Acls Fmi 2009

ACLS 2009Acute Coronary Syndromes

M. LaCombeMDFMR

June 3, 2009

Our first case:

Chief Complaint: 30 minutes of squeezing substernal chest pain

History of Present Illness: A 60-year-old hypertensive diabetic male presents to the emergency room (ER) with 30 minutes of

squeezing substernal chest pain, relieved by sublingual nitroglycerin and nasal oxygen.

Risk factors: positive for hypertension and diabetes mellitus

Physical Findings:

Age: 60Gender: MaleWeight: 60 kg

Blood Pressure: 130/76 mm HgPulse: 86 bpm

Head and Neck: Normal jugular venous pressureChest and Lungs: clear

Cardiac Exam: Regular rhythm, no murmurs, gallopsExtremities: 2+ symmetric

EKG:

Labs:

troponin is 4.2

(what other labs are absolutely essential in this case?)

Stool for occult blood

renal function studies

How will you treat this patient?

Times to remember

• 10 minutes time for ED eval• 30 minutes door to needle• 90 minutes door to balloon• 3 hours (symptom onset) Fibrinolytic vs.

PCI therapy• 12 hours (symptom onset) Time limit for

revascularization therapies as supported by data

Initial Therapy/Recognition

• Starts in transport to ED– O2– Aspirin– Nitro– Morphine– Beta Blockers?

–12 lead EKG

Therapy and recognition in ED

• 12 lead EKG Will be used to stratify patients into treatment groups

• O2, ASA, Nitro, Morphine MONA• Physical exam• Cardiac biomarkers troponins

• 10 minute time frame

Treatment Groups Stratification

• ST-elevation MI (STEMI) ST-segment elevation or presumed new LBBB in 2 or more contiguous precordial or limb leads

• UA/non-ST-elevation MI (NSTEMI) ischemic ST-segment depression or dynamic T wave inversion with pain. Transient ST-segment elevation.

• Normal or nondiagnostic changes with pain

Copyright ©2005 American Heart Association

Circulation 2005;112:IV-89-IV-110

Acute Coronary Syndromes Algorithm

Medications to Consider for a NONSTEMI:

• Nitroglycerine • Beta blockers• Clopidogrel• Heparin• Glycoprotein IIb/IIIA inhibitors

Should be managed with invasive strategy if:

• New ST-segment depression and positive troponins

• Persistent or recurrent symptoms

• Hemodynamic instability or VT

• Depressed LV function (ejection fraction <40%)

• ECG or functional study that suggests multivessel CAD

Definite ACSDefinite ACSDefinite ACSDefinite ACSPossible ACSPossible ACS

(–) ECG;(–) ECG;Normal biomarkersNormal biomarkers

(–) ECG;(–) ECG;Normal biomarkersNormal biomarkers

Observe; repeat ECG,Observe; repeat ECG, markers at 4-8 hmarkers at 4-8 h

Observe; repeat ECG,Observe; repeat ECG, markers at 4-8 hmarkers at 4-8 h

No recurrent pain;No recurrent pain;(–) follow-up studies(–) follow-up studiesNo recurrent pain;No recurrent pain;

(–) follow-up studies(–) follow-up studiesRecurrent pain;Recurrent pain;

(+) follow-up studies(+) follow-up studiesRecurrent pain;Recurrent pain;

(+) follow-up studies(+) follow-up studies

Stress test; Stress test; LV LVfunction if ischemiafunction if ischemia

Stress test; Stress test; LV LVfunction if ischemiafunction if ischemia

(–) test: outpatient follow-up(–) test: outpatient follow-up(–) test: outpatient follow-up(–) test: outpatient follow-up

(+) test(+) test(+) test(+) test

Use 2007 NSTE ACS Use 2007 NSTE ACS GuidelinesGuidelines

Use 2007 NSTE ACS Use 2007 NSTE ACS GuidelinesGuidelines

ST ST

Use 2004Use 2004Updated MIUpdated MI GuidelinesGuidelines

Use 2004Use 2004Updated MIUpdated MI GuidelinesGuidelines

No ST No ST

ST-T ST-T ’s, ’s, def. pain,def. pain,markersmarkers

ST-T ST-T ’s, ’s, def. pain,def. pain,markersmarkers

ACS Risk GuidedACS Risk GuidedAlgorithmAlgorithm

Symptoms Suggestive of ACSSymptoms Suggestive of ACSSymptoms Suggestive of ACSSymptoms Suggestive of ACS

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 performed/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

17

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 performed/administered SINCE IT IS NOT HELPFUL AND MAY BE HARMFUL

Applying Classification of Recommendations and Level of Evidence

Level A: Recommendation based on evidence from multiple randomized trials or meta-analyses Multiple (3-5) population risk strata evaluated; General consistency of direction and magnitude of effect

Level B: Recommendation based on evidence from a single randomized trial or non-randomized studies Limited (2-3) population risk strata evaluated

Level C: Recommendation based on expert opinion, case studies, or standard-of-care Very limited (1-2) population risk strata evaluated

ST-segment Elevation

Acute Evaluation of ACS

Chest pain or Short of Breath

NSTEMI

ST-segment Depression

– + +

Presentation

ECG

Diagnosis

Normal

Markers

STEMI

–+

Rule-Out

Adapted from: Anderson JL. J Am Coll Cardiol 2007;50:e1-157

Initial Evaluation - Risk Stratification

12-lead ECG within 10 min for all patients with chest pain or symptoms suggestive of ACSEarly risk stratification by symptoms, physical findings, ECG, cardiac markersCardiac markers, Troponins and CK-MB, for initial assessment Use of risk stratification models (TIMI, PURSUIT, GRACE) can be useful to assist in decision making for treatment options

12-lead ECG within 10 min for all patients with chest pain or symptoms suggestive of ACSEarly risk stratification by symptoms, physical findings, ECG, cardiac markersCardiac markers, Troponins and CK-MB, for initial assessment Use of risk stratification models (TIMI, PURSUIT, GRACE) can be useful to assist in decision making for treatment options

IIII IIaIIaIIaIIa IIbIIbIIbIIb IIIIIIIIIIII

JACC 2007.JACC 2007.

20

Anti-Ischemic Therapy

It is reasonable to administer intravenous beta blockers at the time of presentation for hypertension to UA/NSTEMI patients who do not have 1 or more of the following: 1) signs of HF, 2) evidence of a low-output state, 3) increased risk* for cardiogenic shock, or 4) other relative contraindications to beta blockade (PR interval greater than 0.24 s, second or third degree heart block, active asthma, or reactive airway disease).

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

*Risk factors for cardiogenic shock (the greater the number of risk factors present, the higher the risk of developing cardiogenic shock): age greater than 70 years, systolic blood pressure less than 120 mmHg, sinus tachycardia greater than 110 or heart rate less than 60, increased time since onset of symptoms of UA/NSTEMI. Chen ZM, et al. Lancet 2005;366:1622–32.

I → IIa

21


It may be harmful to administer intravenous beta blockers to UA/NSTEMI patients who have contraindications to beta blockade, signs of HF or low-output state, or other risk factors* for cardiogenic shock.



New

22


Oral beta-blocker therapy should be initiated within the first 24 h for patients who do not have 1 or more of the following: 1) signs of HF, 2) evidence of a low-output state, 3) increased risk* for cardiogenic shock, or 4) other relative contraindications to beta blockade (PR interval greater than 0.24 s, second or third degree heart block, active asthma, or reactive airway disease).



Major Change

Alert:

Avoid beta blockers in ACS if there is impending cardiogenic shock!

Cardiogenic Shock: Current Concepts and Improving Outcomes Reynolds HR, Hochman JSCirculation. 2008;117:686-697

Cardiogenic Shock: Basics and Clinical ConsiderationsGowda RM, Fox JT, Khan IA Int J Cardiol. 2008;123:221-228

Cardiogenic shock (CS) is defined as a state of tissue hypoperfusion resulting from cardiac failure. Hypoperfusion may manifest as systemic hypotension, peripheral vasoconstriction and diminished pulses, decreased urine output,

decreased mental status, or significantly reduced cardiac indices (cardiac index) despite correction of preload.

CS occurs in 5% to 10% of patients hospitalized with MI (ST-segment elevated MI) and is a common cause of death in this group.

An unknown additional number of prehospital patients die from CS, making the exact incidence uncertain.

Risk factors for development of post-MI CS include older age, anterior location of MI, hypertension, diabetes, multivessel occlusions, left bundle

branch block, and prior history of cardiac disease or heart failure.Tachycardia and/or hypotension at admission predict CS in patients with

MI.

25


Because of the increased risks of mortality, reinfarction, hypertension, HF, and myocardial rupture associated with their use, nonsteroidal anti-inflammatory drugs (NSAIDs), except for ASA, whether nonselective or cyclooxygenase (COX)-2–selective agents, should be discontinued at the time a patient presents with UA/NSTEMI.


The selective COX-2 inhibitors and other nonselective NSAIDs have been associated with increased cardiovascular risk. An AHA scientific statement on the use of NSAIDs concluded that the risk of cardiovascular events is proportional to COX-2 selectivity and the underlying risk to the patient (Antman EM, et al. Use of nonsteroidal antiinflammatory drugs. An update for clinicians. A scientific statement from the American Heart Association. Circulation 2007;115:1634–42. Further discussion can be found in Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157 and in the Secondary Prevention Section of this slide set.

New

26

Antiplatelet Therapy

Aspirin should be administered to UA/NSTEMI patients as soon as possible after hospital presentation and continued indefinitely in patients not known to be intolerant of that medication.

Clopidogrel (loading dose [LD] followed by daily maintenance dose)* should be administered to UA/NSTEMI patients who are unable to take ASA because of hypersensitivity or major gastrointestinal intolerance.


*Some uncertainty exists about optimum dosing of clopidogrel. Randomized trials establishing its efficacy and providing data on bleeding risks used a loading dose of 300 mg orally followed by a daily oral maintenance dose of 75 mg. Higher oral loading doses such as 600 or 900 mg of clopidogrel more rapidly inhibit platelet aggregation and achieve a higher absolute level of inhibition of platelet aggregation, but the additive clinical efficacy and the safety of higher oral loading doses have not been rigorously established.


LD added

27

Select Management Strategy:

Initial Invasive Versus Initial Conservative Strategy

Major ChangesNew Trial Data

28

Selection of Initial Treatment Strategy: Initial Invasive Versus Conservative Strategy

Invasive Recurrent angina/ischemia at rest with low-level activities despite intensive medical therapy

Elevated cardiac biomarkers (TnT or TnI)

New/presumably new ST-segment depression

Signs/symptoms of heart failure or new/worsening mitral regurgitation

High-risk findings from noninvasive testing

Hemodynamic instability

Sustained ventricular tachycardia

PCI within 6 months

Prior CABG

High risk score (e.g., TIMI, GRACE)

Reduced left ventricular function (LVEF < 40%)

Conservative

Low risk score (e.g., TIMI, GRACE)

Patient/physician presence in the absence of high-risk features

29

Risk Scores

TIMI GRACE

Histo

ry

AgeHypertensionDiabetesSmoking↑ CholesterolFamily historyHistory of CAD

Age

Pre

sen

tatio

n

Severe anginaAspirin within 7 daysElevated markersST-segment deviation

Heart rateSystolic BPElevated creatinineHeart failureCardiac arrestElevated markersST-segment deviation

Antman EM, et al. JAMA 2000;284:835–42. Eagle KA, et al. JAMA 2004;291:2727–33. GRACE = Global Registry of Acute Coronary Events; TIMI = Thrombolysis in Myocardial Infarction.

30

Algorithm for Patients with UA/NSTEMI Managed by an Initial Invasive Strategy

Proceed to Diagnostic Angiography

ASA (Class I, LOE: A)Clopidogrel if ASA intolerant (Class I,

LOE: A)

Diagnosis of UA/NSTEMI is Likely or Definite

Invasive StrategyInit ACT (Class I, LOE: A)

Acceptable options: enoxaparin or UFH (Class I, LOE: A) bivalirudin or fondaparinux (Class I, LOE: B)

Select Management StrategyProceed with an

Initial Conservative

Strategy

Anderson JL, et al. J Am Coll Cardiol. 2007;50:e1-e157, Figure 7. ACT = anticoagulation therapy; LOE = level of evidence.

Prior to AngiographyInit at least one (Class I, LOE: A) or

both (Class IIa, LOE: B) of the following:

ClopidogrelIV GP IIb/IIIa inhibitor

Factors favoring admin of both clopidogrel and GP IIb/IIIa inhibitor include:

Delay to AngiographyHigh Risk Features

Early recurrent ischemic discomfort

31

Initial Invasive Strategy: Antiplatelet Therapy

For UA/NSTEMI patients in whom an initial invasive strategy is selected, antiplatelet therapy in addition to ASA should be initiated before diagnostic angiography (upstream) with either clopidogrel (loading dose followed by daily maintenance dose)* or an IV GP IIb/IIIa inhibitor.

Abciximab as the choice for upstream GP IIb/IIIa therapy is indicated only if there is no appreciable delay to angiography and PCI is likely to be performed; otherwise, IV eptifibatide or tirofiban is the preferred choice of GP IIb/IIIa inhibitor.†


*Some uncertainty exists about optimum dosing of clopidogrel. Randomized trials establishing its efficacy and providing data on bleeding risks used a loading dose of 300 mg orally followed by a daily oral maintenance dose of 75 mg. Higher oral loading doses such as 600 or 900 mg of clopidogrel more rapidly inhibit platelet aggregation and achieve a higher absolute level of inhibition of platelet aggregation, but the additive clinical efficacy and the safety of higher oral loading doses have not been rigorously established; †Factors favoring administration of both clopidogrel and a GP IIb/IIIa inhibitor include: delay to angiography, high-risk features, and early ischemic discomfort.


32

Clopidogrel in Unstable angina to preventRecurrent ischemic Events (CURE)

•12,562 patients within 24 h UA/NSTEMI

•Placebo vs clopidogrel (LD 300 mg → 75 mg qd)

•Other meds: ASA

•↓ CV death, MI, or stroke, rate of recurrent ischemia & revasc with clopidogrel

•↑ Major (non–life-threatening) bleeding with clopidogrel

•No routine inv strategy, 23% revasc during initial admission

•Although well tolerated, < 10% GP IIb/IIIa + ASA + clopidogrel + heparin use in study patients

Yusuf S, et al. N Engl J Med 2001;345:494–502.

33

Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using InTegrilin (PURSUIT)


•Low-dose eptifibatide (n=1,487) vs high-dose eptifibatide (n=4,722) vs placebo (n=4,739)

•Other meds: ASA, heparin

•↓ Death/MI @ 96 hours, 7 d, 30 d with eptifibatide

― 1.5% ARR 4–30 d

― ↑ major bleeding

― no diff stroke

•↑ Event rate in 11% of patients not treated with concomitant heparin

The PURSUIT Trial Investigators. N Engl J Med 1998;339:436–43. Boersma E, et al. Circulation 2000;101:2557–67. ARR= absolute risk reduction.

34

Platelet Receptor Inhibition in Ischemic Syndrome Management

in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS)


•Tirofiban alone, UFH alone, or both for 48–108 h.

•Tirofiban-alone arm discontinued d/t ↑ mortality rate.

•↓ Death, MI, or refractory ischemia at 7 d, 30 d & 6 mo by tirofiban + heparin

•High rate of angio could have contributed to important ↓ in event rates

•Recommend: Tirofiban + heparin for medical rx or during PCI

PRISM-PLUS Study Investigators. N Engl J Med 1998;338:1488–97.

30-Day Death or Nonfatal MIRisk Ratio and 95% CI

Placebo BetterGP IIb/IIIa Inhibitor Better

Trial

Pooled 11.5%

PlaceboGP IIb/IIIa Inhibitor

10.7%29,855

n

0.92 (0.86, 0.995)P=.037

PRISM-PLUS 11.9% 10.2%1,915

PURSUIT 15.7% 14.2%9,461

PARAGON A 11.7% 11.3%2,282

7.1%PRISM 5.8%3,232

0.5 1.0 1.5

PARAGON B 11.4% 10.5%5,165

GUSTO-IV ACS

8.0% 8.7%7,800

GP IIb/IIIa Inhibition for Non–ST-Elevation ACS

Boersma E, et al. Lancet. 2002;359:189-198.

CI = confidence interval.

Benefits of GP IIb/IIIa by Troponin Status in Clinical Trials

Newby KL, et al. Circulation. 2001;103:2891-2896.

TnT-NegativeTnT-Positive

PARAGON-B

PRISM

CAPTURE

Combined

0.125 1 20.5 0.125 1 20.5GP IIb/IIIa

BetterGP IIb/IIIa

WorseGP IIb/IIIa

BetterGP IIb/IIIa

Worse

ISAR-REACT 2: Cumulative Incidence of Death, MI, or Urgent TVR in Subsets

With and Without Elevated Troponin levels (>0.03 µg/L)

ISAR-REACT 2 = Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 2.

Adapted with permission from Kastrati A, et al. JAMA. 2006;295:1531-1538.

20

15

10

5

0

0 5 10 15 20 25 30Days After Randomization

Cum

ulati

ve R

ate

ofPr

imar

y En

d Po

int,

%

Placebo Group (n=1010)Abciximab Group (n=1012)

Troponin >0.03 µg/LLog-Rank P=.02

Troponin <0.03 µg/LLog-Rank P=.98

The Bottom Line for IV GP IIb IIIa Inhibitors

• Consider starting upfront (ED) when patients at highest risk undergoing early invasive

• Consider in lab if PCI and not started upfront • Clopidogrel complementary, not competitor• Dose appropriately for renal function

39

Initial Invasive Strategy:Anticoagulant TherapyAnticoagulant therapy should be added to antiplatelet therapy in UA/NSTEMI patients as soon as possible after presentation.

•For patients in whom an invasive strategy is selected, regimens with established efficacy at a Level of Evidence: A include enoxaparin and unfractionated heparin (UFH), and those with established efficacy at a Level of Evidence: B include bivalirudin and fondaparinux.



New Drugs

40

Initial Conservative Strategy

Major Changes•New Drugs•Longer Duration of Rx•Revised Algorithm

41

Init clopidogrel (Class I, LOE: A) Consider adding IV eptifibatide or tirofiban (Class

IIb, LOE: B)

Conservative StrategyInit anticoagulant therapy (Class I, LOE: A):

Acceptable options: enoxaparin or UFH (Class I, LOE: A) or fondaparinux (Class I, LOE: B), but

enoxaparin or fondaparinux are preferable (Class IIa, LOE: B)

Select Management Strategy

ASA (Class I, LOE: A)Clopidogrel if ASA intolerant (Class I, LOE: A)

Diagnosis of UA/NSTEMI is Likely or Definite

Algorithm for Patients with UA/NSTEMI Managed by an Initial Conservative Strategy

Proceed with Invasive Strategy

(Continued)Anderson JL, et al. J Am Coll Cardiol. 2007;50:e1-e157, Figure 8. ACT = anticoagulation therapy; LOE = level of evidence.

42

Any subsequent events necessitating angiography?

EF greater than 40%

Evaluate LVEF

Low Risk

Cont ASA (Class I, LOE A) Cont clopidogrel (Class I, LOE A) and ideally up to 1 yr (Class I, LOE B)

DC IV GP IIb/IIIa if started previously (Class I, LOE A) DC ACT (Class I, LOE A)

(Class I, LOE: B)

Proceed to Dx Angiography

Yes

EF 40% or less Stress Test

(Class I, LOE: A)

No

Not Low Risk

(Class IIa, LOE: B)

Algorithm for Patients with UA/NSTEMI Managed by an Initial Conservative Strategy

(Continued)

Anderson JL, et al. J Am Coll Cardiol. 2007;50:e1-e157, Figure 8. ACT = anticoagulation therapy; LOE = level of evidence.

(Class I, LOE: A)

(Class IIa, LOE: B)

(Class I,

LOE: B)

(Class I, LOE: A)

43

Initial Conservative Strategy:Antiplatelet Therapy

For UA/NSTEMI patients in whom an initial conservative (i.e., noninvasive) strategy is selected, clopidogrel (loading dose followed by daily maintenance dose)* should be added to ASA and anticoagulant therapy as soon as possible after admission and administered for at least 1 month (Level of Evidence: A) and ideally up to 1 year. (Level of Evidence: B)


*Some uncertainty exists about optimum dosing of clopidogrel. Randomized trials establishing its efficacy and providing data on bleeding risks used a loading dose of 300 mg orally followed by a daily oral maintenance dose of 75 mg. Higher oral loading doses such as 600 or 900 mg of clopidogrel more rapidly inhibit platelet aggregation and achieve a higher absolute level of inhibition of platelet aggregation, but the additive clinical efficacy and the safety of higher oral loading doses have not been rigorously established.


44

Initial Conservative Strategy:Antiplatelet Therapy

For UA/NSTEMI patients in whom an initial conservative (i.e., noninvasive) strategy is selected, it may be reasonable to add eptifibatide or tirofiban to anticoagulant and oral antiplatelet therapy.

Abciximab should not be administered to patients in whom PCI is not planned.



45

Initial Conservative Strategy:Anticoagulant TherapyAnticoagulant therapy should be added to antiplatelet therapy in UA/NSTEMI patients as soon as possible after presentation.

•For patients in whom a conservative strategy is selected, regimens using either enoxaparin* or UFH (Level of Evidence: A) or fondaparinux (Level of Evidence: B) have established efficacy.

•In patients in whom a conservative strategy is selected and who have an increased risk of bleeding, fondaparinux is preferable.



*Limited data are available for the use of other low-molecular-weight heparins (LMWHs), e.g., dalteparin.

New Drugs

46

Initial Conservative Strategy:Anticoagulant TherapyFor UA/NSTEMI patients in whom an initial conservative strategy is selected, enoxaparin* or fondaparinux is preferable to UFH as anticoagulant therapy, unless CABG is planned within 24 h.


*Limited data are available for the use of other low-molecular-weight heparins (LMWHs), e.g., dalteparin.

47

Initial Conservative Strategy:Additional Management Considerations

b. If, after stress testing, the patient is classified as being at low risk, the instructions noted below should be followed in preparation for discharge:

1. Continue ASA indefinitely. (Level of Evidence: A)

2. Continue clopidogrel for at least 1 month (Level of Evidence: A) and ideally up to 1 year. (Level of Evidence: B)

3. Discontinue IV GP IIb/IIIa inhibitor if started previously. (Level of Evidence: A)

4. Continue UFH for 48 h or administer enoxaparin or fondaparinux for the

duration of hospitalization, up to 8 d, and then discontinue anticoagulant therapy. (Level of Evidence: A)


48

Long-Term Antithrombotic Therapy at Hospital Discharge after UA/NSTEMI

Medical Therapy

without Stent

Bare Metal Stent Group

Drug Eluting Stent Group

ASA 162 to 325 mg/d for at least 1 month, then 75 to 162

mg/d indefinitely (Class I, LOE: A)

&Clopidogrel 75 mg/d for at least 1 month and up to 1

year (Class I, LOE:B)

Add: Warfarin (INR 2.0 to 2.5) (Class IIb, LOE: B)

Continue with dual antiplatelet therapy as

above

Yes

No

Indication for Anticoagulation?

ASA 75 to 162 mg/d indefinitely (Class I, LOE:

A)

&

Clopidogrel 75 mg/d at least 1 month (Class I,

LOE: A) and up to 1 year (Class I, LOE: B)

ASA 162 to 325 mg/d for at least 3 to 6 months, then 75 to 162 mg/d

indefinitely (Class I, LOE: A)

&

Clopidogrel 75 mg/d for at least 1 year (Class I, LOE:

B)

Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 11. INR = international normalized ratio; LOE = level of evidence.

UA/NSTEMI Patient Groups at Discharge

New

49

Beta Blockers

Beta blockers are indicated for all patients recovering from UA/NSTEMI unless contraindicated. (For those at low risk, see Class IIa on the next slide). Treatment should begin within a few days of the event, if not initiated acutely, and should be continued indefinitely.

Patients recovering from UA/NSTEMI with moderate or severe LV failure should receive beta-blocker therapy with a gradual titration scheme.


III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII New

50

Inhibition of the Renin-Angiotensin-Aldosterone SystemACE inhibitors are reasonable for patients recovering from UA/NSTEMI in the absence of LV dysfunction, hypertension, or diabetes mellitus unless contraindicated.

ACE inhibitors are reasonable for patientswith HF and LVEF > 0.40.

In UA/NSTEMI patients who do not tolerate ACE inhibitors, an ARB can be useful as an alternative to ACE inhibitors in long-term management provided there are either clinical or radiological signs of HF and LVEF < 40%.




New

New

51

Lipid Management

Lipid management should include assessment of a fasting lipid profile for all patients, within 24 h of hospitalization.

Hydroxymethyl glutaryl-coenzyme A reductase inhibitors (statins), in the absence of contraindications, regardless of baseline LDL-C and diet modification, should be given to post-UA/NSTEMI patients, including postrevascularization patients.

For hospitalized patients, lipid-lowering medications should be initiated before discharge.




Major Changes

52

Heart Protection Study (HPS)

•20,536 patients with CHD•Simvastatin (40 mg qd) vs placebo

•↓ Total mortality by simvastatin

― ↓ Total CHD, total stroke, revascularization

― ↑ Benefit over time, irrespective of initial cholesterol level and in broad spectrum of patients (e.g., women, elderly & patients with diabetes)

•Recommend: Statin in all patients at discharge regardless of baseline LDL-C (Class I, LOE: A)

Heart Protection Collaborative Group. Lancet 2002;360:7–22.LOE = level of evidence.

53

Lipid Management

For UA/NSTEMI patients with elevated LDL-C (≥ 100 mg per dL), cholesterol-lowering therapy should be initiated or intensified to achieve an LDL-C < 100 mg per dL.Further titration to less than 70 mg per dL is reasonable. (Class IIa, Level of Evidence: A)

Therapeutic options to reduce non–HDL-C* are recommended, including more intense LDL-C–lowering therapy.



*Non-HDL-C = total cholesterol minus HDL-C

New Lower LDL-C Goal

54

PRavastatinOr atorVastatin Evaluation and Infection Therapy–

Thrombolysis In Myocardial Infarction 22 (PROVE-IT TIMI 22)

•4,162 patients within 10 d of ACS

•40 mg pravastatin vs 80 mg atorvastatin daily

•↓ All-cause death, MI, UA requiring hosp, revasc & stroke @ 2 y by atorvastatin

― Median LDL-C ↓ (62 vs 95 mg/dL)

Cannon CP, et al. N Engl J Med 2004;350:1495–504.

55

Lipid Management

Further reduction of LDL-C to < 70 mg per dL is reasonable.

If baseline LDL cholesterol is 70 to 100 mg per dL, it is reasonable to treat LDL-C to < 70 mg per dL.

Further reduction of non-HDL-C* to < 100 mg per dL is reasonable; if TG are 200 to 499 mg per dL, non- HDL-C target is < 130 mg per dL. Therapeutic options to reduce non-HDL-C* (after LDL-C lowering) include niacin† or fibrate‡ therapy.

*Non-HDL-C = total cholesterol minus HDL-C.†The combination of high-dose statin plus fibrate can increase risk for severe myopathy. Statin doses should be kept relatively low with this combination. Dietary supplement niacin must not be used as a substitute for prescription niacin. ‡Patients with very high triglycerides should not consume alcohol. The use of bile acid sequestrants is relatively contraindicated when triglycerides are greater than 200 mg per dL.




Next Case:

Chief Complaint: Subxiphoid burning sensation and dyspnea

History of Present Illness: A 48-year-old female who smokes two packs per day presents with 1 hour of a

subxiphoid burning sensation with dyspnea and diaphoresis, which are ongoing. She denies any prior

cardiovascular or gastrointestinal history.

Risk factor: positive family history of premature coronary artery disease

Age: 48Gender: Female

Blood Pressure: 170/95 mm HgPulse: 96 bpm

Head and Neck: Jugular venous pressure, 10Chest and Lungs: Clear

Cardiac Exam: Regular rhythm, normal S1/S2; S4 present

Extremities: 2+ pulses, no edema

Her EKG:

Copyright ©2005 American Heart Association Circulation 2005;112:IV-89-IV-110

Acute Coronary Syndromes Algorithm

Initial Therapy/Recognition

• Starts in transport to ED– O2– Aspirin– Nitro– Morphine– Beta Blockers?

–12 lead EKG

Therapy and recognition in ED

• 12 lead EKG Will be used to stratify patients into treatment groups

• O2, ASA, Nitro, Morphine MONA• Physical exam• Cardiac biomarkers troponins

• 10 minute time frame

Treatment Groups Stratification

• ST-elevation MI (STEMI) ST-segment elevation or presumed new LBBB in 2 or more contiguous precordial or limb leads

• UA/non-ST-elevation MI (NSTEMI) ischemic ST-segment depression or dynamic T wave inversion with pain. Transient ST-segment elevation.

• Normal or nondiagnostic changes with pain

ED Evaluation of ED Evaluation of Patients With STEMIPatients With STEMI

1. Airway, Breathing, Circulation (ABC)

2. Vital signs, general observation

3. Presence or absence of jugular venous distension

4. Pulmonary auscultation for rales

5. Cardiac auscultation for murmurs and gallops

6. Presence or absence of stroke

7. Presence or absence of pulses

8. Presence or absence of systemic hypoperfusion (cool, clammy, pale, ashen)

Brief Physical Examination in the ED


Aortic dissection

Pulmonary embolus

Perforating ulcer

Tension pneumothorax

Boerhaave syndrome

(esophageal rupture with

mediastinitis)

Differential Diagnosis of STEMI: Life-Threatening


PericarditisAtypical anginaEarly repolarizationWolff-Parkinson-White

syndromeDeeply inverted T-waves

suggestive of a central nervous system lesion or apical hypertrophic cardiomyopathy

LV hypertrophy with strain

Brugada syndrome

Myocarditis

Hyperkalemia

Bundle-branch blocks

Vasospastic angina

Hypertrophic cardiomyopathy

Differential Diagnosis of STEMI: Other Cardiovascular and Nonischemic

Gastroesophageal reflux (GERD) and spasm

Chest-wall pain

Pleurisy

Peptic ulcer disease

Panic attack

Cervical disc or neuropathic pain

Biliary or pancreatic pain

Somatization and psychogenic pain disorder


Differential Diagnosis of STEMI: Other Noncardiac

ElectrocardiogramElectrocardiogram

Show 12-lead ECG results to emergency physician

within 10 minutes of ED arrival in all patients with

chest discomfort (or anginal equivalent) or other

symptoms of STEMI.

In patients with inferior STEMI, ECG leads should

also be obtained to screen for right ventricular

infarction.



Right Ventricular InfarctionRight Ventricular Infarction

Clinical findings:Shock with clear lungs, elevated JVPKussmaul sign

Hemodynamics: Increased RA pressure (y descent)Square root sign in RV tracing

ECG:ST elevation in R sided leads

Echo:Depressed RV function

Rx:Maintain RV preloadLower RV afterload (PA---PCW)Inotropic supportReperfusion

V4R

Modified from Wellens. N Engl J Med 1999;340:381.

Cardiac-specific troponins should be used as the

optimum biomarkers for the evaluation of patients

with STEMI who have coexistent skeletal muscle

injury.

For patients with ST elevation on the 12-lead ECG

and symptoms of STEMI, reperfusion therapy

should be initiated as soon as possible and is not

contingent on a biomarker assay.

Biomarkers of Cardiac DamageBiomarkers of Cardiac Damage



00 11 22 33 44 55 66 7788

Cardiac troponin-no Cardiac troponin-no reperfusion reperfusion

Days After Onset of STEMIDays After Onset of STEMI

Mu

ltip

les

of

the

UR

LM

ult

iple

s o

f th

e U

RL

Upper reference limitUpper reference limit11

22

55

1010

2020

5050

URL = 99th %tile of URL = 99th %tile of Reference Control GroupReference Control Group

100100

Cardiac troponin-Cardiac troponin-reperfusion reperfusion

CKMB-no reperfusion CKMB-no reperfusion

CKMB-CKMB-reperfusion reperfusion

Cardiac Biomarkers in STEMICardiac Biomarkers in STEMI

Alpert et al. J Am Coll Cardiol 2000;36:959.Wu et al. Clin Chem 1999;45:1104.

STEMIST-segment elevation or

presumed new LBBB in 2 or more contiguous precordial

or limb leads

STEMI• Immediate reperfusion therapy

indicated

–Fibrinolytics –PCI

Medications for STEMI

• Clopidogrel• Beta blockers• Heparin• fibrinolytics

FibrinolysisFibrinolysis

In the absence of contraindications, fibrinolytic therapy should be administered to STEMI patients with symptom onset within the prior 12 hours.

In the absence of contraindications, fibrinolytic therapy should be administered to STEMI patients with symptom onset within the prior 12 hours and new or presumably new left bundle branch block (LBBB).

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII



In the absence of contraindications, it is reasonable to administer fibrinolytic therapy to STEMI patients with symptom onset within the prior 12 hours and 12-lead ECG findings consistent with a true posterior MI.

In the absence of contraindications, it is reasonable to administer fibrinolytic therapy to patients with symptoms of STEMI beginning in the prior 12 to 24 hours who have continuing ischemic symptoms and ST elevation > 0.1 mV in ≥ 2 contiguous precordial leads or ≥ 2 adjacent limb leads.




Fibrinolytic therapy should not be administered to

asymptomatic patients whose initial symptoms of

STEMI began more than 24 hours earlier.

Fibrinolytic therapy should not be administered to

patients whose 12-lead ECG shows only ST-

segment depression, except if a true posterior MI

is suspected.



Assessment of ReperfusionAssessment of Reperfusion

It is reasonable to monitor the pattern of ST elevation, cardiac rhythm and clinical symptoms over the 60 to 180minutes after initiation of fibrinolytic therapy.

Noninvasive findings suggestive of reperfusion include:

Relief of symptoms

Maintenance and restoration of hemodynamic and/or electrical instability

Reduction of ≥ 50% of the initial ST-segment elevation pattern on follow-up ECG 60 to 90 minutes after initiation of therapy.


Ancillary Therapy to ReperfusionAncillary Therapy to Reperfusion

Unfractionated heparin (UFH) should be given intravenously in:

Patients undergoing PCI or surgical revascularization

After alteplase, reteplase, tenecteplase

After streptokinase, anistreplase, urokinase in patients at high risk for systemic emboli.


ThienopyridinesThienopyridines

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

risk of excessive bleeding.

NOTE: Surgeons at MMC will take a patient to

the OR for bypass even if given a loading dose

of Plavix that day. This represents a change.


ACE/ARB: Within 24 HoursACE/ARB: Within 24 Hours

An ACE inhibitor should be administered orallywithin the first 24 hours of STEMI to the followingpatients without hypotension or known class ofcontraindications:

• Anterior infarction Pulmonary congestion

LVEF < 0.40

An ARB should be given to ACE-intolerant patients with either clinical or radiological signs of HF or LVEF < 0.40.



All-Cause Mortality

Years

Pro

bab

ilit

y o

f Even

t

0

0.05

0.1

0.15

0.2

0.25

0.3

0 1 2 3

0.35

0.4

4

ACE-I

Placebo

ACE-I 2995 2250 1617 892 223

Placebo 2971 2184 1521 853 138

Flather MD, et al. Lancet. 2000;355:1575–1581

OR: 0.74 (0.66–0.83)OR: 0.74 (0.66–0.83)

ACE-I: 702/2995 (23.4%)ACE-I: 702/2995 (23.4%)

Placebo: 866/2971 (29.1%)Placebo: 866/2971 (29.1%)

TRACEEchocardiographicEF 35%

AIREClinical and/or radiographic signs of HF

SAVERadionuclideEF 40%

Last Case:

A 58 y.o. man presents to the ER with a complaint of chest pain.

His EKG and initial troponin are both normal.

How will you proceed?

First, characterize the chest pain

• Where is its location?• What provokes it?• What relieves it?

Typical or classical angina:

• Is located in the center of the chest and may have textbook radiation to the arm, neck, or jaw

• Is provoked by exercise or emotion• Is relieved by rest or nitroglycerine

To establish the likelihood of your patient having an acute coronary syndrome, first determine whether:

• All three characteristics are present, and therefore the patient has typical angina

• Two of three are present, i.e. this is atypical angina

• One or none are present, i.e. this is non-anginal chest pain

Then, use the medical literature:

Diamond and Forrester: New England Journal of Medicine 1979; 300 (24): 1350 300 (24): 1350- -1358

Diamond and Forrester: New England Journal of Medicine 1979; 300 (24): 1350 300 (24): 1350- -1358

And to these probabilities, add some history:

• Family history of premature coronary disease?• Lipid profile known?• History of HTN?• Of diabetes?• Smoking?

Now, you need to use Bayes’ Theorem… that is of course unless you are like me and want a

short-cut.

Here’s a short cut:

It’s called the Fagan nomogram:

…together with your pretest probability you have estimated for

your patient.

And the likelihood ratios…for mibis, the +LR is about 2.4 and

the –LR is about .2

But look at the nomogram again! Are you convinced that stress testing is most helpful for the patient with intermediate pretest probability?

Remember, central to the ACS algorithm is the 12-lead EKG.

Which of these are acute MI’s?

And which of these is V. Tach?

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Health & Medicine

Acls Fmi 2009