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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

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

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

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 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

Chest Pain CaseInitial ECG

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?

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?

Acute Coronary Syndromes

Clinical Spectrum and Presentation

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.

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 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

Risk Stratification and Early Hospital Care

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

Acute Coronary SyndromesRisk Stratification

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

“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

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

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

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 )

Acute CoronarySyndromesEarly Hospital Care

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

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

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.

Acute Coronary Syndrome

Procedural Considerations:Initial Conservative or Invasive Strategy –

Based on Risk Assessment

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

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

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

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.

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)

Invasive StrategyRationale for Early

Catheterization

*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

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

Antithrombotic Therapy in ACS

Evolving Antiplatelet Therapies

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

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

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%

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

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

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 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

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.

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

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.

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.

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

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

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%

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

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.

Acute CoronarySyndromesTreatment of STEMI

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

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,

%

*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

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

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

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

Anti-ischemic Effects VersusBleeding Risk

Acute CoronarySyndromes

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

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

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.

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

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

Quality Outcomes in ACS

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

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

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

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

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