The Strategic Reperfusion Early After STEMI study Implications for - PowerPoint PPT Presentation

The Strategic Reperfusion Early After STEMI study Implications for clinical practice Robert C. Welsh, MD, FRCPC Associate Professor of Medicine Director, Adult Cardiac Catheterization and Interventional Cardiology Co-Chair, Vital Heart Response Co-director, U of A Chest Pain Program

Disclosures – past 5 years Research funding: ‐ Astra Zeneca, Bayer, Boehringer Ingelheim, Bristol Myers-Squibb, Eli Lilly, Johnson and Johnson, Pfizer, Portola, Regado, Roche, sanofi aventis Consultant/honorarium: ‐ Astra Zeneca, Bayer, Bristol Myers-Squibb, Edwards Lifesciences, Eli Lilly, Medtronic, Roche, sanofi-aventis

Reperfusion Therapy

Reperfusion Therapy Experiments in animal models -Ischemic necrosis begins in the subendocardium within 20 minutes of coronary occlusion -Reperfusion achieved within the first hour salvages nearly two-thirds of the myocardium at risk thereafter abrupt declining such that little or no salvage is evident after three to six hours of ischemia. Reimer KA, Lowe JE, Rasmussen MM, et al. The wavefront phenomenon of ischemic cell death. 1. Myocardial infarct size vs duration of coronary occlusion in dogs. Circulation 1977 ; 56:786 – 794.

Primary PCI is the dominant reperfusion strategy but... 1. Regional STEMI programs have diminished reperfusion treatment delay but timely primary PCI remains improbable for many – Primary PCI is a complex, multi-disciplinary and time-sensitive intervention only available in a minority of hospitals ( one out of five U.S. hospitals have primary PCI capacity) 2. The acceptable delay for withholding pharmacological reperfusion in anticipation of PCI is not static and is dependent upon individual patient and temporal characteristics – In patients with high-risk clinical presentation and/or characteristics that predict complications of pharmacological reperfusion; a longer delay to mechanical reperfusion is justified – In early presenting patients (<3 hours) the acceptable delay is abbreviated

Primary Percutaneous Coronary Intervention Door-to-Balloon Time and Mortality in Patients Hospitalized with ST-Elevation Myocardial Infarction: Is 90 Minutes Fast Enough? 30 day mortality Time 30-d Mortality 1-Year Mortality (min) Adjusted Adjusted N=1932 30 7.3 (6.1 – 8.6) 8.8 (7.0 – 10.7) 60 8.8 (7.8 – 9.9) 12.9 (11.6 – 14.2) 90 10.7 (9.8 – 11.6) 16.6 (15.6 – 17.6) 1 year mortality 120 12.8 (12.0 – 13.5) 19.9 (19.1 – 20.8) 150 15.0 (14.3 – 15.7) 22.9 (22.0 – 23.7) 180 17.2 (16.4 – 18.0) 25.5 (24.5 – 26.5) 210 19.4 (18.3 – 20.4) 27.7 (26.5 – 28.9) N=1932 240 21.4 (20.1 – 22.6) 29.5 (28.1 – 30.9) 270 23.2 (21.7 – 24.6) 30.9 (29.4 – 32.5) Rathore SS, et al, Am J Cardiol. 2009 Nov 1;104(9):1198-203

W hich E arly S T Elevation Myocardial Infarction T herapy?

Primary 30-day Composite 30-day Death, Re-MI, Refractory Ischemia, CHF, Cardiogenic Shock or Major ventricular arrhythmia 30 A 25.0% Primary efficacy endpoint (%) 25 B 24.0% C 23.0% 20 15 10 5 0 0 5 10 15 20 25 30 Days Armstrong PW. Eur Heart J. 2006 Jul;27(13):1530-8

Death & Re-MI 30-days 30 25 30-day Death / MI (%) 20 p=0.02 log rank A vs C 15 A 13.0% 10 B 6.7% 5 C 4.0% 0 0 5 10 15 20 25 30 Days Armstrong PW. Eur Heart J. 2006 Jul;27(13):1530-8

A pooled analysis of an early fibrinolytic strategy versus expediated primary PCI from CAPTIM and WEST Sx to Rand’n<2h Sx to Rand’n≥2h Sx to Rand’n<2h Sx to Rand’n≥2h n=364 n=275 n=289 n=234 Westerhout et al, Am Heart J. 2011 Feb;161(2):283-90

A pooled analysis of an early fibrinolytic strategy versus primary PCI from CAPTIM and WEST One year survival by time to treatment p=0.021 FL<2h versus PCI<2h Westerhout et al, Am Heart J. 2011 Feb;161(2):283-90

STREAM STRATEGIC REPERFUSION EARLY AFTER MYOCARDIAL INFARCTION F. Van de Werf, ACC 2013

F. Van de Werf, ACC 2013

STUDY AIM A strategy of early fibrinolysis followed by coronary angiography within 6-24 hours or rescue PCI if needed was compared with standard primary PCI in STEMI patients with at least 2 mm ST-elevation in 2 contiguous leads presenting within 3 hours of symptom onset and unable to undergo primary PCI within 1 hour. F. Van de Werf, ACC 2013 Armstrong PW et al. NEJM, 2013

STUDY PROTOCOL STEMI <3 hrs from onset symptoms, PPCI <60 min not possible, 2 mm ST-elevation in 2 leads RANDOMIZATION 1:1 by IVRS, OPEN LABEL Strategy B: primary PCI Strategy A: pharmaco-invasive Ambulance/ER ≥75y: ½ dose TNK <75y:full dose no lytic Aspirin Aspirin Antiplatelet and Clopidogrel: Clopidogrel: antithrombin treatment LD 300 mg + 75 mg QD 75 mg QD according to local Enoxaparin: Enoxaparin: standards 30 mg IV + 1 mg/kg SC 0.75 mg/kg SC Q12h Q12h ECG at 90 min: ST resolution ≥ 50% PCI Hospital NO YES immediate angio + angio >6 to 24 hrs rescue PCI if Standard primary PCI PCI/CABG if indicated indicated Primary endpoint: composite of all cause death or shock or CHF or reinfarction up to day 30 F. Van de Werf, ACC 2013 Armstrong PW et al. NEJM, 2013

STUDY PROTOCOL STEMI <3 hrs from onset symptoms, PPCI <60 min not possible, 2 mm ST-elevation in 2 leads RANDOMIZATION 1:1 by IVRS, OPEN LABEL Strategy B: primary PCI Strategy A: pharmaco-invasive After 20% of the planned Ambulance/ER ≥75y: ½ dose TNK <75y:full dose no lytic recruitment, the TNK dose was reduced by Aspirin Aspirin Antiplatelet and Clopidogrel: Clopidogrel: antithrombin treatment 50% among patients ≥75 LD 300 mg + 75 mg QD 75 mg QD according to local Enoxaparin: Enoxaparin: years of age. standards 30 mg IV + 1 mg/kg SC 0.75 mg/kg SC Q12h Q12h ECG at 90 min: ST resolution ≥ 50% PCI Hospital NO YES immediate angio + angio >6 to 24 hrs rescue PCI if Standard primary PCI PCI/CABG if indicated indicated Primary endpoint: composite of all cause death or shock or CHF or reinfarction up to day 30 F. Van de Werf, ACC 2013 Armstrong PW et al. NEJM, 2013

BASELINE CHARACTERISTICS (1) Pharmaco-invasive PPCI (N=948) (N=944) Age (yrs) 59.7 (12.4) 59.6 (12.5) Age ≥75 y (%) 14% 13% Women (%) 21% 22% Weight (kg) 80.5 (14.8) 80.0 (14.9) Killip class (%) I 94% 94% II/III 6% 5% IV <1% <1% Heart rate (bpm) 74.9 (18.4) 75.5 (18.1) Systolic BP (mmHg) 135.0 (22.7) 135.9 (23.3) Infarct location Anterior 48% 46% Inferior 50% 53% Other 2% 2% Data are mean (SD) or % F. Van de Werf, ACC 2013 Armstrong PW et al. NEJM, 2013

BASELINE CHARACTERISTICS (2) Pharmaco-invasive PPCI (N=944) (N=948) Previous MI 9% 10% Previous PCI 6.4% 8.8% Previous CABG <1% <1% Previous congestive heart <1% 2% failure Hypertension 47% 44% Diabetes 12% 13% Data are % F. Van de Werf, ACC 2013 Armstrong PW et al. NEJM, 2013

MEDIAN TIMES TO TREATMENT (min) Rx TNK 62 29 9 100 min 78 min 1st Medical difference Sx onset Randomize IVRS contact Rx PPCI 61 31 86 1 Hour 2 Hours 178 min n=1892 F. Van de Werf, ACC 2013 Armstrong PW et al. NEJM, 2013

MEDIAN TIMES TO TREATMENT (min) Rx TNK 36% Rescue PCI at 2.2h 62 29 9 100 min 64% non-urgent cath at 17h 1st Medical Sx onset Randomize IVRS contact Rx PPCI 61 31 86 1 Hour 2 Hours 178 min n=1892 F. Van de Werf, ACC 2013 Armstrong PW et al. NEJM, 2013

TIMI FLOW RATES P<0.001 P=0.41 TIMI before PCI TIMI after PCI F. Van de Werf, ACC 2013 Armstrong PW et al. NEJM, 2013

INVASIVE PROCEDURES Pharmaco-invasive PPCI P-value (N=944) (N=948) PCI performed 80% 90% <0.001 Stents deployed 96% 96% 0.95 CABG performed 4.7% 2.1% 0.002 F. Van de Werf, ACC 2013 Armstrong PW et al. NEJM, 2013

PRIMARY ENDPOINT TNK vs PPCI Relative Risk 0.86, 95%CI (0.68-1.09) Dth/Shock/CHF/ReMI (%) PPCI 14.3% TNK 12.4% p=0.24 All cause death or shock or CHF or reinfarction up to day 30 F. Van de Werf, ACC 2013 Armstrong PW et al. NEJM, 2013

SINGLE ENDPOINTS UP TO 30 DAYS Pharmaco-invasive PPCI P-value (N=944) (N=948) All cause death (43/939) 4.6% (42/946) 4.4% 0.88 Cardiac death (31/939) 3.3% (32/946) 3.4% 0.92 Congestive heart failure (57/939) 6.1% (72/943) 7.6% 0.18 Cardiogenic shock (41/939) 4.4% (56/944) 5.9% 0.13 Reinfarction (23/938) 2.5% (21/944) 2.2% 0.74 F. Van de Werf, ACC 2013 Armstrong PW et al. NEJM, 2013

IN-HOSPITAL BLEEDING COMPLICATIONS Pharmaco-invasive PPCI P-value (N=944) (N=948) Major non-ICH bleeding 6.5% 4.8% 0.11 Minor non-ICH bleeding 21.8% 20.2% 0.40 Blood transfusions 2.9% 2.3% 0.47 F. Van de Werf, ACC 2013 Armstrong PW et al. NEJM, 2013

Subgroup analyses for primary endpoint within 30 days Relative Risk (95%CI) P(interaction) OVERALL Age <75 years 0.63 ≥75 years Time to randomization 0 to <2h 0.81 ≥2h Male 0.71 Female Systolic blood pressure <100 mmHg 0.16 100 to <140 mmHg 140 to <160 mmHg ≥160 mmHg Killip class I 0.23 II-IV Anterior MI 0.06 Inferior MI Other MI > TNK Better PPCI Better F. Van de Werf, ACC 2013 Armstrong PW et al. NEJM, 2013