 CLINICAL OUTCOMES 30-day death or MI n=641n=314 n=243 TFG 2/3 - Tn TFG 2/3 + Tn TFG 0/1 + Tn

13. Anterior Depressions INFARCT SIZE p<0.001 n=884 n=314

14. Anterior Depressions INFARCT SIZE BY CULPRIT ARTERY p<0.05 for all

15. Anterior Depressions MANAGEMENT Among patients with an occluded culprit artery and anterior ST-segment depression, only 14/314 (4.5%) were interpreted by the investigator as a STEMI The median time from baseline ECG to PCI for patients with an occluded culprit artery was 29.4 hours (IQR 26.1-44.1 hours) None of the patients with an occluded artery had an ECG to PCI time <6 hours

16. Anterior Depressions LIMITATIONS Only patients who survived until angiography were included  Due to survival bias, this dataset may therefore underestimate the number of patients with anterior ST-segment depression who have an occluded artery ECGs were read locally, not by a core laboratory, and so subtle ST-segment elevation cannot be excluded

17. Anterior Depressions CONCLUSIONS More than a quarter of patients with ACS who present with isolated anterior ST- segment depressions in TRITON-TIMI 38 had an occluded culprit artery and positive cardiac biomarkers The occluded artery was most often the left circumflex artery

18. Anterior Depressions CONCLUSIONS Patients with anterior ST-segment depression and an occluded culprit artery had significantly larger infarcts and worse short-term clinical outcomes These ECG findings frequently went unrecognized as evidence of a possibly occluded culprit artery This suggests the need for improved methods to identify patients with isolated anterior ST-segment depression who have an occluded artery