stemi-wrap on evidence-based management of stemi: the emergency department perspective charles v....

STEMI-WRAP on Evidence-Based Management of STEMI:

The Emergency Department Perspective

STEMI-WRAP on Evidence-Based Management of STEMI:

The Emergency Department Perspective

Charles V. Pollack, Jr., M.A., M.D., FACEP, FAHA

Professor and Chair, Emergency Medicine, Pennsylvania Hospital

University of Pennsylvania Health System

Philadelphia

Charles V. Pollack, Jr., M.A., M.D., FACEP, FAHA

Professor and Chair, Emergency Medicine, Pennsylvania Hospital

University of Pennsylvania Health System

Philadelphia

STEMISTEMI

Accounts for 15-20% of cases of ACS seen in ED; UA/NSTEMI (collectively, NSTE ACS) account for majority

High-visibility diagnosis because of its high morbidity and mortality, patient and family fears and expectations, and intensity of monitoring by observers inside and outside the hospital—QI, payors, JCAHO, P4P

Accounts for 15-20% of cases of ACS seen in ED; UA/NSTEMI (collectively, NSTE ACS) account for majority

High-visibility diagnosis because of its high morbidity and mortality, patient and family fears and expectations, and intensity of monitoring by observers inside and outside the hospital—QI, payors, JCAHO, P4P

STEMISTEMI

Pathophys: STEMI is caused by complete obstruction of an epicardial vessel, which causes angina or anginal equivalent and diagnostic ECG changes of ST-segment elevation

Recognition of STEMI, which by GLs should occur within 10 minutes of ED arrival, launches the ED-cardiology team on a fast-moving track that demands prompt stabilization, evidence-based medical management, and quick decisions regarding reperfusion therapy

Dx of STEMI is clinical + electrocardiographic and DOES NOT require assessment of cardiac markers

Pathophys: STEMI is caused by complete obstruction of an epicardial vessel, which causes angina or anginal equivalent and diagnostic ECG changes of ST-segment elevation

Recognition of STEMI, which by GLs should occur within 10 minutes of ED arrival, launches the ED-cardiology team on a fast-moving track that demands prompt stabilization, evidence-based medical management, and quick decisions regarding reperfusion therapy

Dx of STEMI is clinical + electrocardiographic and DOES NOT require assessment of cardiac markers

STEMISTEMI

STEMI typically result from fissure or frank rupture of an atherosclerotic plaque Stimulates local activation of:

• platelets• coagulation cascade• complement

Platelet aggregate forms over site of plaque injury and as it matures (fibrinogen→fibrin) causes complete obstruction of distal flow. To the extent that collateral flow downstream is lacking, ischemia quickly ensues and infarction starts to occur within minutes

STEMI typically result from fissure or frank rupture of an atherosclerotic plaque Stimulates local activation of:

• platelets• coagulation cascade• complement

Platelet aggregate forms over site of plaque injury and as it matures (fibrinogen→fibrin) causes complete obstruction of distal flow. To the extent that collateral flow downstream is lacking, ischemia quickly ensues and infarction starts to occur within minutes

STEMISTEMI

Pharmacologic therapy in STEMI is therefore directed at this triad of abnormal activity: Platelet activation—anti-activation and anti-

aggregation• ASA and clopidogrel• GPIs

Coagulation activation—anticoagulants Complement activation—anti-inflammatories . . . ?

Statins In preparation for reperfusion therapy by lysis or

angiography and primary PCI

Pharmacologic therapy in STEMI is therefore directed at this triad of abnormal activity: Platelet activation—anti-activation and anti-

aggregation• ASA and clopidogrel• GPIs

Coagulation activation—anticoagulants Complement activation—anti-inflammatories . . . ?

Statins In preparation for reperfusion therapy by lysis or

angiography and primary PCI

Guidelines for STEMI diagnosis and managementGuidelines for STEMI diagnosis and management

complex disease state with broad ranges of presentation and a multitude of therapeutic options

Many important and pertinent clinical studies

Information overload!

Need evidence-based guidelines to promote consistency of care and resulting better outcomes

complex disease state with broad ranges of presentation and a multitude of therapeutic options

Many important and pertinent clinical studies

Information overload!

Need evidence-based guidelines to promote consistency of care and resulting better outcomes

Guidelines for STEMI managementGuidelines for STEMI management

ACC/AHA Joint Task Force: 1990, 1996, 1999

Last comprehensive update in 2004 Widely read, lots of interest Clear evidence scoring, sensible recommendations,

temporal sequencing• “soup to nuts”

Recapitulation, interpretation, and promulgation for upstream providers in Annals of Emergency Medicine

ACC/AHA Joint Task Force: 1990, 1996, 1999

Last comprehensive update in 2004 Widely read, lots of interest Clear evidence scoring, sensible recommendations,

temporal sequencing• “soup to nuts”

Recapitulation, interpretation, and promulgation for upstream providers in Annals of Emergency Medicine

Guidelines for STEMI managementGuidelines for STEMI management

ACC/AHA Joint Task Force: presented “focused update” in December 2007 “focus” (from upstream perspective) on reperfusion

strategies and opportunities to minimize delays to reperfusion

Beta blockers Choices of anticoagulants New recommendations regarding clopidogrel

ACC/AHA Joint Task Force: presented “focused update” in December 2007 “focus” (from upstream perspective) on reperfusion

strategies and opportunities to minimize delays to reperfusion

Beta blockers Choices of anticoagulants New recommendations regarding clopidogrel

Class I Benefit >>> Risk

Procedure/ Treatment SHOULD be performed/ administered

Class IIa Benefit >> RiskAdditional studies with focused objectives needed

IT IS REASONABLE to perform procedure/administer treatment

Class IIb Benefit ≥ RiskAdditional studies with broad objectives needed; Additional registry data would be helpful

Procedure/Treatment MAY BE CONSIDERED

Class III Risk ≥ BenefitNo additional studies needed

Procedure/Treatment should NOT be per-formed/administered SINCE IT IS NOT HELPFUL AND MAY BE HARMFUL

shouldis recommendedis indicatedis useful/effective/

beneficial

is reasonablecan be useful/effective/

beneficialis probably recommended

or indicated

may/might be consideredmay/might be reasonableusefulness/effectiveness is

unknown /unclear/uncertain or not well established

is not recommendedis not indicatedshould notis not useful/effective/

beneficialmay be harmful

Applying Classification of Recommendations

“The Guidelines”Weighing the Evidence

“The Guidelines”Weighing the Evidence

Weight of evidence grades:= Data from many large, randomized trials= Data from fewer, smaller randomized trials, careful

analyses of nonrandomized studies, observational registries

= Expert consensus

Weight of evidence grades:= Data from many large, randomized trials= Data from fewer, smaller randomized trials, careful

analyses of nonrandomized studies, observational registries

= Expert consensus

Time Delays and 30 Day Outcome in STEMI Time Delays and 30 Day Outcome in STEMI

Collins. Collins. NEJMNEJM. 1997;336:847.. 1997;336:847.

45,000 patients in 45,000 patients in placebo controlled placebo controlled

lytic trials.lytic trials.

00

2020

3030

66 1212 1818 2424

4040

00

1010

Hours from onset of symptomsHours from onset of symptomsto randomizationto randomization

30003000

Loss of benefitLoss of benefitper hour of delayper hour of delay1.61.6±0.6 lives per±0.6 lives per

1000 patients1000 patients

Liv

es s

aved

/100

0 p

atie

nts

Liv

es s

aved

/100

0 p

atie

nts

14,00014,000

12,00012,000

90009000

70007000

Time Delays and 30 Day Outcome in STEMI: Primary PCI (NRMI-2)

Time Delays and 30 Day Outcome in STEMI: Primary PCI (NRMI-2)

Cannon C, et al. JAMA 2000;283:2941-2947

Prehospital IssuesPrehospital Issues EMS

Emphasis on early defibrillation; AEDs; 911 dispatchers training & use of national protocols; 12-lead ECGs

Chest Pain Evaluation & Treatment Emphasis on giving chewable ASA, unless contraindicated &

prehospital ECG & checklist

Prehospital Fibrinolysis Upgraded to a Class IIa (Level B) Recommendation

• although not particularly likely in most systems

Prehospital Destination Protocols Where to transport STEMI patients: a plan must be in place Special considerations

• Cardiogenic Shock • Fibrinolytic contraindicated

EMS Emphasis on early defibrillation; AEDs; 911 dispatchers

training & use of national protocols; 12-lead ECGs

Chest Pain Evaluation & Treatment Emphasis on giving chewable ASA, unless contraindicated &

prehospital ECG & checklist

Prehospital Fibrinolysis Upgraded to a Class IIa (Level B) Recommendation

• although not particularly likely in most systems

Prehospital Destination Protocols Where to transport STEMI patients: a plan must be in place Special considerations

• Cardiogenic Shock • Fibrinolytic contraindicated

Patients Transported by EMS After Calling 9-1-1

Onset of STEMI

Symptoms

Cal

l 911

Cal

l Fas

t

9-1-1 EMS

Dispatch

EMS on-scene• Encourage 12-lead ECG

• Consider prehospital fibrinolytic if capable and EMS-to-needle < 30

min

EM

S T

riag

e P

lan

Not PCICapableHospital

PCICapableHospital

Interhospital

TransferHospital Fibrinolysis:Door-to-needle within<30 min

EMS transport:EMS to Balloon within 90 min

Patient self-transport: Hospital Door-to-Balloon within 90 min

EMS transportEMS on

scene Within 8 min

Dispatch

1 min

Patient

5’ aftersx onset

Goals

Total ischemic time: Within 120 min*

PPCI:Door-to-balloon within<90 min

PPCI:Door-to-balloon within<90 min

ACC/AHA 2007 STEMI Focused Update: Acute Medical Therapy

General treatment measures

Aspirin, nitrates, oxygen, analgesicsa (morphine)

Infarct size limitation β-blockers (not for acute use in patients with evidence of heart failure)

Reperfusion Thrombolysis (within 30 min) or primary PCI (within 90 min)

Anticoagulant and antiplatelet therapy

UFH or enoxaparin or fondaparinuxb

Clopidogrel 75 mg/d added to aspirin for patients undergoing fibrinolysis; 300 mg loading dose for patients <75 y who receive fibrinolytic therapy or who do not receive reperfusion therapy If PCI: clopidogrel, GP IIb/IIIa inhibitors

a Patients routinely taking NSAIDs (except for aspirin), both nonselective as well as COX-2 selective agents, before STEMI should have those agents discontinued at the time of presentation with STEMI because of the increased risk of mortality, reinfarction, hypertension, heart failure, and myocardial rupture associated with their use.

b Because of the risk of catheter thrombosis, fondaparinux should not be used as the sole anticoagulant to support PCI. An additional anticoagulant with anti-IIa activity should be administered.

Antman E, et al. J Am Coll Cardiol. doi:10.1016/j.jacc.2007.10.001.

Class I Modified Recommendations

Reperfusion Therapy for STEMI

STEMI patients presenting to a hospital with PCI capability should be treated with primary PCI within 90 minutes of first medical contact as a systems goal (Level of Evidence: A)

STEMI patients presenting to a hospital without PCI capability and who cannot be transferred to a PCI center and undergo PCI within 90 minutes of first medical contact should be treated with fibrinolytic therapy within 30 minutes of hospital presentation as a systems goal unless fibrinolytic therapy is contraindicated (Level of Evidence: B)


2007 ACC/AHA STEMI Focused Update

However, fibrinolysis generally preferred when Invasive strategy not an option

– Vascular access difficulties

– No access to skilled PCI lab

Delay to invasive strategy– Prolonged transport

– Door-to-balloon time >90 min

– >1 hr vs fibrinolysis (fibrin-specific agent) now

No Preference for Either Strategy If Presentation Is 3 hr and There Is No Delay in Invasive Strategy

Adapted with permission from Antman EM, et al. J Am Coll Cardiol. 2004;44:671-719.Photo courtesy of ACC/AHA guidelines for STEMI slide set. http://www.cardiosource.com/srch/results.asp?searchterm=STEMI+PowerPoint+Slides&parsedquery+&x+10&y=5. Accessed January 10, 2008.

Determine Whether Fibrinolysis or PCI Is Preferred

Determine Whether Fibrinolysis or PCI Is Preferred (cont.)

However, invasive strategy generally preferred when Skilled PCI lab is available with surgical backup

– Door-to-balloon time <90 min

High risk from STEMI– Cardiogenic shock*, Killip class ≥III

Contraindications to fibrinolysis, including increased risk of bleeding and ICH

Late presentation– >3 hr from symptom onset

Diagnosis of STEMI is in doubt*PCI strongly preferred, but if immediate PCI not available/transfer for PCI delayed and presentation ≤3 hours, treat with fibrinolytic therapy and transfer to a skilled PCI lab. Adapted from Antman EM, et al. J Am Coll Cardiol. 2004;44:671-719.

Photo courtesy of ACC/AHA guidelines for STEMI slide set. http://www.cardiosource.com/srch/results.asp?searchterm=STEMI+PowerPoint+Slides&parsedquery+&x+10&y=5. Accessed January 10, 2008.

No Preference for Either Strategy If Presentation Is 3 hr and There Is No Delay in Invasive Strategy

Primary PCI vs Thrombolysis in STEMI: Quantitative Analysis (23 RCTs*, N=7739)

Adapted with permission from Keeley EC, et al. Lancet. 2003;361:13-20.

0

5

10

25

15

20

Fre

qu

ency

, %

Short-term outcomes(4–6 wk)

Death

P=.0002

NonfatalMI

P<.0001

RecurrentIschemia

P<.0001

Hemor-rhagicStroke

P<.0001

MajorBleed

P=.032

PCI

Thrombolytic therapy

Death, Nonfatal

Reinfarction,or Stroke

P<.0001

*The criterion for time to treatment was 6 h or less in 9 of the trials, 12 h in 13 trials, and up to 36 h in the SHOCK trial.

NRMI: Advantage of PCI Compared With Fibrinolysis Decreases as PCI-Related Delay Increases

Adapted with permission from Pinto DS, et al. Circulation. 2006;114:2019-2025.

Od

ds

of

Dea

th W

ith

F

ibri

no

lysi

s

PCI-Related Delay (door-to-balloon–door-to-needle time), min

PC

I B

ett

er

Fib

rin

oly

sis

Be

tte

r

2.0

1.5

1.25

1.0

0.8

0.560 75 90 105 114 135 150 165 180

Door to Balloon (D2B): An Alliance for Quality Campaign

Door to Balloon (D2B) Campaign—joint program of ACC, AHA, and other health organizations

Aims to increase percentage of AMI patients who receive primary angioplasty within 90 minutes of hospital presentation to 75%; current figures indicate only 35% achieve this goal

D2B implementation kit contains 6 evidence-based strategies for reducing door-to-balloon times

D2B: An Alliance for Quality Web site. http://www.d2balliance.com. Accessed December 27, 2007.

*P<.05 for all.

Bradley EH, et al. N Engl J Med. 2006;355:2308-2320.

Door to Balloon (D2B): 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

Anticoagulants as Ancillary Therapy to Reperfusion Therapy

● Patients undergoing reperfusion with fibrinolytics should receive anticoagulant therapy for a minimum of 48 hours and preferably for the duration of the index hospitalization, up to 8 days (regimens other than UFH are recommended if anticoagulant therapy is given for more than 48 hours because of the risk of heparin-induced thrombocytopenia with prolonged UFH treatment)

● Anticoagulants regimens with established efficacy include:

● UFH

● Enoxaparin

● Fondaparinux

New Class I Recommendation



Anticoagulants

● It is reasonable for patients with STEMI who do not undergo reperfusion therapy to be treated with anticoagulant therapy (non-UFH regimen) for the duration of the index hospitalization, up to 8 days (Level of Evidence: B). Convenient strategies that can be used include those with LMWH (Level of Evidence: C) or fondaparinux (Level of Evidence: B) using the same dosing regimens as for patients who receive fibrinolytic therapy

Modified Class IIa Recommendation



Main Results From ExTRACT–TIMI 25Primary End Point:

Death or nonfatal re-MI by 30 daysMain Secondary End Point:

Death, nonfatal re-MI, or urgent revascularization by 30 days

12.0

9.9

UFH UFH

ENOX ENOX

14.5

11.7

%%

RR=0.83P<.001

RR=0.81P<.001

12

9

6

3

0

Days Days0 5 10 15 20 25 30 0 5 10 15 20 25 30

12

9

6

3

0

15

Adapted with permission from Antman EM, et al. N Engl J Med. 2006;354:1477-1488.

• Major bleeding at 30 days: 1.4% with UFH vs 2.1% with enoxaparin (P<.001)

• ICH: 0.7% for UFH vs 0.8% for enoxaparin (P=.14)

RR=0.88P=.02

ExTRACT–TIMI 25: For Every 1000Patients Treated With Enoxaparin vs UFH

Eve

nts

/100

0 P

atie

nts

Nonfatal reMI

Urgent Revasc. Death

Nonfatal TIMI Major Bleed

(No increase in nonfatal ICH)

Antman EM, et al. N Engl J Med. 2006;354:1477-1488.Adapted with permission from clinicaltrialresults.org.

-15

-7 -6

4

-20

-15

-10

-5

0

5

12,092 patients presenting with STEMI within 24 hours of symptom onset (shortened to 12 hours of symptom onset midway through trial)

Randomized. Blinded. Factorial.28% female; mean age, 62 years; mean follow-up, 3-6 months

OASIS-6 Trial: Study Design

Fondaparinuxn=2823

2.5 mg/day for up to 8 days or hospital discharge

Placebon=2835

Fondaparinux n=3213

2.5 mg/day for up to 8 days or hospital discharge

UFHn=3221

Primary end point: composite of death or reinfarction at 30 days Secondary end point: composite of death or reinfarction at 9 days and at final follow-

up

Stratum 1 (No UFH)n=5658

Stratum 2 (UFH)n=6434

Yusuf S, et al. JAMA. 2006;295:1519-1530.Adapted with permission from www.clinicaltrialresults.org.

OASIS-6 Trial: ResultsF

req

uen

cy

15%

Primary End Point: Death/Reinfarction (%)

P=.008 P=.003 P=.008

12%

9%

6%

3%

0%

9.7%

11.2%

7.4%

8.9%

13.4%

14.8%

30 days 9 days 3-6 months

Fondaparinux (n=6036) Control (n=6056)

14%

Reduction in Death/MI at 30 days: Stratum 1 (No UFH Indicated)

P<.05

Reduction in Death/MI: Stratum 2(UFH Indicated)

P=NS

p=0.97p=0.97

12%

10%

8%

6%

4%

2%

0%

11.2%

14%

Fondaparinux Placebo

14%

12%

10%

8%

6%

4%

2%

0% Fondaparinux UFH

8.3% 8.7%

Yusuf S, et al. JAMA. 2006;295:1519-1530.Adapted with permissionfrom clinicaltrialresults.org.

Severe Bleeding at 9 Days

Fonda- Placebo/UFH

HR P

All cases 1.0% 1.3% 0.77 .13

Stratum 1 vs placebo

1.0% 1.6% 0.63 .06

Stratum 2 vs UFH 1.1% 1.1% 0.95 .82

OASIS-6: PCI Substudy at 30 Days

Guiding catheter thrombosis in the primary PCI cohort occurred more often with fondaparinux compared with control (n=22 vs n=0, P<.001)

Primary End Point of Death or MI in Primary PCI Cohort (%)

P=.04

Yusuf S, et al. JAMA. 2006;295:1519-1530.Adapted with permission from www.clinicaltrialresults.org.

6.0%

4.9%

0%

2%

4%

6%

8%

Fondaparinux Control

HORIZONS AMI: Bivalirudin vs Heparin + GP IIb/IIIa for Primary PCI in STEMI

aNot related to CABG; bMACE = All-cause death, reinfarction, ischemic TVR or stroke.

Stone GW, et al. Presented at: Transcatheter Cardiovascular Therapeutics 2007; October 20-25, 2007; Washington, DC.

Diff = 0.0% [-1.6, 1.5] RR = 0.99 [0.76, 1.30]

Psup = 1.00

Diff = -3.3% [-5.0, -1.6] RR = 0.60 [0.46, 0.77]

PNI ≤ .0001

Psup ≤ .0001

Diff = -2.9% [-4.9, -0.8]RR = 0.76 [0.63, 0.92]

PNI ≤ .0001

Psup = .006

1 end point 1 end point0

5

10

20

15

12.1

9.2 8.3

4.9 5.5 5.4

Net adverse clinical events

Major bleedinga MACEb

30-d

ay e

ven

t ra

tes

(%)

Bivalirudin monotherapy (n=1800)Heparin + GP IIb/IIIa inhibitor (n=1802)

Thienopyridines

● Clopidogrel 75 mg per day orally should be added to aspirin in patients with STEMI regardless of whether they undergo reperfusion with fibrinolytic therapy or do not receive reperfusion therapy. Treatment with clopidogrel should continue for at least 14 days

2004 Class I Recommendation (remains current)● In patients taking clopidogrel in whom CABG is planned, the drug

should be withheld for at least 5 days, and preferably for 7 days, unless the urgency for revascularization outweighs the risks of excess bleeding




Thienopyridines (cont.)

● In patients less than 75 years of age who receive fibrinolytic therapy or who do not receive reperfusion therapy, it is reasonable to administer an oral loading dose of clopidogrel 300 mg (No data are available to guide decision making regarding an oral loading dose in patients 75 years of age or older)

● Long-term maintenance therapy (eg, 1 year) with clopidogrel (75 mg per day orally) is reasonable in STEMI patients regardless of whether they undergo reperfusion with fibrinolytic therapy or do not receivereperfusion therapy

New Class IIa Recommendations



CLARITY- TIMI 28 Trial: Study Design

Fibrinolytic, ASA, Heparin

Clopidogrel300 mg + 75 mg qd

Coronary Angiogram(2-8 days)

Primary end point:Occluded artery (TIMI flow grade 0/1) or death/MI by time of angio

Randomized

Placebo

Double-blind, randomized, placebo-controlled trial in3491 patients, aged 18-75 yrs, with STEMI <12 hours

StudyDrug

30-day clinical follow-up

Open-labelclopidogrelper MD in

both groups

Sabatine MS, et al. N Engl J Med. 2005;352:1179-1189.

CLARITY–TIMI 28: Clopidogrel 300 mg/75 mg qd vs Placebo With Thrombolysis for STEMI (n = 3491)

PlaceboClopidogreln=1752 n=1739

36%Odds Reduction

15.0

21.7

Occ

lud

ed A

rter

y o

r D

eath

/MI,

%

0

5

10

15

20

25

Days

En

d P

oin

t, %

0

5

10

15

0 5 10 15 20 25 30

Placebo

Clopidogrel

Odds Ratio: 0.80(95% CI, 0.65-0.97)

P=.03

20%

CV Death, MI, RI Urg Revasc

Primary End Point: Occluded Artery (or Death/MI Through

Angio/HD)

Adapted with permission from Sabatine MS, et al. N Engl J Med. 2005;352:1179-1189.

P <.001

COMMIT/CCS-2: Effect of Clopidogrel 75 mg qd vs Placebo (n = 45,852)

9% (SE 3) relative risk reduction (P=.002)

Placebo + ASA: 2310events (10.1%)

Clopidogrel + ASA: 2121 events (9.2%)

Days Since Randomization (up to 28 days)

Eve

nt,

%

9

8

7

6

5

4

3

2

1

00

a All patients received aspirin 162 mg/d.SE = standard error.Adapted with permission from COMMIT Collaborative Group. Lancet. 2005;366:1607-1621.

Mo

rtal

ity,

%

Days Since Randomization (up to 28 days)

Placebo + ASA: 1845 deaths (8.1%)

Clopidogrel + ASA: 1726 deaths (7.5%)

7% (SE 3) relative risk reduction (P=.03)

7

6

5

4

3

2

1

07 14 21 28 0 7 14 21 28

Death, Re-MI, or Stroke Death in the Hospital

CLARITY–TIMI 28 and COMMIT/CCS-2:Intracranial Hemorrhage and Major Bleeding

CLARITY–TIMI 281

ClopidogrelClopidogreln=1733 (%)n=1733 (%)

PlaceboPlacebon=1719 (%)n=1719 (%) PP Value Value

ICH 8 (0.5) 12 (0.7) .38

Major Bleeding 23 (1.3) 19 (1.1) .64

30-day Major Bleeding 33 (1.9) 30 (1.7) .80

COMMIT-CCS-22

Clopidogreln=22,961 (%)

Placebon=22,891 (%) P Value

ICH 55 (0.2) 56 (0.2) .90

Major Bleeding 134 (0.6) 125 (0.5) .59

1. Sabatine MS, et al. N Engl J Med. 2005;352:1179-1189.2. Chen Z, et al. Lancet. 2005;366:1607-1621.

.142.83.0Other cardiac arrest

<.000013.95.0Cardiogenic shock

.0013.02.5Ventricular fibrillation

.0012.52.0Reinfarction

.697.87.7All-cause mortality

.109.99.4Death, reinfarction, or cardiac arrest

PPlacebo, n=22,923

Metoprolol, n=22,929

End Point (%)

COMMIT/CCS-2: Metoprolol Results

COMMIT = ClOpidogrel & Metoprolol in Myocardial Infarction Trial.

Adapted with permission from Chen ZM, et al. Lancet. 2005;366:1622-1632.

Implications for the ED

Lytics are underused, even when preference for PPCI is accepted

Lytic therapy can be optimized with proper use of adjunctive medications– Enoxaparin

– Clopidogrel

Beta blockers should be used appropriately

-Blockers

Oral -blocker therapy should be initiated in the first 24 hours for patients who do not have any of the following:

– Signs of heart failure

– Evidence of a low output state

– Increased riska for cardiogenic shock

– Other relative contraindications to -blockade (PR interval >0.24 second, second- or third-degree heart block, active asthma, or reactive airway disease)

Modified Class I Recommendation



a Risk factors for cardiogenic shock: age >70 years, systolic blood pressure <120 mm Hg, sinus tachycardia >110 bpm or heart rate <60 bpm, and increased time since onset of symptoms of STEMI.

-Blockers (cont.)

IV -blockers should not be administered to STEMI patients who have any of the following:

– Signs of heart failure

– Evidence of a low output state

– Increased riska for cardiogenic shock,

– Other relative contraindications to -blockade (PR interval >0.24 second, second- or third-degree heart block, active asthma, or reactive airway disease)

New Class III Recommendation



a Risk factors for cardiogenic shock: age >70 years, systolic blood pressure <120 mm Hg, sinus tachycardia >110 bpm or heart rate <60 bpm, and increased time since onset of symptoms of STEMI.

Anticoagulants as Ancillary Therapy to Reperfusion Therapy in PCI

● For patients undergoing PCI after having received an anticoagulant regimen, the following dosing recommendations should be followed:

● For prior treatment with UFH, administer additional boluses of UFH as needed to support the procedure, taking into account whether GP IIb/IIIa receptor antagonists have been administered. Bivalirudin may also be used in patients treated previously with UFH

● For prior treatment with enoxaparin, if the last SC dose was administered within the prior 8 hours, no additional enoxaparin should be given; if the last SC dose was administered at least 8 to 12 hours earlier, an IV dose of 0.3 mg per kg of enoxaparin should be given

● For prior treatment with fondaparinux, administer additional IV treatment with an anticoagulant possessing anti-IIa activity, taking into account whether GP IIb/IIIa receptor antagonists have been administered




PCI After Fibrinolysis or for Patients Not Undergoing Primary Reperfusion

Modified Class IIb Recommendation PCI of a hemodynamically significant stenosis in a patent

infarct artery >24 hours after STEMI may be considered as part of an invasive strategy

New Class III Recommendation PCI of a totally occluded infarct artery >24 hours after

STEMI is not recommended in asymptomatic patients with 1- or 2-vessel disease if they are hemodynamically and electrically stable and do not have evidence of severe ischemia



Antiplatelet Therapy: Clopidogrel

Modified Class I Recommendations ● A loading dose of clopidogrel, generally 600 mg, should

be administered before or when PCI is performed● In patients undergoing PCI within 12 to 24 hours of

receiving fibrinolytic therapy, a clopidogrel oral loading dose of 300 mg may be considered

King SB III, et al. J Am Coll Cardiol. doi:10.1016/j.jacc.2007.10.002.

2007 ACC/AHA/SCAI PCI Focused Update

Antiplatelet Therapy: Clopidogrel (cont.)

Modified Class IIa Recommendation

● If clopidogrel is given at the time of the procedure, supplementation with GP IIb/IIIa receptor antagonists can be beneficial

Class IIa Recommendation (No Change)● For patients with an absolute contraindication to aspirin,

it is reasonable to give a 300 mg to 600 mg loading dose of clopidogrel, administered at least 6 hours before PCI, and/or GP IIb/IIIa antagonists, administered at the time of PCI

King SB III, et al. J Am Coll Cardiol. doi:10.1016/j.jacc.2007.10.002.

2007 ACC/AHA/SCAI PCI Focused Update

DES vs BMS in STEMI: Meta-analysisPrimary Efficacy End Point: Reintervention

Reintervention = target lesion revascularization.

Reproduced with permission from Kastrati A, et al. Eur Heart J. 2007;28:2706-2713.

13.3%

5.0%

13.3%

5.0%

DES vs BMS in STEMI: Meta-analysisPrimary Safety End Point: Stent Thrombosis

Reproduced with permission from Kastrati A, et al. Eur Heart J. 2007;28:2706-2713.

PCI without stenting

– ASA 75-162 mg/d indefinitely

and– Clopidogrel 75 mg/d for at least 14 d

Bare-metal stent

– ASA 162-325 mg/d for at least 1 mo, 75-162 mg/d indefinitely

and– Clopidogrel 75 mg/d for at least 1 mo, ideally up to 1 y

Drug-eluting stent

– ASA 162-325 mg/d for at least 3 (sirolimus) to 6 (paclitaxel) mo, 75-162 mg/d indefinitely

and – Clopidogrel 75 mg/d for at least 1 y


Antiplatelet Therapy for Post-PCI PatientsClass I Recommendations


Secondary Prevention: ClopidogrelNew Class I Recommendation

For all STEMI patients not undergoing stenting (medical therapy alone or PTCA without stenting), treatment with clopidogrel should continue for at least 14 days

New Class IIa Recommendation Long-term maintenance therapy (eg, 1 year) with clopidogrel

(75 mg per day orally) is reasonable in STEMI patients regardless of whether they undergo reperfusion with fibrinolytic therapy or do not receive reperfusion therapy



Secondary Prevention: Additional Recommendations

Smoking cessation

– At each visit, every tobacco user and family members who smoke should be advised to quit (Class I, B)

– Exposure to environmental tobacco smoke at work and at home should be avoided (Class I, B)

Statin goal

– LDL-C <100 mg/dL (Class I, A)

– Consider LDL-C <70 mg/dL (Class IIa, A)

Daily physical activity 30 min/d, min 5 d/wk (Class I, B)

Annual influenza immunization (Class I, B)



Optimal medical care of STEMI begins in the prehospital setting, continues in the ED, and culminates in a prompt and informed decision about reperfusion strategy.

Optimal outcomes in STEMI can be achieved only with a multidisciplinary approach. The ACC/AHA GLs invest initial decisionmaking authority in the emergency physician.

Optimal medical care of STEMI begins in the prehospital setting, continues in the ED, and culminates in a prompt and informed decision about reperfusion strategy.

Optimal outcomes in STEMI can be achieved only with a multidisciplinary approach. The ACC/AHA GLs invest initial decisionmaking authority in the emergency physician.

Conclusion: STEMIConclusion: STEMI

Summary

● Acute therapy in STEMI focuses on reperfusion and antithrombotic therapy – new ACC/AHA guidelines provide current recommendations

● Long-term treatment involves aggressive multifactorial lifestyle modification and both antithrombotic and anti-ischemic therapies

stemi-wrap on evidence-based management of stemi: the emergency department perspective charles v....

Documents

stemi n stemi

minutes n stemi

stemi n pathophys

stemi n accounts

stemi n pharmacologic

stemi diagnosis

p4p n accounts

minutes slide