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DESCRIPTION
Acute Coronary Syndromes From the Emergency Department to the Coronary Care Unit to the Office. WELCOME! Please take a moment to complete the short pre -program survey in your packet. Your participation will help us assess the effectiveness of this program - PowerPoint PPT PresentationTRANSCRIPT
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WELCOME! Please take a moment to complete the short pre-
program survey in your packet.
Your participation will help us assess the effectiveness of this program and shape future CME activities.
Thank you.
Acute Coronary SyndromesFrom the Emergency Department to the
Coronary Care Unit to the Office
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Faculty Disclosures
The faculty reported the following relevant financial relationships that they or their spouse/partner have with commercial interests:
• Presenting Physician, MDCategory – Disclosures
TO BE FILLED IN BY PRESENTING PHYSICIAN
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Steering Committee Disclosures
The Steering Committee reported the following relevant financial relationships that they or their spouse/partner havewith commercial interests:
• Deepak L. Bhatt, MD, MPH, FACC, FAHA, FSCAI: Principal Investigator: Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, The Medicines Company
• Charles V. Pollack Jr., MA, MD, FACEP, FAAEM, FAHA: Honorarium: Merck, Forest
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Non-faculty Disclosures
Non-faculty content contributors and/or reviewers reported the following relevant financial relationships that they or their spouse/partner have with commercial interests:
• Barry Watkins, PhD; Bradley Pine; Blair St. Amand; Jay Katz; Dana Simpler, MD: Nothing to Disclose
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Educational Objectives
This program is designed to address the following IOM competencies: provide patient-centered care and employ evidence-based practice. At the conclusion of this activity, participants should be able to:
• Adopt ischemic risk assessment stratification strategies to choose the best course of action to manage patients with acute chest pain syndrome
• Assess and stratify bleeding risk after antiplatelet treatment is initiated
• Make treatment choices based on an understanding of the different mechanisms of action among antithrombotic agents and on pertinent clinical trial results
• Analyze pharmacologic and clinical trial results of newer antithrombotic agents to determine how best to match treatment options with patients to achieve optimal clinical outcome
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Key Considerations for Clinical Management of ACS
• Need for differential diagnosis of the spectrum of ACS• Fundamental aspects of management of acute chest pain
– Elements for optimal early hospital care• The importance of risk stratification to guide practice decisions
– Options: initial conservative or invasive strategy – If invasive strategy, rationale for early catheterization
• The expanded field of existing antiplatelet treatment options– Clopidogrel, prasugrel, ticagrelor
• Emerging antiplatelet/anticoagulant therapies for ACS– Strong contender: very low dose rivaroxaban
• Standards of treatment for STEMI• The need to balance anti-ischemic effects versus bleeding risk• The growing importance of quality outcomes in ACS
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Chest Pain Case
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Chest Pain CaseInitial Presentation
• 68-year-old female presents to the Emergency Department at 8:45 am
• Epigastric pain radiating to left shoulder for two hours; onset was with exertion but continued at rest
• Initial ECG shows widespread STT wave anomalies with T wave inversions (V2-V6)
• ECG shows marked ST-segment depression in the lateral precordial leads (V5, V6)
• CVD History: Suspected CAD with abnormal stress test, but declined catheterization one year ago; treated with beta-blockers and long-acting nitrates
• Additional Medical History: Significant only for hypertension
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Chest Pain CaseInitial ECG
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Chest Pain CaseTreatment Stratification Issues
• Choice of therapy depends at least in part on selection of management strategy for next 24h:– Invasive or conservative?
– Patient’s creatinine clearance is 45 cc/min, her first troponin is negative, and she is not anemic
– Once decided, medical therapy that supports that approach should be initiated:• Anticoagulant?
- Which one? What dose?• Oral antiplatelet (beyond aspirin)?
- Which one? What dose?• GP IIb/IIIa antagonist?
- Small or large molecule? What dose?• Beta blocker?
- IV or PO?
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Chest Pain CaseInitial Evaluation
• Two hours later, repeat troponin assay is positive, and patient’s diagnosis is changed from UA to NSTEMI
• Plan is to take her to cath lab as first case tomorrow morning if she remains stable and pain free
• What are your choices of anticoagulation, antiplatelet, and beta-blocker therapy?
• What therapy might you add (or change) in the cath lab?
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Acute Coronary Syndromes
Clinical Spectrum and Presentation
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Acute Coronary SyndromesScope of the Problem
• CHD is the leading cause of death in the US; 814,000 deaths in 2007
• 1,350,000 annual new or recurring ACS events annually
• 34% of those with a coronary event die within a year
• 14% of STEMI patients are rehospitalized within 30 days
• Direct and indirect cost of CHD is $287,000,000,000
• Hospital adherence to ACC/AHA ACS treatment guidelines is only 74%
Roger VT et al. Circulation. 2011;123:e18-e209Lloyd-Jones D et al. Circulation. 2010;121:e46-e215.
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Acute Coronary Syndromes
• Common Features of ACS– Similar pathophysiology– Similar presentation and early management rules
• Differentiating Features– Unstable Angina
• Non-occlusive thrombus• No diagnostic ECG changes, but ischemic ST-T changes confer higher risk• Normal cardiac enzymes
– NSTEMI• Occluding thrombus sufficient to cause myocardial damage• No diagnostic ECG changes, but ischemic ST-T changes: higher risk• Elevated cardiac enzymes
– STEMI• Complete thrombus occlusion• ST elevation or new LBBB• Elevated cardiac enzymes• More severe symptoms
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Mortality in Acute Coronary SyndromesDeath from Hospital Admission to 6 Months
16
12
8
4
00 30 60 90 120 150 180
% M
orta
lity
DaysFox KA et al. BMJ. 2006;333:1091.
STEMI
NSTEMI
UA
GRACE n=43,810
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Risk Stratification and Early Hospital Care
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Management of Acute Chest Pain SyndromeRole of the Emergency Physician
• Stabilization – When required
• Differential Diagnosis of ACS – “Atypical is the new typical”
• Prompt STEMI Management– ~15% of our ACS population
• Risk Stratification of UA and NSTEMI– >50% of acute chest pain patients don’t have ACS
– Of those who have ACS, fewer than 30% are at high ischemic risk
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Acute Coronary SyndromesRisk Stratification
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Chest Pain Syndrome Suggestive of Ischemia
• 12 lead ECG
• Obtain initial cardiac enzymes
• Electrolytes, CBC lipids, BUN/ creatinine, glucose, coags
• Chest x-ray
Immediate Assessment within 10 Minutes
• Establish diagnosis
• Read ECG
• Identify complications
• Assess for reperfusion
Initial Labsand Tests
Emergent Care
History & Physical
• IV access
• Cardiac monitoring
• Oxygen
• Aspirin
• Nitrates
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“Dynamic Risk Stratification” Tools
• History and physical• Standard ECG and non-standard ECG leads
- 15-lead ECGs should perhaps become “standard” in all but very-low-risk patients• Biomarkers
- CK-MB, troponins I and T, myoglobin- High-sensitivity troponin
• Non-invasive imaging- Echocardiogram- Stress testing- Technetium-99m-sestamibi
• Invasive imaging– Cardiac computed tomography angiography (CCTA)
• Predictive indices/schemes- Better as research tools than for real-time clinical decision-making
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PRESENTATION
TIMI RISK SCORE for UA/NSTEMIRisk Algorithms: TIMI, GRACE, PURSUIT;The Preponderance of Evidence Favors the TIMI Score
HISTORICAL
Age ≥ 65 ≥ 3 CAD risk factors(FHx, HTN, ↑ chol, DM, active smoker)Known CAD (stenosis ≥ 50%)ASA use in past 7 days
Recent (≤ 24H) severe angina↑ cardiac markersST deviation ≥ 0.5 mm
RISK SCORE = Total Points (0-7)
RISKSCORE
DEATHOR MI
DEATH, MI, ORURGENT REVASC
0/1 3 5 2 3 8 3 5 13 4 7 20 5 12 26 6/7 19 41
*Entry criteria: UA or NSTEMII defined as ischemic pain at rest within past 24H, with evidence of CAD (ST segment deviation or elevated cardiac marker)
Antman EM et al. JAMA. 2000;284:835-842.
RISK OF CARDIAC EVENTS (%) BY 14 DAYS IN TIMI 11B
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Anterior ST Segment DepressionClassifications
Unstable angina
TIMI flow grade 2/3 in culprit artery
NSTEMI
- Troponin + Troponin
STEMI
+ Troponin
TIMI flow grade 0/1 in culprit artery
Gibson CM et al. 2008 AHA Scientific Sessions
Anterior ST-segment depression
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Troponin Levels Predict Risk of Mortality in UA/NSTEMI
Antman EM et al. N Engl J Med. 1996;335:1342-1949.
1.01.7
3.4 3.7
6.0
7.5
0
1
2
3
4
5
6
7
8
0 to <0.4 0.4 to <1.0 1.0 to <2.0 2.0 to <5.0 5.0 to <9.0 ≥ 9.0
Mor
talit
y at
42
days
; % o
f pat
ient
s
831 174 148 134 50 67
%%
%%
%
%
Cardiac troponin I (ng/mL )
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Acute CoronarySyndromesEarly Hospital Care
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Optimal Upstream Management ofIschemic Risk Assessment
• Basis for assessment– “Pain story”– Background CVD risk– ECG– Troponin elevation in pertinent time frame– Predictive risk score
• Options– Antiplatelet therapy increasingly important as ischemic risk increases– UFH and enoxaparin established– Bivalirudin and fondaparinux: New options that are non-inferior
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Early Invasive Initial Conservative
Braunwald E et al. Available at: www.acc.org.Bowen WE, McKay RG. N Engl J Med. 2001;344:1939-1942.
* Also known as Q-wave MI† Also known as non-Q-wave MI
Treatment of Acute Coronary Syndrome
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Acute Therapy
• Oxygen, Bed Rest
• ECG Monitoring
• Nitroglycerin
• Beta Blockers
• ACE Inhibitors
• Antiplatelet Therapy
• Anticoagulant Therapy
Current Medical Management ofUnstable Angina and NSTEMI
Maintenance Therapy
• Antiplatelet Therapy
• Beta Blockers
• Calcium Channel Blockers
• Lipid-lowering Agents
• ACE Inhibitors
• Oral Anticoagulant Therapy
Braunwald E et al. Available at: www.acc.org.
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Acute Coronary Syndrome
Procedural Considerations:Initial Conservative or Invasive Strategy –
Based on Risk Assessment
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Conservative Therapy Option for UA/NSTEMIEarly Revascularization or PCI Not Planned
• Antiplatelet therapy– Aspirin– Clopidogrel
• MONA + BAH (LMW or UFH)– Morphine, Oxygen, Nitroglycerin, Aspirin + Beta Blocker, ACEI, Heparin
(Morphine has only Class IIa recommendation due to increased mortality risk – CRUSADE)
• Glycoprotein IIb/IIIa inhibitors– Only in certain circumstances
• Planning PCI, elevated troponin
• Surveillance in hospital– Serial ECGs– Serial cardiac markers
Anderson JL ete al. Circulation. 2007;116:e148-e304
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Invasive Therapy Option for UA/NSTEMI
• Coronary angiography and revascularization within 12 to 48 hours after presentation to ED
• For high-risk ACS – MONA + BAH (LMW or UFH)– Morphine, Oxygen, Nitroglycerin, Aspirin + Beta Blocker, ACEI, Heparin (Morphine has only Class IIa recommendation due to increased mortality risk–CRUSADE)– Antiplatelet therapy
Aspirin; thienopyridine (clopidogrel or prasugrel) 20% reduction in death/MI/Stroke PCI + BMS: at least 1 month, ideally 1 year PCI + DES: at least 1 year
– Glycoprotein IIb/IIIa inhibitorAnderson JL et al. Circulation. 2007;116:e148-e304
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ACCF/AHA Guidelines 2011 Focused UpdateEarly Invasive Strategies
High-risk patients with:- Refractory ischemia - Recurrent angina/ischemia- Elevated cardiac biomarkers (T)- New ST-segment depression- New CHF or worsening MR- High-risk on non-invasive testing- LV dysfunction (EF <40%)- Hemodynamic instability- Sustained VT- Diabetics with single vessel disease- Mild to moderate kidney disease- PCI within 6 months, prior CABG high-risk score - Not in low-risk women
I IIa IIb III
Wright RS et al. Circulation. 2011;123:2022-2060
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Time (months)0 1 2 3 4 5 6
0
4
8
12
16
20
% P
atie
nts
Conservative:
Invasive:
O.R 0.7895% CI (0.62, 0.97)P=0.025
19.4%
15.9%
TACTICS: Primary EndpointDeath, MI, Rehospitalized for ACS at 6 Months
Cannon CP et al. N Engl J Med. 2001;344:1879-1887.
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Updated Meta-analysis: Mortality
Bavry, AA et al. J Am Coll Cardiol. 2006;48:1319-1325.
Study
FRISC-II
TRUCS
TIMI-18
VINO
RITA-3
ISAR-COOL
ICTUS
Deaths, n Follow-upInvasive Conservative Months
45 67 24
3 9 12
37 39 6
2 9 6
102 132 60
0 3 1
15 15 12
0.1 1 10FavorsEarly InvasiveTherapy
FavorsConservativeTherapy
Overall RR (95% CI)0.75 (0.63-0.90)
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Invasive StrategyRationale for Early
Catheterization
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*Low/intermediate risk=GRACE score <140 High risk=GRACE score ≥140
TIMACS Rates of death, MI, or stroke within 6 months according to GRACE risk level and HR (95% CI), early versus delayed invasive strategy
Mehta SR et al. N Engl J Med. 2009;310:2165-2175
Early (%) Delayed (%) HR (95% CI) P
Low/Intermediate(n=2070) 7.6 6.7 1.12 (0.88–1.56) 0.48
High (n=961) 13.9 21.0 0.65 (0.48–0.89) 0.006
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CRUSADE Registry Mortality Rates by Early Catheterization
Bhatt DL et al. JAMA. 2004;292:2096-2104..
10
6
4
2
0
8
0.7
2.3
1.1
2.5
3.9
8.6Early Catheterization
No Early Catheterization
% In
-hos
pita
l Mor
talit
y
Low(n=4326)
Moderate(n=4492)
High(n=9108)
Modified PURSUIT Risk Category
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Antithrombotic Therapy in ACS
Evolving Antiplatelet Therapies
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Months of Follow-up
Yusuf S et al. N Engl J Med. 2001;345:494-502.
CURE Study Primary End Point: MI/Stroke/CV Death
Clopidogrel + Aspirin(n=6259)
Placebo + Aspirin(n=6303)
P<0.001n=12,562
3 6 90 12
20%Relative RiskReduction
0.12
0.14
0.10
0.06
0.08
0.00
0.04
0.02Cum
ulat
ive
Haza
rd R
ate
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CREDOLong-Term (1 Year) Benefits of Clopidogrel in PCI Patients
MI, stroke, or death – ITT population
* Plus ASA and other standard therapies Steinhubl S et al. JAMA. 2002;288:2411-2420.
Com
bine
d en
dpoi
nt o
ccur
renc
e (%
)
Months from randomization
27% RRRP=0.02
Placebo*Clopidogrel*
0
5
10
15
8.5%
11.5%
0 3 6 9 12
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Primary Endpoint (MI/Stroke/CV Death) in Patients with Previous MI, IS, or PAD*CHARISMA: “CAPRIE-like Cohort”
RRR: 17.1 % (95% CI: 4.4%, 28.1%)P=0.01
Prim
ary
Outc
ome
Even
t Rat
e (%
)
0
2
4
6
8
10
Months Since Randomization 0 6 12 18 24 30
Clopidogrel + ASAPlacebo + ASA
n=9,478
* Post hoc analysis
Bhatt DL et al. J Am Coll Cardiol. 2007;49:1982-1988.
8.8%
7.3%
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Days
TRITON – TIMI 38 CV Death, MI, Stroke
0
5
10
15
0 30 60 90 180 270 360 450
HR 0.81(0.73-0.90)P=0.0004
Prasugrel
Clopidogrel
Prim
ary
Endp
oint
(%)
12.1(781)
9.9 (643)
NNT= 46
ITT= 13,608 LTFU = 14 (0.1%)
Wiviott SD et al. N Engl J Med. 2007;357:2001-2005.
HR 0.80P=0.0003
HR 0.77P=0.0001
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PLATO: Kaplan-Meier Estimate of Time to First Primary Efficacy Event (Composite of CV Death, MI or Stroke)
No. at risk
ClopidogrelTicagrelor
9,2919,333
8,5218,628
8,3628,460
8,124
Days after randomisation
6,7436,743
5,0965,161
4,0474,147
0 60 120 180 240 300 360
1211109876543210
13Cu
mul
ativ
e in
cide
nce
(%)
9.8
11.7
8,219
HR 0.84 (95% CI 0.77–0.92), p=0.0003
Clopidogrel
Ticagrelor
HR = hazard ratioCI = confidence interval
Wallentin L et al. N Engl J Med. 2009;361:1045-1057
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Glycoprotein IIb/IIIa Inhibitors
• Only indicated in highest risk UA/NSTEMI patients (dynamic changes on ECG, elevated biomarkers, electrical instability) and/or in whom early PCI is planned
• Abciximab is a choice if early angiography and PCI are planned
• Eptifibatide or tirofiban might be indicated when no PCI planned
• Initiate in conjunction with your cardiologist
• Discontinue anticoagulant therapy after PCI
• Use of glycoprotein IIb/IIIa inhibitors is on the decline
Anderson JL et al. J Am Coll Cardiol. 2007;50:e1-e157.Wright RS et al. Circulation. 2011;123:2022-2060
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Antithrombotic Therapy in ACS
Emerging Therapies
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Key Investigational Antithrombotic Drugs
•Factor Xa inhibitors
–Rivaroxaban
–Apixaban
•PAR-1 thrombin inhibitors
–Vorapaxar
–Atopaxar
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RIVAROXABAN: ATLAS ACS 2 TIMI 51Primary Efficacy Endpoint: CV Death / MI / Stroke
Mega JL et al. N Engl J Med. 2012;366:9-19.
0
2
4
6
8
10
12
0 4 8 12 16 20 24
Months After Randomization
Rivaroxaban(both doses 2.5
mg bid and 5 mg bid)
HR 0.84 (0.74-0.96)
mITT p = 0.008ITT p = 0.002
ARR 1.8%NNT = 56
10.7%
8.9%
Placebo
5113 4307 3470 2664 1831 1079 42110229 8502 6753 5137 3554 2084 831
PlaceboRivaroxaban
2 Yr KM Estimate
No. at Risk
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Estim
ated
Cum
ulat
ive
inci
denc
e (%
)RIVAROXABAN: ATLAS ACS 2 TIMI 51Efficacy Endpoints: Very Low Dose 2.5 mg BIDPatients Treated with Aspirin + Thienopyridine
4.2%10.4%PlaceboPlacebo
0 24
Cardiovascular Death
Months
CV Death / MI / Stroke
0 24Months
HR 0.84
mITT p=0.04
ITTp=0.01
HR 0.66
mITTp<0.001
ITTp<0.001
2.5%
9.0%
Rivaroxaban2.5 mg BID
Rivaroxaban2.5 mg BID
NNT = 71 NNT = 59
12 12
12%
5%
Mega JL et al. N Engl J Med. 2012;366:9-19.
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RIVAROXABAN: ATLAS ACS 2 TIMI 51 Treatment Emergent Fatal Bleeds and ICH
Adapted from Mega JL et al. N Engl J Med. 2012:336:9-19.
0.2 0.2
0.1
0.4
0.1
0.4
0.7
0.2
0.1
0
0.2
0.4
0.6
0.8
1
1.2
Fatal ICH Fatal ICH
Placebo2.5 mg Rivaroxaban5.0 mg Rivaroxaban
n=4 n=5 n=8n=9 n=6 n=15
P = NS for all comparisons
n=5 n=18n=14
P = NS for Riva vs PlaceboP = NS for Riva 5 vs PlaceboP = NS for Riva 2.5 vs PlaceboP = 0.044 for Riva 2.5 vs 5
P = 0.009 for Riva vs PlaceboP = 0.005 Riva 5 vs PlaceboP = 0.037 for Riva 2.5 vs PlaceboP = 0.44 for Riva 2.5 vs 5
ICH: intracranial hemorrhage
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Apixaban: APPRAISE-2 TrialPrimary Outcome: CV Death, MI, Ischemic Stroke
Apixaban 279 (7.5%)Placebo 293 (7.9%)HR 0.95; 95% CI 0.80-1.11; p=0.509
Alexander JH et al. N Engl J Med. 2011;365:699-708.
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Apixaban: APPRAISE-2 TrialTIMI Major Bleeding
Apixaban 48 (1.3%)Placebo 18 (0.5%) HR 2.59; 95% CI 1.50–4.46; p=0.001
Alexander JH et al. N Engl J Med. 2011;365:699-708.
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No. at riskPlacebo 6471 5844 5468 5121 3794 2291 795Vorapaxar 6473 5897 5570 5199 3881 2318 832
HR (95% CI): 0.92 (0.85, 1.01)P-value= 0.072
Placebo Vorapaxar2-year KM rate 19.9% 18.5%
Tricoci P et al. N Engl J Med. 2012;366:20-33.
TRACER: Vorapaxar in ACS PatientsPrimary Endpoint – CV Death, MI, Stroke, Hospitalization for Ischemia, Urgent Revascularization
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No. at risk
Placebo 6471 5895 5575 5263 3922 2383 830
Vorapaxar 6473 5949 5684 5356 4023 2427 868
HR (95% CI): 0.89 (0.81, 0.98)P-value= 0.018
Placebo Vorapaxar
2-year KM rate 16.4% 14.7%
Tricoci P et al. N Engl J Med. 2012;366:20-33.
TRACER: Vorapaxar in ACS PatientsSecondary Endpoint – CV Death, MI, Stroke
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GUSTO Moderate/Severe
HR (95% CI): 1.35 (1.16, 1.58)P-value <0.001
Placebo Vorapaxar
2-year KM rate 5.2% 7.2%
No. at risk6441 5673 5281 4823 3511 2038 6786446 5694 5272 4760 3411 1965 657
HR (95% CI): 3.39 (1.78, 6.45)P-value <0.001
Tricoci P et al. N Engl J Med. 2012;366:20-33.
Intracerebral Hemorrhage
TRACER: Bleeding Outcomes
Placebo Vorapaxar
2-year KM rate 0.24% 1.07%
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n=156
RR 0.34 (0.10-1.18)P = 0.10
n=157
RR 1.02 (0.41-2.50)P = 0.99
n=148
RR 0.36 (0.11-1.24)P = 0.12
n=461
RR 0.58 (0.25-1.41)P = 0.20
n=142
RR (95% CI) vs. placebo
Placebo Active combined atopaxar 50mg QD 100mg QD 200mg QD
ATOPAXAR in ACS Patients: LANCELOT-ACS Incidence of CV Death, MI, or Stroke
O’Donoghue M et al. Circulation. 2011;123:1843-1853.
5.6%
3.3%
1.9% 2.0%
5.7%
0.0%
2.0%
4.0%
6.0%
8.0%
10.0%
12.0%
P trend = 0.28
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n=153
RR 0.77 (0.38-1.60)P = 0.53
n=156
RR 1.20 (0.63-2.29)P = 0.60
n=146
RR 0.74 (0.35-1.56)P = 0.46
n=455
RR 0.91 (0.52-1.63)P = 0.77
n=138
RR (95% CI) vs. placebo
Placebo Active combined atopaxar 50mg QD 100mg QD 200mg QD
ATOPAXAR in ACS Patients: LANCELOT-ACS Incidence of Any TIMI Bleeding
TIMI minimal
TIMI minor
TIMI major
1.3%2.6%
1.4%0.7%
0.7%
0.7%
1.3%
9.4% 7.3%
7.2%
8.3%
6.2%
0%
2%
4%
6%
8%
10%
12%
14%P trend = 0.63
O’Donoghue M et al. Circulation. 2011;123:1843-1853.
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Acute CoronarySyndromesTreatment of STEMI
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EMS Transport
Onset of symptoms of
STEMI
9-1-1EMS
dispatch
EMS on-scene• Encourage 12-lead ECGs• Consider prehospital fibrinolytic if capable
and EMS-to-needle within 30 min
GOALSPCI
capable
Not PCIcapable
Hospital fibrinolysis: door-to-needle within 30 min
EMS triage plan
Golden hr = 1st 60 min Total ischemic time: within 120 min
Patient EMS Prehospital fibrinolysisEMS-to-needlewithin 30 min
EMS transportEMS-to-balloon within 90 min
Patient self-transport Hospital door-to-balloon within 90 min
Dispatch 1 min
5 min 8 min
Time to Treatment Is Critical in STEMI
Figure adapted with permission from Antman EM et al. J Am Coll Cardiol. 2008;51:210-247.
• Time to reperfusion is a critical determinant of the extent of myocardial damage and clinical outcomes in patients with STEMI
• Key factors in STEMI care are rapid, accurate diagnosis and keeping the encounter time to reperfusion as short as possible
0.4 million discharges per year for STEMI in US
Inter-hospitaltransfer
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Effect of Door-to-Balloon Time on Mortality in Patients with STEMI
Reproduced with permission from McNamara RL et al. J Am Coll Cardiol. 2006;47:2180-2186.
In-hospital mortality and door-to-balloon time; P for trend <0.001
876543210
≤90 >90-120 >120-150 >150
Door-to-Balloon Time (min)
In-h
ospi
tal M
orta
lity,
%
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*P<0.05 for all Bradley EH et al. N Engl J Med. 2006;355:2308-2320.
Door to Balloon (DTB) An Alliance for Quality Campaign
StrategyMean reduction
in door-to-balloon time, min*
Having emergency medicine physicians activate the cath lab 8.2
Having a single call to a central page operator activate the cath lab 13.8
Having the ED activate the cath lab while patient is still en route 15.4
Expecting staff to arrive at the cath lab within 20 minutes after page 19.3
Having an attending cardiologist always on site 14.6
Having staff in the ED and cath lab use and receive real-time feedback 8.6
STRATEGIES ASSOCIATED WITH A SIGNIFICANT REDUCTION IN DTB TIME
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Kushner FG et al. J Am Coll Cardiol. 2009;54:2205-2241.
STEMI patient who is a candidate for reperfusion
Initially seen at a PCI- capable facility
Initially seen at a non–PCI-capable facility
Diagnostic angio
Send to cath lab for primary PCI
(Class I, LOE: A)
At PCI facility,
evaluate for timing of diagnostic
angio
Prep antithrombotic (anticoagulant plus antiplatelet) regimen
Medical therapy only PCI CABG
NOT HIGH RISKTransfer to a PCI facility may be
considered (Class IIb, LOE: C), especially if
ischemic symptoms persist and failure to
reperfuse is suspected
HIGH RISKTransfer to a PCI
facility is reasonable for early diagnostic angio and possible PCI or CABG (Class
IIa, LOE: B), High-risk patients as
defined by 2007 STEMI Focused Update should
undergo cath (Class I, LOE: B)
Initial treatment with fibrinolytic therapy
(Class I, LOE: A)Transfer for primary PCI (Class I, LOE: A) Selection of
reperfusion strategy
2009 ACC/AHA STEMI/PCI Guidelines Focused UpdatePathway: Triage and Transfer for PCI in STEMI
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PCI vs Fibrinolysis Systematic Overview
Short term (4-6 weeks)
Keeley EC et al. Lancet. 2003;361:13-20.
P=0.0002P=0.0003 P<0.0001
P<0.0001
P=0.0004
(23 RCTs, n=7,739)
8.5 7.3 7.2
22.0
2.0
7.24.9
2.8
6.8
1.00.0
5.0
10.0
15.0
20.0
25.0
Death DeathSHOCK
excl.
Reinfarction Recurrentischemia
Stroke
Perc
ent (
%)
LysisPCI
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Medical Therapy for STEMI Managed by Primary PCI
ASA
Anticoagulant UFH (Bival)
Thienopyridine
Clopidogrel 600Prasugrel 60
Beta Blocker IV prn Oral within 24h
GP IIb/IIIaEptifibatideAbciximab
Statin
Presentation Access—Wire—Balloon
EDCCL
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Anti-ischemic Effects VersusBleeding Risk
Acute CoronarySyndromes
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Recent ACS TrialsForging a New Paradigm for Upstream Management
ISCH
EMIA
: The
trad
ition
al, p
rimar
y co
ncer
n of
the
emer
genc
y ph
ysic
ian
BLEEDING: Newer, important concern for the cardiologist: A novel issue for the emergency physician
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Mortality
Major Bleeding
TransfusionHypotension Cessation of ASA/Clopidogrel
Ischemia Stent Thrombosis Inflammation
Bhatt DL et al. In Braunwald: Harrison’s Online 2005.
Possible Relationship BetweenBleeding and Mortality
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CURE: Life-Threatening Bleeding
Life-threatening Bleeding 1.8 2.2 Fatal 0.2 0.2 Causing 5 g/dL drop hemoglobin 0.9 0.9 Hypotension requiring inotropic therapy 0.5 0.5 Surgery required 0.7 0.7 Causing hemorrhagic stroke 0.1 0.1 Transfusion of ≥ 4 blood units 1.0 1.2Transfusion of ≥ 2 blood units 2.2 2.8
Placebo + ASA*n = 6303
(%)
Clopidogrel + ASA*n = 6259
(%)
* In combination with standard therapyThe CURE Trial Investigators. N Engl J Med. 2001;345:494-502.
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TRITON TIMI 38 Bleeding Events – Safety Cohort (n=13,457)
% E
vent
s
ARD 0.6%HR 1.32P=0.03
NNH=167
ARD 0.5%HR 1.52P=0.01
ARD 0.2%P=0.23
ARD 0%P=0.74
ARD 0.3%P=0.002
Clop 0 (0) % Pras 6 (2.3)% (P=0.02)
Wiviott SD et al. N Engl J Med. 2007;357:2001-2015.
LifeThreatening
TIMI MajorBleeds
ClopidogrelPrasugrel
0.9
2.4
1.4
0
2
4ICH in patients with prior stroke/TIA (n=518)
0.91.1
0.10.4 0.3 0.3
Nonfatal Fatal ICH
1.8
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PLATO Major Bleeding: Non-CABG vs CABG
Kapl
an-M
eier
est
imat
ed ra
te (
%)
Wallentin L et al. N Engl J Med. 2009;361:1045-1057.
P=0.026
P=0.025
NS
NS
Non-CABGPLATO major
bleeding
8
7
6
5
4
3
2
1
0 Non-CABGTIMI major bleeding
CABGPLATO major
bleeding
CABG TIMI major bleeding
4.5
3.8
2.8
2.2
7.47.9
5.35.8
TicagrelorClopidogrel
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Quality Outcomes in ACS
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Mean 30-day Hospital Readmission Rates Following PCI: By Hospital Decile of Readmission
Curtis JP et al. J Am Coll Cardiol. 2009;54:903-907.
Perc
ent R
eadm
issi
on
0
15
20
25
30
5
10
Hospital Decile of Readmission Rate
1st 2nd 3rd 6th 7th 8th 9th 10th 4th 5th
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HospitalsQuality of Care for Heart Attack
Data: IPRO analysis of data from CMS Hospital Compare.
Percent of patients who received recommended care Heart attack 30-day mortality
Source: Commonwealth Fund National Scorecard on US Health System Performance, 2011.
0
25
50
75
100100 98
94
10th %ile(best)
Median 90th %ile(worst)
Perc
ent
Heart attack 30-day mortality
Series10
5
10
15
20
1415
1617
18
10th %ile 25th %ile Median 75th %ile 90th %ile(best) (worst)
Perc
ent
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OPTIMAL MANAGEMENT OF ACS PATIENTSReducing Risk of Hospital Readmissions
• Selection of antiplatelet medications should be made based on the following patient-specific considerations
– Risk of major adverse ischemic events
– Risk of bleeding complications
– Likelihood of poor adherence to prescribed medications
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CONCLUSIONS Key Considerations for Clinical Management of ACS
• Need for differential diagnosis of the spectrum of ACS• Fundamental aspects of management of acute chest pain
– Elements for optimal early hospital care• The importance of risk stratification to guide practice decisions
– Options: initial conservative or invasive strategy – If invasive strategy, rationale for early catheterization
• The expanded field of existing antiplatelet treatment options– Clopidogrel, prasugrel, ticagrelor
• Emerging antiplatelet/anticoagulant therapies for ACS– Strong contender: very low dose rivaroxaban
• Standards of treatment for STEMI• The need to balance anti-ischemic effects versus bleeding risk• The growing importance of quality outcomes in ACS
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Question and Answer Session
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Thank you for joining us today.Please remember to turn in your evaluation form.
Your participation will help shape futureCME activities.
Please visit www.rockpointe.com for an enduring archive of this program in Spring 2012, and additional
educational materials on ACS.
Acute Coronary SyndromesFrom the Emergency Department to the
Coronary Care Unit to the Office