Managing the acute coronary syndrome: What is new?

1. MasterClass: Advanced CV Risk management in cardiology June 17-18,2011, London Presentation topic Managing the acute coronary syndrome: What is new? Slide lecture prepared and held by: Prof. Adam Timmis Bartsand the London School of Medicineand Dentistry University of London

2. Declining incidence of Myocardial InfarctionAge-sex-adjusted data from Kaiser Permanente CA Any MI NSTEMI STEMI

3. Potential drivers of reduced AMI rates Rates of diabetes in patients with 1st AMI MINAP data • Life-style and risk factors? • ↓ smoking • ↑ diabetes, diagnosed hypertension, dyslipidaemia Outpatient medication use prior to AMI Kaiser Permanente data CA • Medication use? • ↑ all preventive medication B-blocker ACE-ARB

4. What about revascularisation? PTCA vs medical: Cardiac death or myocardial infarction Katritsis, D. G. et al. Circulation 2005 • PCI? “88% of patients believed that PCI would reduce their risk for MI, and 82% believed that it would reduce their risk for death” Rothberg MB et al. Ann Intern Med 2010 Stable angina NSTEMI - 18/12 after RCA, LAD grafts • CABG? Assessment of the angiographic severity of coronary stenosis is inadequate to accurately predict the time or location of a subsequent coronary occlusion Little et al. Circulation 1988

5. Summary 1. • Rates of AMI declining • Likely consequence of life-style and treatment factors • Revasc non-contributory

6. Life Saving Strategies in AMI • Prevent pre-hospital death from 1° VF • get the patient to a defibrillator ASAP • Prevent hospital death from heart failure • initiate reperfusion therapy ASAP • Prevent late deaths from • Recurrent ischaemic events • 2° prevention therapy • Lethal arrhythmias • implantable defibrillator

7. 1st episode of VF/1000 pts/hr 33% of people who die from AMI do so before they reach hospital Sayer J Heart 2002

8. Components of pre-hospital delay in STEMI Frequency distributions using MINAP data for 2004-2005 • Time to call for help accounts for most of the variation in pre-hospital delay. Culprits • Older people (>70 yrs) • Women • People with diabetes • Pain onset in early hours • Pain at w/e

9. BHF Doubt Kills Campaign ended October 2007 the message!

10. Summary 2. • 33% of all AMI deaths occur out-of-hospital • Shortening the time to call for help the single most important way to save lives in AMI • Public awareness campaigns never been shown to work

11. Life Saving Strategies in AMI • Prevent pre-hospital death from 1° VF • get the patient to a defibrillator ASAP • Prevent hospital death from heart failure and cardiogenic shock • initiate reperfusion therapy ASAP • Prevent late deaths from • Recurrent ischaemic events • 2° prevention therapy • Lethal arrhythmias • implantable defibrillator

12. STEMI: reperfusion therapy Primary PCI • Adjunctive Antiplatelet • Therapy • Aspirin 300mg • Clopidogrel 600mg • ± Abciximab

13. 10.3 (10.0-10.7) 2.9 (2.8-3.1) Impact of door to balloon timeACC-NCDR Cath PCI Registry: 2005-2006 (n=43,801) Rathore BMJ (2010)

14. Culprit only vs complete revascularisation in STEMI: meta-analysis J Thromb Thrombolysis 2011 • Complete Revasc • No benefit for mortality • No benefit for recurrent MI • Reduced need for repeat revasc

15. DES vs BMS for primary PCI: meta-analysis of RCTs (n=2786) HR: 0.80 (0.48-1.39) HR: 0.38 (0.29-0.50) Kastrati A et al. Eur Heart J 2007;28:2706-2713

16. Dual antiplatelet therapy (DAPT) - continue for 12 months after DES • Refining aspirin/clopidogrel treatment regimens to protect against late thrombosis • Prolonged DAPT for >12 months No effect on 2 yr event rates Park S-J et al. N Engl J Med 2010 • Titrate clopidogrel dose against platelet function testing No effect on 6 month event rates GRAVITAS Investigators. JAMA 2011 • Adjust clopidogrel dose according to genotype • Clopidogrelprodrug activated in liver by cytochrome P-450 (CYP) enzymes Carriers of loss-of-function CYP alleles have same event rates as non-carriers • Paré G, et al. N Engl J Med 2010

17. New Inhibitors of the platelet the ADP P2Y12 receptor

18. PLATO: ticagrelor vs clopidogrel in ACS (n=18624) Wallentin L et al. N Engl J Med 2009 Reduced risk of CV events with no increase in bleeding risk

19. 1° PCI: 1 year mortality by baseline CRP and adjunctive treatment with abciximab or placebo. Pooled analysis of 4 ISAAR trials (n=4847) Iijima R et al. Heart 2009;

20. NSTEMI: emergency treatment PCI: moderate high risk 1. Aspirin + clopidogrel ± GP IIb/IIIa inhibitor 2. LMWH - now fondaparinux (factor Xa inhibitor) 3. Anti-ischaemic drugs (BB, nitrates) 4. ± Angiography ± PCI

21. NSTEMI Non-MI ACS STEMI Chest Pain ?cause Probability of dying Days after presentation NSTEMI: don’t under-estimate it Prognosis: poor Undertreated

22. Trials of Invasive vs Conservative Treatment Strategy in NSTEMI O’Donoghue, M. et al. JAMA 2008;300:71-80

23. Routine Versus Selective Invasive Strategy in NSTEMI Meta-Analysis of Individual Patient Data (n=5467) CV Death or MI Time to 1st Revasc Procedure Fox, K. A. A. et al. J Am Coll Cardiol 2010

24. Life Saving Strategies in AMI • Prevent pre-hospital death from 1° VF • get the patient to a defibrillator ASAP • Prevent hospital death from heart failure and cardiogenic shock • initiate reperfusion therapy ASAP • Prevent late deaths from • Recurrent ischaemic events • 2° prevention therapy • Lethal arrhythmias • implantable defibrillator

25. 0.1 1 0.08 2 0.06 0.04 3 0.02 4 0 0 180 360 Days after discharge from hospital Adjusted KM curves: 1 yr survival by number of 2° prevention drugs MINAP discharge data NSTEMI and STEMI 2003-2009

26. Hazard ratio (95% CI) for death Impact of under-utilisation: adjusted HRs (95% CI) for death by discharge regimens that exclude key 2° prevention drugs MINAP discharge data NSTEMI and STEMI 2003-2009

27. GPRD: Continuing statin therapy in 12m post ACS N=6607 linked GPRD-MINAP records

28. Discontinuation of clopidogrel(“non-compliance”) after discharge from hospital Linked MINAP-GPRD registries (n=8445) • Median Duration of therapy: 12m • Hazard of death/AMI • clopidogrel vs no clopidogrel HR 0.57 (0.50-0.65) • discontinuation vs continuation HR 2.62 (2.17-3.17)

29. Summary 4. • 2° prevention therapy - additive beneficial effects on survival • diminishing efficacy probably caused by non-adherence to treatment in primary care • non-adherence to clopidogrel in linked GPRD-MINAP registries more than doubles the risk of recurrent myocardial infarction or death during the first year.

30. Life Saving Strategies in AMI • Prevent pre-hospital death from 1° VF • get the patient to a defibrillator ASAP • Prevent hospital death from heart failure and cardiogenic shock • initiate reperfusion therapy ASAP • Prevent late deaths from • Recurrent ischaemic events • 2° prevention therapy • Lethal arrhythmias • implantable defibrillator

31. Implantable defibrillator post AMI NICE 2007 2° prevention • Late cardiac arrest VT/VF • Sustained VT with syncope • Sustained VT and LV ejection fraction <35% 1° prevention • AMI >4 weeks previously • LV ejection fraction <30% and QRS >120msec • LV ejection fraction <35% and non-sustained VT on Holter

32. The revolution for coronary outcomes in east London How it was Thrombolysis 2° prevention 1° PCI