Anterior Depressions Angiographic and Clinical Outcomes Among Patients

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.

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 outcomes • The 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 therapy

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

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

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

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

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

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

POPULATION Anterior Depressions 13, 608 patients enrolled in TRITON-TIMI 38 1, 198 patients with isolated anterior depressions 243 with UA (20. 2%) TFG 2/3 - Tn 641 with NSTEMI (53. 5%) TFG 2/3 + Tn 314 with “STEMI” (26. 2%) TFG 0/1 + Tn

BASELINE CHARACTERISTICS Anterior Depressions Characteristic Male “STEMI” (n=314) UA/NSTEMI (n=884) p-value 71% 65% 0. 054 62 63 0. 35 Diabetes 19% 22% 0. 15 Hypertension 60% 71% <0. 05 Hyperlipidemia 50% 54% 0. 072 Prior MI 15% 17% 0. 55 Smoker 33% 30% 0. 38 BMI, kg/m 2 (mean) 28 28 0. 86 Cr. Cl, ml/min (mean) 101 99 0. 45 Age, yrs (mean)

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

Anterior Depressions CLINICAL OUTCOMES 30 -day death or MI 3 -way p=0. 006 n=243 n=641 n=314 TFG 2/3 - Tn TFG 2/3 + Tn TFG 0/1 + Tn

INFARCT SIZE Anterior Depressions p<0. 001 n=884 n=314

Anterior Depressions INFARCT SIZE BY CULPRIT ARTERY p<0. 05 for all

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

Anterior Depressions LIMITATIONS • Only patients who survived until angiography were included ØDue 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

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

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