ACC Rockies New Role For An Old Friend: Contemporary Insights From The ECG

Transcription

1 ACC Rockies 2012 New Role For An Old Friend: Contemporary Insights From The ECG Paul W. Armstrong, MD Monday March

2 2012 Disclosure Statement Paul W. Armstrong MD Details Research Grants Boehringer Ingelheim sanofi aventis Scios/ Ortho-Biotech Merck Astra Zeneca Eli Lilly GlaxoSmithKline Regado Biosciences Consultant Regado Biosciences Data & Safety Monitoring Boards Roche Orexigen

3 Overview: New Tricks from Old Dogs Ischemic Burden: STE & Non STE Infarct Masquerade Q wave Insights Assessing reperfusion Insights into Rx mechanisms

4 Heart 2007

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7 ASSENT -3: 30-d and 1-yr mortality in patients with 50% and <50% STR at 180 min based on quartiles of baseline STD 28 1st 2nd 3rd 4th % p< p< p< p< day mortality 1-year mortality 50% <50% 50% <50% N= Toma et al Heart 2008

8 90-day composite endpoint according to adherence to ECG entry criteria by infarct location p=0.007 Inferior MI and not met (n = 980) Inferior MI and met (n = 1,337) p=0.021 Other MI and not met (n = 634) Other MI and met (n = 2,658) Tjandrawidjaja et al Eur Heart J. 2007

9 Rates of clinical endpoint (%) Implications of Adherence to ECG entry criteria Placebo Pexelizumab d death 90-d death 90-d composite Met ECG entry criteria (n=3,999) 30-d death 90-d death 90-d composite Did not meet ECG entry criteria (n=1,616) Tjandrawidjaja et al Eur Heart J. 2007

10 What about extent of ST-segment depression?

11 Cum Survival One-year Survival & ST status PARAGON-A No ST dep N=615 1mm ST dep N= mm ST dep N= Follow-up in days Kaul et al JACC 2001

12 % 1-yr Death ST-dep, NT-proBNP and 1-year Mortality *All comparisons p< ST-dep 0 >=2mm 1-1.5mm 0.5mm No ST dep > <=237 NT pro-bnp Westerhout et al JACC 2006

13 Cum Survival / Events The Discharge ECG Death/(re)mi at 6 m NO ST N= P=0.001 P=0.005 ST Normalized N= ST persisted N= Days Herhsi et al EHJ 02

14 Overview: New Tricks from Old Dogs Ischemic Burden: STE & Non STE Infarct Masquerade Q wave Insights Assessing reperfusion Insights into Rx mechanisms

15 3.5 mm 3 mm Baseline ECG Random ization TNK 90 min Post TNK ECG Pre Cath ECG Rescue PCI Post Cath ECG Not done 153 Discharge ECG 03:23 04:06 04:20 05:44 05:45 06:53 08:40 15 Sep 10

16 Baseline 90 min

17 What about Q waves at time of presentation?

18 Cumulative death/chf/shock, % Baseline Q Wave: Death/ CHF/ Shock Baseline Q-wave (n= 2514) p(logrank)< No Baseline Q-wave (n=2016) Days to follow-up Armstrong et al 2009 JACC

19 Baseline Q Wave & Time Sx onset to PCI: 90-Day Outcomes Death HR (95%CI) Baseline Q-wave A: 1.78 ( ), p=0.002 Sx to PCI > 3 hr A: 1.35 ( ), p=0.078 Death/CHF/shock Baseline Q-wave A: 1.90 ( ), p<0.001 Sx to PCI > 3 hr A: 1.42 ( ), p= Armstrong et al 2009 JACC

20 Time vs. Q for risk stratification: Men Time to PCI Q-wave p<0.01 p< Kaul et al ESC 2010

21 Kaul et al ESC 2010 What about Time and Women? p<

22 Overview: New Tricks from Old Dogs Ischemic Burden: STE & Non STE Infarct Masquerade Q wave Insights Assessing reperfusion Insights into Rx mechanisms

23 6 mm 12 mm Baseline ECG Random ization TNK 90 min Post TNK ECG Pre Cath ECG Rescue PCI Post Cath ECG Discharge ECG :40 08:51 08:51 10:28 10:42

24 Aborted MI Pre Post Reperfusion

25 Aborted MI subgroup analysis 15% 12% 9% 6% 3% 0% 7.5% p=ns 10.8% 30d death/reinfarction/refractory ischemia 1.0% 6.1% Death at 30d ST n=130 p= % 2.2% In-hospital re-infarction ST n=80 p=ns Taher et al JACC 2004

26 Aborted MI subgroup analysis 15% 12% 9% 6% 3% 0% 7.5% p=ns 10.8% 30d death/reinfarction/refractory ischemia 1.0% 6.1% Death at 30d ST n=130 p= % 2.2% In-hospital re-infarction ST n=80 p=ns Taher et al JACC 2004

27 90-day Dth/CHF/Shock Buller et al Circulation 2008 ST Resolution & Outcomes 30-min post-pci ST-resolution revealed striking risk gradation in primary PCI STEMI pts enrolled in APEX AMI No ST resolution n= % 10.0 Partial ST resolution n= % Complete ST resolution n= % 90

28 90-day Dth/CHF/Shock Buller et al Circulation 2008 ST Resolution & Outcomes 30-min post-pci ST-resolution revealed striking risk gradation in primary PCI STEMI pts enrolled in APEX AMI No ST resolution n= % 10.0 Partial ST resolution n= % Complete ST resolution n= % 90

29 Adjusted* hazard for 90-day Death/Shock/CHF HR (95% CI) ST res 50% and ST res 50% (Reference group) ST res 50% & ST res <50% 1.4 p = ST res <50% & ST res 50% 1.6 p = ST res <50% & ST res <50% 2.4 p < *Adjusted for age, sex, hypertension, prior MI, Killip Class, SBP, HR, baseline ST dev, Time Sx to PCI, pre-pci TIMI, culprit artery, 3 V disease, post-pci TIMI Flow EHJ 2010

30 EHJ 2010 Selected baseline & angiographic characteristics ST resolution 50% ST resolution <50% ST 50% ST <50% ST 50% ST <50% (n = 2,856) (n = 560) (n = 730) (n = 583) Age, yr, median 60 64* 61 65* Female, % 22 29* 19 27* Hypertension, % 47 52* Diabetes, % 13 17* 18 23* Killip class >I, % 9 12* Time to PCI, hr in 4 patients with ST-depression resolution <50%

31 Selected baseline & angiographic characteristics ST resolution 50% ST resolution <50% ST 50% ST <50% ST 50% ST <50% (n = 2,856) (n = 560) (n = 730) (n = 583) Age, yr, median 60 64* 61 65* Female, % 22 29* 19 27* Hypertension, % 47 52* Diabetes, % 13 17* 18 23* Killip class >I, % 9 12* Time to PCI, hr ST,mm, median * ST,mm, median * Post-PCI TIMI 3,% 93 91* 87 80* Triple vessel dz,% 13 19* EHJ 2010

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33 Cumulative incidence (%) Primary efficacy endpoint over time (composite of CV death, MI or stroke) Cumulative incidence (%) Clopidogrel Ticagrelor Clopidogrel 5.28 Ticagrelor HR 0.88 (95% CI ), p= HR 0.80 (95% CI ), p< No. at risk Days after randomisation Days after randomisation * Ticagrelor 9,333 8,942 8,827 8,763 8,673 8,543 8,397 7,028 6,480 4,822 Clopidogrel 9,291 8,875 8,763 8,688 8,688 8,437 8,286 6,945 6,379 4,751 *Excludes patients with any primary event during the first 30 days

34 Survival Probability Armstrong et al Circulation 2011 One-year CV-death/MI by ST-deviation resolution >50% (n=3135) 6.4% <50% (n=1556) 8.9% p(logrank)=0.001 Time to event (days)

35 Survival Probability Armstrong et al Circulation 2011 One-year CV-death/MI by Rx & ST-deviation resolution Ticagrelor > 50% (n=1565) Clopidogrel > 50% (n=1570) Clopidogrel < 50% (n=770) Ticagrelor <50% (n=786) P = 0.10(study treatment / ST-dev res))= % 7.7% 8.7% 9.1% Time to event (days)

36 ST-D Resolution 50% Ticagrelor Clopidogrel % Sx-R </=3 Sx-R > 3-6 Sx-R > 6 Armstrong et al Circulation 2012

37 Cumulative incidence (%) Primary efficacy endpoint over time (composite of CV death, MI or stroke) Cumulative incidence (%) Clopidogrel Ticagrelor Clopidogrel 5.28 Ticagrelor HR 0.88 (95% CI ), p= HR 0.80 (95% CI ), p< No. at risk Days after randomisation Days after randomisation * Ticagrelor 9,333 8,942 8,827 8,763 8,673 8,543 8,397 7,028 6,480 4,822 Clopidogrel 9,291 8,875 8,763 8,688 8,688 8,437 8,286 6,945 6,379 4,751 *Excludes patients with any primary event during the first 30 days

38 There are New Tricks from Old Dogs ECG is a renaissance tool Grossly underappreciated bioassay Prognostically powerful Unique insights into state of play AMI Promptly responsive to interventions Insights into Rx choices / Mechanisms Valuable Metric in Clinical Trials