Transcript P - Rockpointe

Acute Coronary Syndromes
From 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:
TO BE FILLED IN BY PRESENTING
PHYSICIAN
• Presenting Physician,
MD
Category – Disclosures
Steering Committee Disclosures
The Steering Committee reported the following relevant
financial relationships that they or their spouse/partner have
with 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
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
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
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
Chest Pain Case
Chest Pain Case
Initial 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
Chest Pain Case
Initial ECG
Chest Pain Case
Treatment 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?
•
Chest Pain Case
Initial 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?
Acute Coronary
Syndromes
Clinical Spectrum and Presentation
Acute Coronary Syndromes
Scope 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-e209
Lloyd-Jones D et al. Circulation. 2010;121:e46-e215.
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
Mortality in Acute Coronary Syndromes
Death from Hospital Admission to 6 Months
% Mortality
16
12
STEMI
8
NSTEMI
UA
4
0
0
30
60
90
120
150
180
Days
Fox KA et al. BMJ. 2006;333:1091.
GRACE n=43,810
Risk Stratification and Early
Hospital Care
Management of Acute Chest Pain Syndrome
Role 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
Acute Coronary Syndromes
Risk Stratification
Chest Pain Syndrome Suggestive of Ischemia
Immediate Assessment within 10 Minutes
Initial Labs
and Tests
Emergent
Care
• 12 lead ECG
• IV access
• Obtain initial
cardiac enzymes
• Cardiac
monitoring
• Electrolytes, CBC
lipids, BUN/
creatinine,
glucose, coags
• Oxygen
• Chest x-ray
• Aspirin
• Nitrates
History &
Physical
• Establish
diagnosis
• Read ECG
• Identify
complications
• Assess for
reperfusion
“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
TIMI RISK SCORE for UA/NSTEMI
Risk 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
PRESENTATION
Recent (≤ 24H) severe angina
↑ cardiac markers
ST deviation ≥ 0.5 mm
RISK SCORE = Total Points (0-7)
Antman EM et al. JAMA. 2000;284:835-842.
RISK OF CARDIAC EVENTS (%)
BY 14 DAYS IN TIMI 11B
RISK
SCORE
DEATH
OR MI
DEATH, MI, OR
URGENT REVASC
0/1
2
3
4
5
6/7
3
3
5
7
12
19
5
8
13
20
26
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)
Anterior ST Segment Depression
Classifications
Anterior ST-segment depression
TIMI flow grade 2/3
in culprit artery
TIMI flow grade 0/1
in culprit artery
- Troponin
+ Troponin
+ Troponin
Unstable
angina
NSTEMI
STEMI
Gibson CM et al. 2008 AHA Scientific Sessions
Troponin Levels Predict Risk of
Mortality in UA/NSTEMI
7.5 %
Mortality at 42 days; % of patients
8
7
6.0 %
6
5
4
3
2
1
0
1.0 %
831
0 to <0.4
3.4 %
3.7 %
148
134
1.7 %
174
50
0.4 to <1.0 1.0 to <2.0 2.0 to <5.0 5.0 to <9.0
Cardiac troponin I (ng/mL)
Antman EM et al. N Engl J Med. 1996;335:1342-1949.
67
≥ 9.0
Acute Coronary
Syndromes
Early Hospital Care
Optimal Upstream Management of
Ischemic 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
Treatment of Acute Coronary Syndrome
Early Invasive
Braunwald E et al. Available at: www.acc.org.
Bowen WE, McKay RG. N Engl J Med. 2001;344:1939-1942.
Initial
Conservative
* Also known as Q-wave MI
† Also known as non-Q-wave MI
Current Medical Management of
Unstable Angina and NSTEMI
Acute Therapy
Maintenance Therapy
• Oxygen, Bed Rest
• Antiplatelet Therapy
• ECG Monitoring
• Beta Blockers
• Nitroglycerin
• Calcium Channel Blockers
• Beta Blockers
• Lipid-lowering Agents
• ACE Inhibitors
• ACE Inhibitors
• Antiplatelet Therapy
• Oral Anticoagulant Therapy
• Anticoagulant Therapy
Braunwald E et al. Available at: www.acc.org.
Acute Coronary
Syndrome
Procedural Considerations:
Initial Conservative or Invasive Strategy –
Based on Risk Assessment
Conservative Therapy Option for UA/NSTEMI
Early 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
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 inhibitor
Anderson JL et al. Circulation. 2007;116:e148-e304
ACCF/AHA Guidelines 2011 Focused Update
Early Invasive Strategies
I
IIa
IIb
III
High-risk patients with:
- Refractory ischemia
-
Wright RS et al. Circulation. 2011;123:2022-2060
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
TACTICS: Primary Endpoint
Death, MI, Rehospitalized for ACS at 6 Months
19.4%
20
15.9%
% Patients
16
12
O.R 0.78
95% CI (0.62, 0.97)
P=0.025
8
4
Conservative:
Invasive:
0
0
1
2
Cannon CP et al. N Engl J Med. 2001;344:1879-1887.
3
4
Time (months)
5
6
Updated Meta-analysis: Mortality
Study
Deaths, n
Invasive
FRISC-II
45
67
24
TRUCS
3
9
12
TIMI-18
37
39
6
VINO
2
9
6
RITA-3
102
132
60
ISAR-COOL
0
3
1
ICTUS
15
15
12
Overall RR (95% CI)
0.75 (0.63-0.90)
0.1
Favors
Early Invasive
Therapy
Bavry, AA et al. J Am Coll Cardiol. 2006;48:1319-1325.
1
10
Favors
Conservative
Therapy
Follow-up
Conservative Months
Invasive Strategy
Rationale for Early
Catheterization
TIMACS
Rates of death, MI, or stroke within 6 months according to GRACE
risk level and HR (95% CI), early versus delayed invasive strategy
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
*Low/intermediate risk=GRACE score <140
High risk=GRACE score ≥140
Mehta SR et al. N Engl J Med. 2009;310:2165-2175
CRUSADE Registry
Mortality Rates by Early Catheterization
% In-hospital Mortality
10
8
Early Catheterization
8.6
No Early Catheterization
6
3.9
4
2
0.7
0
2.5
2.3
Low
(n=4326)
1.1
Moderate
(n=4492)
High
(n=9108)
Modified PURSUIT Risk Category
Bhatt DL et al. JAMA. 2004;292:2096-2104..
Antithrombotic
Therapy in ACS
Evolving Antiplatelet Therapies
CURE Study
Primary End Point: MI/Stroke/CV Death
Cumulative Hazard Rate
0.14
20%
Relative
Risk
Reduction
Placebo
+ Aspirin
(n=6303)
0.12
0.10
0.08
Clopidogrel
+ Aspirin
(n=6259)
0.06
0.04
P<0.001
n=12,562
0.02
0.00
0
3
6
Months of Follow-up
Yusuf S et al. N Engl J Med. 2001;345:494-502.
9
12
CREDO
Combined endpoint occurrence (%)
Long-Term (1 Year) Benefits of Clopidogrel in PCI Patients
MI, stroke, or death – ITT population
15
Placebo*
Clopidogrel*
11.5%
27% RRR
10
P=0.02
8.5%
5
0
0
3
6
9
Months from randomization
* Plus ASA and other standard therapies
Steinhubl S et al. JAMA. 2002;288:2411-2420.
12
Primary Endpoint (MI/Stroke/CV Death) in
Patients with Previous MI, IS, or PAD*
Primary Outcome Event Rate (%)
CHARISMA: “CAPRIE-like Cohort”
10
n=9,478
8.8%
Placebo + ASA
Clopidogrel + ASA
8
7.3%
6
4
RRR: 17.1 % (95% CI: 4.4%, 28.1%)
P=0.01
2
0
0
* Post hoc analysis
6
12
18
24
Months Since Randomization
Bhatt DL et al. J Am Coll Cardiol. 2007;49:1982-1988.
30
TRITON – TIMI 38
CV Death, MI, Stroke
15
Primary Endpoint (%)
Clopidogrel
12.1
(781)
9.9
(643)
10
Prasugrel
HR 0.80
P=0.0003
5
0
HR 0.81
(0.73-0.90)
P=0.0004
NNT= 46
HR 0.77
P=0.0001
ITT= 13,608
0
30 60 90
Wiviott SD et al. N Engl J Med. 2007;357:2001-2005.
180
270
Days
LTFU = 14 (0.1%)
360
450
PLATO: Kaplan-Meier Estimate of Time to First Primary
Cumulative incidence (%)
Efficacy Event (Composite of CV Death, MI or Stroke)
13
12
11
10
9
8
7
6
5
4
3
2
1
0
9.8
Ticagrelor
HR = hazard ratio
CI = confidence interval
HR 0.84 (95% CI 0.77–0.92), p=0.0003
0
No. at risk
Ticagrelor
Clopidogrel
11.7
Clopidogrel
60
120
180
240
300
360
5,161
5,096
4,147
4,047
Days after randomisation
9,333
9,291
8,628
8,521
Wallentin L et al. N Engl J Med. 2009;361:1045-1057
8,460
8,362
8,219
8,124
6,743
6,743
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
Antithrombotic
Therapy in ACS
Emerging Therapies
Key Investigational Antithrombotic Drugs
• Factor Xa inhibitors
– Rivaroxaban
– Apixaban
• PAR-1 thrombin inhibitors
– Vorapaxar
– Atopaxar
RIVAROXABAN: ATLAS ACS 2 TIMI 51
Primary Efficacy Endpoint: CV Death / MI / Stroke
12
2 Yr KM Estimate
Placebo
10.7%
10
8.9%
8
6
HR 0.84 (0.740.96)
Rivaroxaban
mITT p = 0.008
ITT p = 0.002
(both doses 2.5
mg bid and 5 mg bid)
4
2
0
ARR 1.8%
NNT = 56
0
4
12
16
20
24
1079
2084
421
831
Months After Randomization
No. at Risk
Placebo
Rivaroxaban
8
5113
10229
4307
8502
Mega JL et al. N Engl J Med. 2012;366:9-19.
3470
6753
2664
5137
1831
3554
RIVAROXABAN: ATLAS ACS 2 TIMI 51
Efficacy Endpoints: Very Low Dose 2.5 mg BID
Patients Treated with Aspirin + Thienopyridine
CV Death / MI / Stroke
Cardiovascular Death
5%
HR 0.84
12%
Placebo
HR 0.66
9.0%
mITT
p<0.001
Placebo
4.2%
10.4%
Estimated Cumulative incidence (%)
mITT
p=0.04
ITT
p=0.01
ITT
p<0.001
2.5%
Rivaroxaban
2.5 mg BID
Rivaroxaban
2.5 mg BID
NNT = 59
NNT = 71
0
12
Months
24
Mega JL et al. N Engl J Med. 2012;366:9-19.
0
12
Months
24
RIVAROXABAN: ATLAS ACS 2 TIMI 51
Treatment Emergent Fatal Bleeds and ICH
1.2
1
P = NS for Riva vs Placebo
P = NS for Riva 5 vs Placebo
P = NS for Riva 2.5 vs Placebo
P = 0.044 for Riva 2.5 vs 5
P = 0.009 for Riva vs Placebo
P = 0.005 Riva 5 vs Placebo
P = 0.037 for Riva 2.5 vs Placebo
P = 0.44 for Riva 2.5 vs 5
0.8
Placebo
2.5 mg Rivaroxaban
5.0 mg Rivaroxaban
0.7
P = NS for all
comparisons
0.6
0.4
0.4
0.2
0
0.2
0.4
0.2
0.2
0.1
n=9
n=6 n=15
n=5 n=14 n=18
Fatal
ICH
ICH: intracranial hemorrhage
Adapted from Mega JL et al. N Engl J Med. 2012:336:9-19.
0.1
0.1
n=4
n=5
Fatal ICH
n=8
Apixaban: APPRAISE-2 Trial
Primary 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.
Apixaban: APPRAISE-2 Trial
TIMI 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.
TRACER: Vorapaxar in ACS Patients
Primary Endpoint – CV Death, MI, Stroke, Hospitalization for Ischemia, Urgent Revascularization
2-year KM rate
Placebo
Vorapaxar
19.9%
18.5%
HR (95% CI): 0.92 (0.85, 1.01)
P-value= 0.072
No. at risk
Placebo
Vorapaxar
6471 5844
6473 5897
5468
5570
Tricoci P et al. N Engl J Med. 2012;366:20-33.
5121
5199
3794
3881
2291
2318
795
832
TRACER: Vorapaxar in ACS Patients
Secondary Endpoint – CV Death, MI, Stroke
2-year KM rate
Placebo
Vorapaxar
16.4%
14.7%
HR (95% CI): 0.89 (0.81, 0.98)
P-value= 0.018
No. at risk
Placebo
6471 5895
5575
5263
3922
2383
830
Vorapaxar
6473 5949
5684
5356
4023
2427
868
Tricoci P et al. N Engl J Med. 2012;366:20-33.
TRACER: Bleeding Outcomes
GUSTO Moderate/Severe
2-year KM rate
Placebo
Vorapaxar
5.2%
7.2%
Intracerebral Hemorrhage
2-year KM rate
Placebo
Vorapaxar
0.24%
1.07%
HR (95% CI): 3.39 (1.78, 6.45)
P-value <0.001
HR (95% CI): 1.35 (1.16, 1.58)
P-value <0.001
No. at risk
6441 5673 5281 4823
6446 5694 5272 4760
Tricoci P et al. N Engl J Med. 2012;366:20-33.
3511
3411
2038
1965
678
657
ATOPAXAR in ACS Patients: LANCELOT-ACS
Incidence of CV Death, MI, or Stroke
12.0%
P trend = 0.28
10.0%
8.0%
6.0%
5.7%
5.6%
4.0%
3.3%
0.0%
2.0%
1.9%
2.0%
Placebo
Active combined atopaxar
50mg QD
100mg QD
200mg QD
n=142
n=461
n=156
n=157
n=148
RR (95% CI)
vs. placebo
RR 0.58 (0.25-1.41)
P = 0.20
RR 0.34 (0.10-1.18)
P = 0.10
RR 1.02 (0.41-2.50)
P = 0.99
RR 0.36 (0.11-1.24)
P = 0.12
O’Donoghue M et al. Circulation. 2011;123:1843-1853.
ATOPAXAR in ACS Patients: LANCELOT-ACS
Incidence of Any TIMI Bleeding
14%
TIMI minimal
P trend = 0.63
12%
TIMI minor
10%
TIMI major
8%
8.3%
6%
4%
9.4%
7.2%
2%
0%
7.3%
0.7%
0.7%
Placebo
1.3%
Active combined atopaxar
1.3%
2.6%
0.7%
6.2%
1.4%
50mg QD
100mg QD
200mg QD
n=138
n=455
n=153
n=156
n=146
RR (95% CI)
vs. placebo
RR 0.91 (0.52-1.63)
P = 0.77
RR 0.77 (0.38-1.60)
P = 0.53
RR 1.20 (0.63-2.29)
P = 0.60
RR 0.74 (0.35-1.56)
P = 0.46
O’Donoghue M et al. Circulation. 2011;123:1843-1853.
Acute Coronary
Syndromes
Treatment of STEMI
Time to Treatment Is Critical in STEMI
0.4 million discharges per year for STEMI in US
Hospital fibrinolysis:
door-to-needle within 30 min
Not PCI
capable
Onset of
symptoms of
STEMI
9-1-1
EMS
dispatch
EMS on-scene
PCI
capable
GOALS
5 min 8 min EMS Transport
Patient EMS Prehospital fibrinolysis
Dispatch 1 min
Inter-hospital
transfer
• Encourage 12-lead ECGs
• Consider prehospital fibrinolytic if capable
and EMS-to-needle within 30 min
EMS-to-needle
within 30 min
Golden hr = 1st 60 min
EMS transport
EMS-to-balloon within 90 min
Patient self-transport
Hospital door-to-balloon within 90 min
Total ischemic time: within 120 min
• 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
Figure adapted with permission from Antman EM et al. J Am Coll Cardiol. 2008;51:210-247.
Effect of Door-to-Balloon Time on
Mortality in Patients with STEMI
8
In-hospital Mortality, %
7
6
5
4
3
2
1
0
≤90
>90-120
>120-150
Door-to-Balloon Time (min)
In-hospital mortality and door-to-balloon time; P for trend <0.001
Reproduced with permission from McNamara RL et al. J Am Coll Cardiol. 2006;47:2180-2186.
>150
Door to Balloon (DTB)
An Alliance for Quality Campaign
STRATEGIES ASSOCIATED WITH A SIGNIFICANT REDUCTION IN DTB TIME
Strategy
Mean 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
*P<0.05
for all
Bradley EH et al. N Engl J Med. 2006;355:2308-2320.
2009 ACC/AHA STEMI/PCI Guidelines Focused Update
Pathway: Triage and Transfer for PCI in STEMI
STEMI patient who is a
candidate for reperfusion
Initially seen at a non–
PCI-capable facility
Initially seen at a PCIcapable facility
Send to cath lab for
primary PCI
(Class I, LOE: A)
Transfer for primary PCI
(Class I, LOE: A)
Prep antithrombotic (anticoagulant plus
antiplatelet) regimen
Diagnostic angio
Medical therapy
only
PCI
CABG
Kushner FG et al. J Am Coll Cardiol. 2009;54:2205-2241.
At PCI
facility,
evaluate
for timing of
diagnostic
angio
Initial treatment with
fibrinolytic therapy
Selection of
reperfusion strategy
HIGH RISK
Transfer 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)
(Class I, LOE: A)
NOT HIGH RISK
Transfer to a PCI
facility may be
considered (Class
IIb, LOE: C),
especially if
ischemic symptoms
persist and failure to
reperfuse is
suspected
PCI vs Fibrinolysis
Systematic Overview
Short term (4-6 weeks)
(23 RCTs, n=7,739)
25.0
Percent (%)
20.0
15.0
10.0
22.0
Lysis
PCI
P=0.0002
8.5
7.2
5.0
P=0.0003
P<0.0001
7.3
7.2
4.9
P<0.0001
6.8
2.8
P=0.0004
2.0 1.0
0.0
Death
Keeley EC et al. Lancet. 2003;361:13-20.
Death
SHOCK
excl.
Reinfarction
Recurrent
ischemia
Stroke
Medical Therapy for STEMI Managed by
Primary PCI
ED
CCL
Presentation
Access—Wire—Balloon
ASA
Anticoagulant
Thienopyridine
UFH
Clopidogrel 600
Prasugrel 60
Eptifibatide
Abciximab
GP IIb/IIIa
Beta Blocker
Statin
(Bival)
IV prn
Oral within 24h
Acute Coronary
Syndromes
Anti-ischemic Effects Versus
Bleeding Risk
Recent ACS Trials
ISCHEMIA: The traditional, primary
concern of the emergency physician
Forging a New Paradigm for Upstream Management
BLEEDING: Newer, important concern for the cardiologist:
A novel issue for the emergency physician
Possible Relationship Between
Bleeding and Mortality
Major Bleeding
Hypotension
Cessation of
ASA/Clopidogrel
Transfusion
Ischemia
Stent Thrombosis
Inflammation
Mortality
Bhatt DL et al. In Braunwald: Harrison’s Online 2005.
CURE: Life-Threatening Bleeding
Life-threatening Bleeding
Fatal
Causing 5 g/dL drop hemoglobin
Hypotension requiring inotropic therapy
Surgery required
Causing hemorrhagic stroke
Transfusion of ≥ 4 blood units
Transfusion of ≥ 2 blood units
* In combination with standard therapy
The CURE Trial Investigators. N Engl J Med. 2001;345:494-502.
Placebo + ASA*
n = 6303
(%)
Clopidogrel + ASA*
n = 6259
(%)
1.8
0.2
0.9
0.5
0.7
0.1
1.0
2.2
2.2
0.2
0.9
0.5
0.7
0.1
1.2
2.8
TRITON TIMI 38
Bleeding Events – Safety Cohort (n=13,457)
% Events
4
ICH in patients with
prior stroke/TIA
(n=518) Clop 0 (0) %
Pras 6 (2.3)%
(P=0.02)
Clopidogrel
Prasugrel
2.4
2
1.8
1.4
0.9
0.9
1.1
0.4
0
0.1
0.3
0.3
TIMI Major
Bleeds
Life
Threatening
Nonfatal
Fatal
ICH
ARD 0.6%
HR 1.32
P=0.03
NNH=167
ARD 0.5%
HR 1.52
P=0.01
ARD 0.2%
P=0.23
ARD 0.3%
P=0.002
ARD 0%
P=0.74
Wiviott SD et al. N Engl J Med. 2007;357:2001-2015.
PLATO
Major Bleeding: Non-CABG vs CABG
Kaplan-Meier estimated rate (%)
NS
Ticagrelor
Clopidogrel
8
7.9
7.4
7
NS
5.8
6
5
4
5.3
P=0.026
4.5
3.8
P=0.025
2.8
3
2.2
2
1
0
Non-CABG
PLATO major
bleeding
Non-CABG
TIMI major
bleeding
Wallentin L et al. N Engl J Med. 2009;361:1045-1057.
CABG
PLATO major
bleeding
CABG
TIMI major
bleeding
Quality Outcomes in ACS
Mean 30-day Hospital Readmission Rates
Following PCI: By Hospital Decile of Readmission
Percent Readmission
30
25
20
15
10
5
0
1st
2nd
3rd
4th
5th
6th
7th
Hospital Decile of Readmission Rate
Curtis JP et al. J Am Coll Cardiol. 2009;54:903-907.
8th
9th
10th
Hospitals
Quality of Care for Heart Attack
Percent of patients who received recommended care
Heart attack 30-day mortality
100
100
98
Heart attack 30-day mortality
94
10th %ile
(best)
Median
20
15
50
Percent
Percent
75
25th %ile
25
14
15
10
5
0
0
10th %ile
(best)
Median 90th %ile
(worst)
Data: IPRO analysis of data from CMS Hospital Compare.
Source: Commonwealth Fund National Scorecard on US Health System Performance, 2011.
16
75th %ile
17
90th %ile
(worst)
18
OPTIMAL MANAGEMENT OF ACS PATIENTS
Reducing 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
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
Question and
Answer Session
Acute Coronary Syndromes
From the Emergency Department to the
Coronary Care Unit to the Office
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