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
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
‐ Astra Zeneca, Bayer, Boehringer Ingelheim, Bristol Myers-Squibb, Eli Lilly, Johnson and Johnson, Pfizer, Portola, Regado, Roche, sanofi aventis
‐ Astra Zeneca, Bayer, Bristol Myers-Squibb, Edwards Lifesciences, Eli Lilly, Medtronic, Roche, sanofi-aventis
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 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)
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?
Rathore SS, et al, Am J Cardiol. 2009 Nov 1;104(9):1198-203 Time (min) 30-d Mortality 1-Year Mortality Adjusted Adjusted 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) 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) 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)
1 year mortality 30 day mortality
N=1932 N=1932
30-day Death, Re-MI, Refractory Ischemia, CHF, Cardiogenic Shock or Major ventricular arrhythmia
0 5 10 15 20 25 30 Days 30 25 20 15 10 5 Primary efficacy endpoint (%) A 25.0% C 23.0% B 24.0%
Armstrong PW. Eur Heart J. 2006 Jul;27(13):1530-8
0 5 10 15 20 25 30 Days 30-day Death / MI (%) 30 25 20 15 10 5 A 13.0% B 6.7% C 4.0% p=0.02 log rank A vs C
Armstrong PW. Eur Heart J. 2006 Jul;27(13):1530-8
Sx to Rand’n<2h n=364 Sx to Rand’n≥2h n=275 Sx to Rand’n≥2h n=234 Sx to Rand’n<2h n=289
Westerhout et al, Am Heart J. 2011 Feb;161(2):283-90
p=0.021 FL<2h versus PCI<2h
Westerhout et al, Am Heart J. 2011 Feb;161(2):283-90
Armstrong PW et al. NEJM, 2013
no lytic
RANDOMIZATION 1:1 by IVRS, OPEN LABEL Ambulance/ER Primary endpoint: composite of all cause death or shock or CHF or reinfarction up to day 30 ECG at 90 min: ST resolution ≥ 50% Standard primary PCI
Aspirin Clopidogrel: LD 300 mg + 75 mg QD Enoxaparin: 30 mg IV + 1 mg/kg SC Q12h
Antiplatelet and antithrombin treatment according to local standards angio >6 to 24 hrs PCI/CABG if indicated immediate angio + rescue PCI if indicated YES NO Strategy A: pharmaco-invasive Strategy B: primary PCI
Aspirin Clopidogrel: 75 mg QD Enoxaparin: 0.75 mg/kg SC Q12h
PCI Hospital STEMI <3 hrs from onset symptoms, PPCI <60 min not possible, 2 mm ST-elevation in 2 leads ≥75y: ½ dose TNK <75y:full dose Armstrong PW et al. NEJM, 2013
no lytic
RANDOMIZATION 1:1 by IVRS, OPEN LABEL Ambulance/ER Primary endpoint: composite of all cause death or shock or CHF or reinfarction up to day 30 ECG at 90 min: ST resolution ≥ 50% Standard primary PCI
Aspirin Clopidogrel: LD 300 mg + 75 mg QD Enoxaparin: 30 mg IV + 1 mg/kg SC Q12h
Antiplatelet and antithrombin treatment according to local standards angio >6 to 24 hrs PCI/CABG if indicated immediate angio + rescue PCI if indicated YES NO Strategy A: pharmaco-invasive Strategy B: primary PCI
Aspirin Clopidogrel: 75 mg QD Enoxaparin: 0.75 mg/kg SC Q12h
PCI Hospital STEMI <3 hrs from onset symptoms, PPCI <60 min not possible, 2 mm ST-elevation in 2 leads ≥75y: ½ dose TNK <75y:full dose
After 20% of the planned recruitment, the TNK dose was reduced by 50% among patients ≥75 years of age.
Armstrong PW et al. NEJM, 2013
Pharmaco-invasive (N=944) PPCI (N=948)
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 II/III IV
94% 6% <1% 94% 5% <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 Inferior Other
48% 50% 2% 46% 53% 2%
Data are mean (SD) or %
Armstrong PW et al. NEJM, 2013
Pharmaco-invasive (N=944) PPCI (N=948) Previous MI
9% 10%
Previous PCI
6.4% 8.8%
Previous CABG
<1% <1%
Previous congestive heart failure
<1% 2%
Hypertension
47% 44%
Diabetes
12% 13%
Data are %
Armstrong PW et al. NEJM, 2013
1 Hour 2 Hours
n=1892
Sx onset
100 min
178 min
1st Medical contact
78 min difference
Randomize IVRS
Armstrong PW et al. NEJM, 2013
1 Hour 2 Hours
n=1892
Sx onset
1st Medical contact Randomize IVRS
Armstrong PW et al. NEJM, 2013
36% Rescue PCI at 2.2h 64% non-urgent cath at 17h
178 min
100 min
TIMI before PCI TIMI after PCI P<0.001 P=0.41
Armstrong PW et al. NEJM, 2013
Pharmaco-invasive (N=944) PPCI (N=948) P-value PCI performed 80% 90% <0.001 Stents deployed 96% 96% 0.95 CABG performed 4.7% 2.1% 0.002
Armstrong PW et al. NEJM, 2013
TNK 12.4% PPCI 14.3% TNK vs PPCI Relative Risk 0.86, 95%CI (0.68-1.09) p=0.24 Dth/Shock/CHF/ReMI (%)
Armstrong PW et al. NEJM, 2013
All cause death or shock or CHF or reinfarction up to day 30
Pharmaco-invasive (N=944) PPCI (N=948) P-value All cause death Cardiac death (43/939) 4.6% (31/939) 3.3% (42/946) 4.4% (32/946) 3.4% 0.88 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
Armstrong PW et al. NEJM, 2013
Pharmaco-invasive (N=944) PPCI (N=948) P-value 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
Armstrong PW et al. NEJM, 2013
> Subgroup analyses for primary endpoint within 30 days
Relative Risk (95%CI) OVERALL Age <75 years ≥75 years P(interaction) 0.63 0.81 0.71 0.16 0.23 0.06 Time to randomization 0 to <2h ≥2h Male Female Systolic blood pressure <100 mmHg 100 to <140 mmHg 140 to <160 mmHg ≥160 mmHg Killip class I II-IV Anterior MI Inferior MI Other MI TNK Better PPCI Better
Armstrong PW et al. NEJM, 2013
Subgroup analyses for primary endpoint within 30 days
Relative Risk (95%CI) Hypertension, Yes P(interaction) 0.34 0.24 0.68 0.13 Diabetes, Yes No Place of randomization, Ambulance Community hospital Before Amendment TNK Better PPCI Better
> >
No Weight, <60 kg 60 to <90 kg ≥90 kg TIMI Risk Score, <5 points ≥5 points After Amendment 0.35 0.71 p=0.07
Armstrong PW et al. NEJM, 2013
Pharmaco-invasive PPCI P-value
TOTAL POPULATION (N=1892) Total stroke fatal stroke Haemorrhagic stroke fatal haemorrhagic stroke 15/939 (1.60%) 7/939 (0.75%) 9/939 (0.96%) 6/939 (0.64%) 5/946 (0.53%) 4/946 (0.42%) 2/946 (0.21%) 2/946 (0.21%) 0.03 0.39 0.04 0.18 POST AMENDMENT POPULATION (N=1503) Total stroke fatal stroke Haemorrhagic stroke fatal haemorrhagic stroke 9/747 (1.20%) 3/747 (0.40%) 4/747 (0.54%) 2/747 (0.27%) 5/756 (0.66%) 4/756 (0.53%) 2/756 (0.26%) 2/756 (0.26%) 0.30 >0.999 0.45 >0.999
Armstrong PW et al. NEJM, 2013
A strategy of fibrinolysis with bolus tenecteplase and contemporary antithrombotic therapy given before transport to a PCI-capable hospital coupled with timely coronary angiography:
within 3 hours of symptom onset who cannot undergo primary PCI within one hour of first medical contact.
Armstrong PW et al. NEJM, 2013
Ezekowitz JA et al. J Am Coll Cardiol. 2009 Jan 6;53(1):13-20.
Patient Risk
Tertiary hospital
Vital Heart Response Contemporary Management of Acute MI
Community hospital
Rescue PCI
Pre-hospital fibrinolysis Pre-hospital triage for PCI
Pre-hospital fibrinolysis
higher lower
Adapted from Welsh et al AHJ, Jan 2003
Pre-hospital ambulance
Transfer for Primary PCI
Pre-hospital triage for in-hospital fibrinolysis
Shavadia et al. CJC, 2013
Metro (n=1990) Nonmetro (n=1602) P Death n,(%) 136 (6.8) 69 (4.3) 0.001 Congestive heart failure n,(%) 129 (6.5) 94 (5.9) 0.448 Cardiogenic shock n,(%) 247 (12.4) 202 (12.6) 0.859 Cardiac arrest n,(%) 227 (11.4) 180 (11.2) 0.872 Re-infarction n,(%) 13 (0.65) 10 (0.62) 0.914 Cerebrovascular event n,(%) Hemorrhage n Ischemic n 21 (1) 9 12 11 (0.67) 8 3 0.838 0.055 Composite of death, re-MI, card arrest and congestive heart failure n,(%) 335 (16.8) 242 (15.1) 0.161
Shavadia et al. CJC, 2013
Multivariable logistic regression model5 of the composite event
5The overall model is significant (LR χ2 (6) = 93.25 with p-value < 0.0001). The model fits the data
well (Hosmer-Lemeshow χ2 (6) = 1.17 with p-value = 0.979; C-statistic=0.66).
Adjusted OR (95% CI) p-value Age (yrs) 1.03 (1.02, 1.04) < 0.001 Hypercholesterolemia 0.74 (0.60, 0.90) 0.003 Diabetes 1.75 (1.38, 2.21) < 0.001 Non-metropolitan site 0.81 (0.50, 1.30) 0.37 Fibrinolysis 0.41 (0.26, 0.67) < 0.0012
Shavadia et al. CJC, 2013
* P <= 0.05 comparison between aborted MI vs. STEMI
* * *
N= 357 1878 206 1005 151 873
Bainey et al. ACC 2013, abstract
0% 5% 10% 15% 20% 25% 30% 35% 1 1-2 2-3 3-4 4-5 5-6 Time of symptom onset to reperfusion therapy
PCI Fibrinolysis Total
P total trend <0.001
Bainey et al. ACC 2013, abstract