Current and Future Perspectives on Acute Coronary Syndromes Paul W. Armstrong MD AMI Quebec Montreal October 1, 2010 Pivotal Role of Time Timing of Symptom Onset Time to 1st 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 Treatment Delayed is Treatment Denied 2.4hrs Symptom Recognition Call to Medical System PreHospital ED CCU Cath Lab Delay in Initiation of Pharmacologic Reperfusion Armstrong Collen Antman Circulation 2003 Reperfusion Options for STEMI Pts Step One: Assess Time and Risk Time Since Symptoms Risk of STEMI Risk of Lysis Time Required to Initiate Invasive Strategy % Salvageable Ischemic Myocardium ▲---- 100.0 35.0 80.0 30.0 60.0 25.0 40.0 20.0 20.0 15.0 0.0 % Rate Aborted MI Absolute 35-day mortality benefit per 1000 Lytic-treated patients Reperfusion Relationships: Time & Myocardial Salvage, Lives Saved & Frequency Aborted MI 10.0 <1.0 1.0 2.0 3.0 4.0 5.0 Duration of occlusion/ Treatment delay (h) Armstrong ,Westerhout, Welsh, Circulation 2009 Efficacy vs Effectiveness ….. Isn’t All About Time? Time From Sx onset 9 Self presentation to hospital To PCI STEMI NEXUS Reperfusion Choice 911 EMS 3 Strategy Armstrong ,Westerhout,Welsh, Circulation 2009 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 Hospital Mortality GRACE Risk Model Variables www.statcoder.com/grace.htm www.umassmed.edu/outcomes/grace Age (continuous) Killip class Blood pressure ST deviation Cardiac arrest Creatinine Elevated CK-MB / Tn Heart rate C-index = 0.84, validated in clinical trial + registry populations —Granger et al Archives Int Med 2003 TIMACS Primary Outcome* Stratified by Baseline GRACE Risk Score Non ST elev’n ACS n=3031 HR 0.65(0.48-0.89) (1/3) *Death, MI, Stroke @ 6mo Early =14h : Delayed= 50h Mehta S et al. N Engl J Med 2009 Opportunities in pre-hospital cardiovascular care ST elevation AMI Seamless pre-hospital diagnosis, triage and treatment Risk assessment and management High – risk ACS (NSTEMI) Pre-hospital triage Antiplatelets Anticoagulants Bystander CPR and AED Rapid ACLS response Novel EBM therapies Cardiac Arrest Welsh & Armstrong Heart 2005 Perspectives on Acute Coronary Syndromes a 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