managing the acute coronary syndrome: what is new?
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Master Class : 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 Barts and the London School of Medicine and Dentistry - PowerPoint PPT PresentationTRANSCRIPT
Managing the acute coronary syndrome: What is new?
Prof. Adam TimmisBarts and the London School of
Medicine and DentistryUniversity of London
Slide lecture prepared and held by:
Master Class: Advanced CV Risk management in cardiologyJune 17-18, 2011, London
Presentation topic
Declining incidence of Myocardial InfarctionAge-sex-adjusted data from Kaiser Permanente CA
Any MI
NSTEMI
STEMI
• Life-style and risk factors?
↓ smoking
↑ diabetes, diagnosed hypertension, dyslipidaemia
0
10
20
30
40
50
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008
Year
Prop
ortio
n of
Use
(%)
ACE-I/ARB
Thienopyridine
Non-Statin Lipid Lowering
β-Blocker
Statin
0
10
20
30
40
50
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008
B-blockerACE-ARB
Outpatient medication use prior to AMI Kaiser Permanente data CA
• Medication use?
↑ all preventive medication
Rates of diabetes in patients with 1st AMIMINAP data
Potential drivers of reduced AMI rates
What about revascularisation?
• 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
• CABG?
Assessment of the angiographic severity of coronary stenosis is inadequate to accurately predict the time or location of a subsequent coronary occlusionLittle et al. Circulation 1988
PTCA vs medical: Cardiac death or myocardial infarctionKatritsis, D. G. et al. Circulation 2005
Stable angina NSTEMI - 18/12 after RCA, LAD grafts
Summary 1.
• Rates of AMI declining
• Likely consequence of life-style and treatment factors
• Revasc non-contributory
Life Saving Strategies in AMI
1. Prevent pre-hospital death from 1° VF get the patient to a defibrillator ASAP
2. Prevent hospital death from heart failure initiate reperfusion therapy ASAP
3. Prevent late deaths froma) Recurrent ischaemic events
2° prevention therapyb) Lethal arrhythmias
implantable defibrillator
1st episode of VF/1000 pts/hr
33% of people who die from AMI do so before they reach hospital
Sayer J Heart 2002
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
Components of pre-hospital delay in STEMI Frequency distributions using MINAP data for 2004-2005
BHF Doubt Kills Campaignended October 2007
the message!
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
Life Saving Strategies in AMI
1. Prevent pre-hospital death from 1° VF get the patient to a defibrillator ASAP
2. Prevent hospital death from heart failure and cardiogenic shock initiate reperfusion therapy ASAP
3. Prevent late deaths froma) Recurrent ischaemic events
2° prevention therapyb) Lethal arrhythmias
implantable defibrillator
Primary PCI
STEMI: reperfusion therapy
Adjunctive AntiplateletTherapy
• Aspirin 300mg
• Clopidogrel 600mg
• ± Abciximab
Impact of door to balloon time ACC-NCDR Cath PCI Registry: 2005-2006 (n=43,801)
Rathore BMJ (2010)
2.9 (2.8-3.1)
10.3 (10.0-10.7)
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
Kastrati A et al. Eur Heart J 2007;28:2706-2713
DES vs BMS for primary PCI: meta-analysis of RCTs (n=2786)
HR: 0.38 (0.29-0.50)HR: 0.80 (0.48-1.39)
Dual antiplatelet therapy (DAPT) - continue for 12 months after DESRefining 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 ratesGRAVITAS Investigators. JAMA 2011
• Adjust clopidogrel dose according to genotype
Clopidogrel prodrug activated in liver by cytochrome P-450 (CYP) enzymes
Carriers of loss-of-function CYP alleles have same event rates as non-carriersParé G, et al. N Engl J Med 2010
New Inhibitors of the platelet the ADP P2Y12 receptor
Receptor Binding
Prodrug (requires hepatic activation)
Onset of Action
Half life
Clopidogrel Irreversible Yes Slow Long
Prasugrel Irreversible (stronger)
Yes More rapid Long
Ticagrelor Reversible (stronger)
No Rapid Short
Wallentin L et al. N Engl J Med 2009
PLATO: ticagrelor vs clopidogrel in ACS(n=18624)
Reduced risk of CV events with no increase in bleeding risk
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;
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
NSTEMI: emergency treatment
NSTEMI
Non-MI ACS
STEMI
Chest Pain ?cause
Days after presentation
Pro
bab
ility
of
dyi
ng
0
10
20
30
40
50
60
70
80
90
100
03Q1
03Q2
03Q3
03Q4
04Q1
04Q2
04Q3
04Q4
05Q1
05Q2
05Q3
05Q4
Year and quarter
Trea
tmen
t rat
e (%
)
STEMI
NSTEMI
Trop -ve ACS
NSTEMI: don’t under-estimate it
Prognosis: poor
Undertreated
Trials of Invasive vs Conservative Treatment Strategy in NSTEMI
O’Donoghue, M. et al. JAMA 2008;300:71-80
Fox, K. A. A. et al. J Am Coll Cardiol 2010
Routine Versus Selective Invasive Strategy in NSTEMIMeta-Analysis of Individual Patient Data (n=5467)
CV Death or MI Time to 1st Revasc Procedure
Life Saving Strategies in AMI
1. Prevent pre-hospital death from 1° VF get the patient to a defibrillator ASAP
2. Prevent hospital death from heart failure and cardiogenic shock initiate reperfusion therapy ASAP
3. Prevent late deaths froma) Recurrent ischaemic events
2° prevention therapyb) Lethal arrhythmias
implantable defibrillator
Adjusted KM curves: 1 yr survival by number of 2° prevention drugsMINAP discharge data NSTEMI and STEMI 2003-2009
0 180 360
Days after discharge from hospital
0
0.02
0.1
0.04
0.06
0.08
1
2
3
4
Impact of under-utilisation: adjusted HRs (95% CI) for death by discharge regimens that exclude key 2° prevention drugsMINAP discharge data NSTEMI and STEMI 2003-2009
Hazard ratio (95% CI) for death
GPRD: Continuing statin therapy in 12m post ACSN=6607 linked GPRD-MINAP records
Discontinuation of clopidogrel(“non-compliance”) after discharge from hospitalLinked 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)
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.
Life Saving Strategies in AMI
1. Prevent pre-hospital death from 1° VF get the patient to a defibrillator ASAP
2. Prevent hospital death from heart failure and cardiogenic shock initiate reperfusion therapy ASAP
3. Prevent late deaths froma) Recurrent ischaemic events
2° prevention therapyb) Lethal arrhythmias
implantable defibrillator
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
Implantable defibrillator post AMINICE 2007
How it was
Thrombolysis
2° prevention
1° PCI
The revolution for coronary outcomes in east London