1. Current and Future Perspectives on Acute Coronary Syndromes Paul W. Armstrong MD AMI Quebec Montreal October 1, 2010

2. Pivotal Role of Time  Timing of Symptom Onset  Time to 1 st Medical Contact  Time to Reperfusion  Time as Modulator of Rx Effect  Time as Modulator of Rx Choice  Time Interaction & Risk Assessment Strategic Alignment: Paramedical Program, IT & ECG, Molecular Chemistry Coronary Intervention

3. Symptom Recognition Call to Medical System EDCath LabPreHospital Delay in Initiation of Pharmacologic Reperfusion CCU Increasing Loss of Myocytes Treatment Delayed is Treatment Denied Armstrong Collen Antman Circulation 2003 2.4hrs

4. Reperfusion Options for STEMI Pts Step One: Assess Time and Risk Time Since Symptoms Time Required to Initiate Invasive Strategy Risk of STEMI Risk of Lysis

5. 5.04.03.02.01.0<1.0 100.0 80.0 60.0 40.0 20.0 0.0 % Salvageable Ischemic Myocardium ▲---- Duration of occlusion/ Treatment delay (h) 35.0 30.0 25.0 20.0 15.0 10.0 % Rate Aborted MI Reperfusion Relationships: Time & Myocardial Salvage, Lives Saved & Frequency Aborted MI Armstrong,Westerhout, Welsh, Circulation 2009 Absolute 35-day mortality benefit per 1000 Lytic-treated patients

6. Efficacy vs Effectiveness ….. Isn’t All About Time?

7. From Sx onset To PCI Time Mechanical Pharmacological Risk of Rx 93 Self presentation to hospital 911 EMS Infarct specific Patient specific Risk of STEMI Reperfusion Choice Strategy STEMI STEMI NEXUS Armstrong,Westerhout,Welsh, Circulation 2009

8. NSTE ACS: Too Great a Theraputic Burden?  ASA  Anti thrombin(s)  Clopidogrel, Prasugrel  2B /3A  Beta Blocker  ACE inhibitor  Statin  Anti inflammatory  Mechanical Intervention  BMS vs DES

9. GRACE Risk Model Variables  Age (continuous)  Killip class  Blood pressure  ST deviation  Cardiac arrest  Creatinine  Elevated CK-MB / Tn  Heart rate Variables  Age (continuous)  Killip class  Blood pressure  ST deviation  Cardiac arrest  Creatinine  Elevated CK-MB / Tn  Heart rate —Granger et al Archives Int Med 2003 www.umassmed.edu/outcomes/grace C-index = 0.84, validated in clinical trial + registry populations www.statcoder.com/grace.htm Hospital Mortality

10. Mehta S et al. N Engl J Med 2009 Primary Outcome* Stratified by Baseline GRACE Risk Score TIMACS HR 0.65(0.48-0.89) Non ST elev’n ACS n=3031 (1/3) *Death, MI, Stroke @ 6mo Early =14h : Delayed= 50h

11. High – risk ACS (NSTEMI) Opportunities in pre-hospital cardiovascular care Cardiac Arrest ST elevation AMI Seamless pre-hospital diagnosis, triage and treatment Bystander CPR and AED Rapid ACLS response Novel EBM therapies Pre-hospital triage Antiplatelets Anticoagulants Risk assessment and management Welsh & Armstrong Heart 2005

12. Perspectives on Acute Coronary Syndromes  Baseline risk and its evolution  Lesson of subsets and disease heterogeneity  Time and its potential for deception  Dose: Renal function, age, body weight, sex  Bleeding is bad and choice of vascular access site a key modulator  Guidelines are roadmaps: detours may be necessary  Beware of too rapid uptake of high profile meeting presentations  One strategy rarely meets all clinical needs  Patients are partners: helping them make an informed choice is an art a