Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute...

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Acute Myocardial Infarction 2017 Update Jeffrey L Anderson MD, MACP, FACC, FAHA, FHRS Distinguished Research Physician Intermountain Medical Center Heart Institute Professor of Medicine (Cardiology) University of Utah School of Medicine Salt Lake City, Utah No relevant conflicts of interest to report

Transcript of Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute...

Page 1: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

Acute Myocardial Infarction

2017 Update

Jeffrey L Anderson MD, MACP, FACC, FAHA, FHRSDistinguished Research PhysicianIntermountain Medical Center Heart Institute Professor of Medicine (Cardiology)University of Utah School of MedicineSalt Lake City, Utah

No relevant conflicts of interest to report

Page 2: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

Acute Myocardial Infarction: Introduction

Acute myocardial infarction (AMI) with or without electrocardiographic ST-segment elevation (STEMI or non-STEMI) is a common cardiac emergency with the potential for substantial morbidity and mortality. The management of AMI has improved dramatically over the past three decades and continues to evolve.

Anderson JL, Morrow DA. Acute Myocardial Infarction. NEJM 2017; 376:2053

Page 3: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

Acute Myocardial Infarction: Definition & Classification

Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome. In practice, AMI is diagnosed and assessed on the basis of clinical evaluation, the electrocardiogram (ECG), biochemical testing, invasive and noninvasive imaging, and pathological evaluation.

Acute myocardial infarction is classified on the basis of the presence or absence of ST-segment elevation on the ECG and is further classified into six types.

Thygesen K, et al. Third universal definition of myocardial infarction. JACC 2012; 60:1581

Page 4: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

Acute Myocardial Infarction: Six Types

• Type 1: AMI due to coronary atherothrombosis • Type 2: AMI due to a supply–demand mismatch that is not the result of acute

atherothrombosis • Type 3: AMI causing sudden death without the opportunity for biomarker or

ECG confirmation • Type 4a: AMI related to a percutaneous coronary intervention (PCI) • Type 4b: AMI related to thrombosis of a coronary stent • Type 5: AMI related to coronary artery bypass grafting (CABG)This presentation will focus on the initial presentation and in-hospital management of type 1 acute myocardial infarction.

Thygesen K, et al. Third universal definition of myocardial infarction. JACC 2012; 60:1581

Page 5: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

The Changing Epidemiology of AMI• Since 1987, the adjusted incidence rate of hospitalization for AMI or fatal

coronary artery disease (CAD) in the United States has declined by 4 to 5% per year.

• Still, ≈550,000 first and ≈200,000 recurrent AMI’s occur annually.• Globally, CAD has become the leading contributor to the burden of disease

based on disability-adjusted life-years lost.• However, the global burden of cardiovascular disease (CVD) and AMI has

shifted to low- and middle-income countries, where more than 80% of deaths from CVD worldwide now occur.

• Globally, risk factor burden is directly related to income but inversely to rates of AMI. This paradox may be explained by the greater use of revascularization and preventive measures in high-income countries.

Mozaffarian D, et al. Heart disease and stroke statistics — 2016 update. Circulation 2016; 133(4):e38; Yusuf S, et-al. NEJM 2014; 371:818; Murray CJ et-al. Lancet 2015; 386:2145;

Page 6: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

Pathobiological Features of AMI

• The usual initiating mechanism for AMI is rupture or erosion of a vulnerable, lipid-laden, atherosclerotic coronary plaque.

• With more common and effective lipid-lowering therapy, plaque erosion is playing an increasing role.

• This results in exposure of circulating blood to highly thrombogenic core and matrix materials in the plaque, initiating an intraluminal thrombus.

• A totally occluding thrombus typically leads to STEMI. Partial occlusion, or occlusion in the presence of collateral circulation, results in non-STEMI or unstable angina.

• Approximately 10% of AMI cases are recognized to occur without critical epicardial CAD and are due to various other underlying mechanisms (e.g., microvascular disease and endothelial dysfunction).

Libby P. NEJM 2013; 368:2004; Libby P, et-al. Circ Res 2016; 118:531.

Page 7: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

Anderson JL, Morrow DA. Acute Myocardial Infarction. NEJM 2017; 376:2053

STEMI and NSTE-ACS:Pathology, ECG, Biomarkers, and Classification

Page 8: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

Acute Coronary Syndromes

Hospitalizations in the United States

1.19 million

hospital admissions

UA/NSTEMI STEMI

0.81 million

admissions per year

0.38 million

admissions per year

NSTEMI, non–ST-segment elevation myocardial infarction; STEMI, ST-segment elevation myocardial infarction; UA, unstable angina.Roger VL, et al. Circulation. 2012;51:210-247.

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Risk Factors for Coronary Artery Disease (CAD) and AMI

• The lifetime risk for CAD varies dramatically depending on 7 well-known risk factors (age, gender, lipid profile, blood pressure, diabetes, smoking, race).

• When all modifiable risk factors are optimal, the lifetime risk for a 45 year-old is <5%; with ≥2 major risk factors, it is 50% for men and 31% for women.

• Specific to AMI, the global INTERHEART Study identified 9 risk factors (smoking, lipids, hypertension, diabetes, obesity, diet, physical activity, alcohol consumption, and psychosocial factors) that account for over 90% of the population attributable risk of AMI.

• These AMI risk factors are the same in almost every geographic region and racial/ethnic group worldwide and are similar for men and women.

• Approximately 40% of CAD risk is genetic, and many genetic risk markers have been identified. The genetic contribution specific to AMI is less clear, and few genetic variants have been identified that predispose to precipitation of AMI.

Berry JD, et-al. NEJM 2012; 366:321; Yusuf S, et-al. Lancet 2004; 364:937, 964; Nikpay M, et-al. Nat Genet 2015; 47:1121; Reilly MP, et-al. Lancet 2011; 377:383.

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Initial Medical Presentation and Evaluation

• Patients with AMI may present with typical ischemic-type chest discomfort or with atypical discomfort, dyspnea, nausea, unexplained weakness, or a combination of symptoms.

• If AMI is suspected, the patient should be referred immediately to an emergency department (ED). Transport by ambulance is recommended.

• A 12-lead ECG is obtained with a goal of within 10 minutes of ED arrival and evaluated for ischemic changes, and blood is sent for cardiac troponin and other tests.

• On the basis of the history and ECG, rapid diagnostic triage is performed, addressing the first of 6 key assessment and management tasks/decisions.

O’Gara PT, et-al. JACC 2013; 61:e78; Amsterdam EA, et-al. JACC 2014; 64:e139

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Prehospital Care

• Goals: Rapid assessment, initiation of treatment, transport to hospital • Where possible, perform in-field ECG by EMS, communicate STEMI diagnosis

to receiving hospital, and transport to a hospital capable of primary percutaneous coronary intervention (PCI).

• This results in more rapid PCI and superior outcomes.• Direct admission to the cath lab, bypassing the ED, results in even more rapid

PCI at the cost of a higher false positive rate.• Prehospital P2Y12-inhibitor administration is safe but did not improve pre-PCI

coronary perfusion (ATLANTIC).• Prehospital therapeutic hypothermia after cardiac arrest does not improve

outcomes at discharge versus in-hospital cooling (2 trials).

Circulation 2008; 118: 1066; JACC 2009; 53: 161. Circulation 2013; 128: 352; NEJM 2014; 371: 1016; JAMA 2014; 311:45

Page 12: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

Initial Medical Presentation and Evaluation

• Patients with AMI may present with typical ischemic-type chest discomfort or with atypical discomfort, dyspnea, nausea, unexplained weakness, or a combination of symptoms.

• If AMI is suspected, the patient should be referred immediately to an emergency department (ED). Transport by ambulance is recommended.

• A 12-lead ECG is obtained with a goal of within 10 minutes of ED arrival and evaluated for ischemic changes, and blood is sent for cardiac troponin and other tests.

• On the basis of the history and ECG, rapid diagnostic triage is performed, addressing the first of 6 key assessment and management tasks/decisions.

O’Gara PT, et-al. JACC 2013; 61:e78; Amsterdam EA, et-al. JACC 2014; 64:e139

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Six Initial Assessment and Management Tasks/Decisions in Patients with Possible Acute Coronary Syndromes (ACS)

1. Triage to an ACS pathway: STEMI, non-STEMI, possible or probable unstable angina, or non-ischemic disorder, based on history, exam, ECG, and cardiac troponin results.

2. Assess risk of CV death or progressive/recurrent ischemic injury, based on history, exam, ECG, troponin. A validated risk score can be useful (TIMI, GRACE).

3. Initiate general care: limit activity; initiate aspirin, nitroglycerin, and a statin; consider oxygen, a beta-blocker, and/or morphine.

4. Choose an invasive or non-invasive (ischemia-guided) strategy, based on risk and patient preference.

5. Select a second antiplatelet agent added to aspirin (P2Y12 or GP IIb/IIIa inhibitor), based on thrombotic and bleeding risk, timing of coronary angiography, and likelihood of surgical revascularization.

6. Choose an anticoagulant agent (unfractionated heparin, low molecular weight heparin, fondaparinux, or bivalirudin) based on initial management strategy (invasive or non-invasive), timing of interventions, and bleeding risk.

Anderson JL, Morrow DA. Acute Myocardial Infarction. NEJM 2017; 376:2053

Page 14: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

Key Updates in 2014 Non-STEMI Guidelines

1. CK-MB is no longer recommended.

2. Troponin is the biomarker of choice (I or T).

3. MI diagnosis is based on troponin rise-fall.

4. Supplemental oxygen use is limited.

5. High-intensity dose statin should be given to all.

6. Ticagrelor, prasugrel are preferred over clopidogrel.

7. Invasive strategy timing is stratified into 3 groups.

Amsterdam EA, et-al. JACC 2014; 64:e139

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ACC/AHA Early Diagnosis and Risk

Stratification Guidelines for NSTE-ACS

Perform rapid determination of likelihood of ACS, including a 12-lead ECG within 10 min of arrival at an ED.

Perform serial ECGs at 15- to 30-min intervals during the first hour in symptomatic patients with initial non-diagnostic ECG.

Measure cardiac troponin (cTnI or cTnT) in all patients with symptoms consistent with ACS.

Measure serial cardiac troponin I or T at presentation and 3-6 hours after symptom onset in all patients with symptoms consistent with ACS to identify a rising and/or falling pattern.

Use risk scores (TIMI, GRACE) to assess prognosis in patients with NSTE-ACS

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

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

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

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

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

Amsterdam EA, et-al. JACC 2014; 64:e139

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Timing of Release of Various

Biomarkers After Acute MI

Amsterdam EA, et-al. JACC 2014; 64:e139

Page 17: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

Troponin-I Testing at Intermountain Healthcare

for Probable or Possible NSTE-ACS

Page 18: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

Non-ACS Causes of Elevated Troponin

• Heart failure

• Shock: septic, hypovolemic, cardiogenic

• Injury: cardiac contusion, surgery, ablation, shock

• Inflammation: myocarditis, pericarditis

• Cardiomyopathies: infiltrative, stress, hypertensive,

hypertrophic

• Aortic diseases: aortic dissection, aortic stenosis

• Tachycardia, cardioversion

• Pulmonary: embolism/hypertension, respiratory failure

• Neurologic: stroke, intracranial hemorrhage

• Renal failureThygesen K, et al. Third universal definition of

myocardial infarction. JACC 2012; 60:1581

Page 19: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

TIMI and GRACE Risk Scores

TIMI GRACE

Histo

ry

AgeHypertensionDiabetesSmoking↑ CholesterolFamily historyHistory of CAD

Age

Presen

tation

Severe anginaAspirin within 7 daysElevated markersST-segment deviation

Heart rateSystolic BPElevated creatinineHeart failureCardiac arrestElevated markersST-segment deviation

Antman EM et al. JAMA. 2000;284:835-842. Eagle KA et al. JAMA. 2004;291:2727-2733.

GRACE = Global Registry of Acute Coronary Events; TIMI = Thrombolysis in Myocardial Infarction

Page 20: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

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TIMI Risk Score1. Age ≥65 y*

2. ≥3 CAD risk factors (high

cholesterol, family history,

hypertension, diabetes,

smoking)*

3. Prior coronary stenosis ≥50%

4. Aspirin in last 7 days

5. ≥2 anginal events ≤24 h

6. ST-segment deviation*

7. Elevated cardiac markers*

(Troponin or CK-MB)

Antman EM, et al. JAMA. 2000;284(7):835-842.

Number of Predictors

0

5

10

15

20

25

30

35

40

45

0/1 2 3 4 5 6/7

% D

eath

/ M

I / U

rgen

t R

evasc a

t 14 d

Page 21: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

GRACE Risk Model Nomogram

Page 22: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

Troponin Levels Predict Risk of Mortality in NSTE-ACS

Antman EM et al. N Engl J Med. 1996;335:1342-1949.

1.01.7

3.43.7

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)

Page 23: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

Emergency Department and General Hospital Care for NSTE-ACS*1) Put at bedrest with continuous ECG monitoring.

2) Treat myocardial supply–demand mismatch

• Oxygen: Administer supplemental oxygen only if oxygen saturation <90% (2 older trials and 1 just completed).

• Analgesics: Consider IV morphine (1 to 5 mg; repeat prn in 5 to 30 min) only for persistent ischemic pain.

• Nitrates: Sublingual nitroglycerin for ischemic pain (0.3 to 0.4 mg; may repeat in 5 min. time 2, as needed); give IV nitroglycerin for persistent ischemia, heart failure, or hypertension.

• Beta-blockers (BB): Start an oral BB in the first 24 hours if no heart failure, shock, or other contraindication.

• Calcium-channel blockers (CCB): Reserve a non-dihydropyridine CCB for persistent ischemia when BB are not successful, are contraindicated, or have unacceptable side effects.

3) Treat coronary thrombus

• Antiplatelet therapy: Administer aspirin (initially, 162 to 325 mg; then 81 to 325 mg daily) and a P2Y12 inhibitor.

• Anticoagulant therapy: Administer an IV anticoagulant to all patients, regardless of treatment strategy.

4) Treat unstable atheroma or AMI progression

• Statin: Initiate/continue high-intensity statin (40-80 mg atorvastatin or 20-40 mg rosuvastatin on admission, daily)

• ACE inhibitor: Start in all patients with LVEF <0.40, hypertension, diabetes, or stable chronic kidney disease; ACEI also is reasonable in other ACS patients.

Amsterdam EA, et-al. JACC 2014; 64:e139*STEMI is generally similar

Page 24: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

Considerations for Choice of NSTE-ACS Strategy

Immediate invasive Refractory angina

strategy Signs/symptoms of HF, new/worsening mitral regurgitation

(within 2 h) Hemodynamic instability

Recurrent angina/ischemia at rest or low-level activity

_____________________ Sustained VT or VF________________________________

Early invasive strategy None of above, but GRACE risk score >140

(within 24 h) Temporal change in troponin

_____________________ New or presumably new ST depression________________

Delayed invasive None of the above but diabetes mellitus

strategy Renal insufficiency (GFR <60 ml/min/1.73 sq-m)

(within 25-72 h) Reduced LV systolic function (EF<0.40)

Early post-infarction angina

PCI within 6 months

Prior CABG

_____________________ TIMI score >=2; GRACE score 109-140_______________

Ischemia-guided Low-risk score (e.g., TIMI 0/1, GRACE <109)

strategy Low-risk, troponin-negative females

_____________________ Patient/clinician preference and no high-risk features_____

2014 AHA/ACC NSTE-ACS Guideline: Amsterdam EA, et-al. JACC 2014; 64:e139

AmstPatientl. JncianACC 2014; 64:eno9

Page 25: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

*Low/intermediate risk=GRACE score <140

High risk=GRACE score ≥140

Early: Within 24 h (mean, 15 h); Delayed: After 36 h (mean, 50 h)

TIMACS: Timing of PCI in NSTE-ACS Rates of death, MI, or stroke within 6 mo by GRACE score:

HR (95% CI), early vs delayed invasive strategy

Mehta SR et al. N Engl J Med. 2009;310:2165-2175.

EARLY

(%)

DELAYED

(%)

Hazard Ratio

(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

Page 26: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

Primary Therapeutic Strategy for STEMI: Emergent Reperfusion

*Patients with cardiogenic shock or severe heart failure initially seen at a non–PCI-capable hospital should be transferred for cardiac

catheterization and revascularization as soon as possible, irrespective of time delay from MI onset (Class I, LOE: B). †Angiography and

revascularization should not be performed within the first 2 to 3 hours after administration of fibrinolytic therapy.

O’Gara PT, et-al. JACC 2013; 61:e78

Page 27: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

Evolution in Management of AMI in the Catheterization Lab

• Increased, routine use of current generation drug eluting stents

• Cobalt chromium everolimus-eluting stents showed reduced rates of cardiac death, AMI, and stent thrombosis, c/w bare-metal stents in network analysis.

• PCI of non-culprit stenoses at time of primary PCI, previously contraindicated, now may be considered either at the time of primary PCI in hemodynamically stable patients or as a staged procedure (ACC–AHA class IIb, LOE B)

• In 2015 systematic review of 5 trials (N=1568 patients), lower relative risks (RR) of repeat revascularization (0.36 [0.27, 0.48]) and nonfatal MI (0.58 [0.36, 0.92]); uncertain effects on death (RR 0.82 [0.53, 1.26])

• Manual thrombus aspiration, previously recommended, now not indicated routinely during PCI, and selective use viewed as poorly founded (ACC–AHA class IIb, LOE C)

• In 2015 meta-analysis of 17 trials (N=20,960 patients) no significant benefit for death or reinfarction (hazard ratio 0.90; P = 0.11).

Palmerini T, et-al. JACC 2013; 62:496; Spencer FA, et-al. Am Heart J 2015; 170:1133; Levine GN, et-al. JACC 2016; 67:1235; Elgendy IY, et-al. Circ Cardiovasc Interv 2015; 8:e002258

Page 28: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

Evolution in Management of AMI in the Cath Lab (cont.)

• Radial artery access has increased and now is preferred.• Femoral artery access is associated with a high rate of access site bleeding, especially with STEMI.

• In a 2013 meta-analysis of 12 randomized STEMI trials, radial access was associated with lower rates of access site bleeding (2.1% vs. 5.6%), major bleeding (1.4% vs. 2.9%), and death (2.7% vs. 4.7%). Procedure time was 2 minutes longer.

• In the most recent (2015) and largest trial (N=8,404 STEMI or non-STEMI patients), radial access was associated with a reduced rate of adverse clinical events at 30 days, driven by decreases in deaths and major bleeding events, and it was beneficial in both types of AMI.

• A challenge to rapid adoption of the radial access approach in general practice is overcoming the learning curve for achieving the outcomes observed in clinical trials

34

Karrowni W, et-al. JACC Cardiovasc Interv 2013; 6:814; Valgimigli M, et-al. Lancet 2015; 385:2465; Hinohara TT, et-al. Prog Cardiovasc Dis; 58:241.

Page 29: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

A loading dose of a P2Y12 receptor inhibitor

(clopidogrel, prasugrel, or ticagrelor) should be

given before the procedure in patients undergoing

PCI with stenting.

It is reasonable to use ticagrelor in preference to

clopidogrel for P2Y12 treatment in patients with

NSTE-ACS who undergo an early invasive or

ischemia-guided strategy.

It is reasonable to choose prasugrel over

clopidogrel in NSTE-ACS patients who undergo PCI

and are not at high risk of bleeding.

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

P2Y12 Inhibitors in NSTE-ACS* with PCI/Stents

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

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

2014 AHA/ACC NSTE-ACS Guideline: Amsterdam EA, et-al. JACC 2014; 64:e139

*STEMI is similar

Page 30: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

PLATO: Ticagrelor vs. Clopidogel

in STEMI and Non-STE-ACS

No. at risk

Clopidogrel

Ticagrelor

9,291

9,333

8,521

8,628

8,362

8,460

8,124

Days after randomisation

6,743

6,743

5,096

5,161

4,047

4,147

0 60 120 180 240 300 360

12

11

10

9

8

7

6

5

4

3

2

1

0

13

CV

death

, M

I, o

r C

VA

in

cid

en

ce (

%)

9.8

11.7

8,219

HR 0.84 (95% CI 0.77–0.92), p=0.0003

Clopidogrel

Ticagrelor

K-M = Kaplan-Meier; HR = hazard ratio; CI = confidence interval NEJM 2009; 361:1045

Page 31: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

No. at risk

Clopidogrel

Ticagrelor

9,291

9,333

8,560

8,678

8,405

8,520

8,177

Days after randomisation

6,703

6,796

5,136

5,210

4,109

4,191

0 60 120 180 240 300 360

6

5

4

3

2

1

0

7

Cu

mu

lati

ve i

ncid

en

ce (

%)

Clopidogrel

Ticagrelor

5.8

6.9

8,279

HR 0.84 (95% CI 0.75–0.95), p=0.005

0 60 120 180 240 300 360

6

4

3

2

1

0

Clopidogrel

Ticagrelor

4.0

5.1

HR 0.79 (95% CI 0.69–0.91), p=0.001

7

5

9,291

9,333

8,865

8,294

8,780

8,822

8,589

Days after randomisation

7079

7119

5,441

5,482

4,364

4,4198,626

Myocardial infarction Cardiovascular death

Cu

mu

lati

ve i

ncid

en

ce (

%)

PLATO: Secondary efficacy endpoints

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Prasugrel vs Clopidogrel for NSTE-ACS and STEMI:

TRITON-TIMI 38 Primary ResultsCV Death, MI, Stroke

0

5

10

15

0 30 60 90 180 270 360 450

HR 0.81

P=.0004Prasugrel

Clopidogrel

HR 0.80

P=.0003

HR 0.77

P=.0001

Days

Pri

mary

En

d P

oin

t, %

12.1 (781)

9.9 (643)

NNT=46

ITT=13,608

Adapted from Wiviott SD, et al. N Engl J Med. 2007;357(20):2001-2015.

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3333

TRITON-TIMI 38: Net Clinical Benefit

Bleeding Risk SubgroupsPost hoc analysis

OVERALL

≥60 kg

<60 kg

<75

≥75

No

Yes

0.5 1 2

Prior

Stroke / TIA

Age

Wgt

Risk (%)

+ 37

-16

-1

-16

+3

-14

-13

Prasugrel Better Clopidogrel BetterHR

Pint = .006

Pint = .18

Pint = .36

Wiviott SD, et al. N Engl J Med. 2007;357(20):2001-2015.

Page 34: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

Anticoagulant Therapy in Acute Coronary Syndromes

• An IV anticoagulant agent is recommended for all patients with an ACS: i.e.,

unfractionated heparin (UFH), enoxaparin, bivalirudin, or fondaparinux (ACC-

AHA Class I, LOE A)

• In STEMI, UFH or bivalirudin are usually preferred.

• Fondaparinux alone is insufficient to support to PCI but is useful with a

noninvasive strategy, especially if bleeding risk is high.

• Enoxaparin, a low molecular weight heparin, is somewhat more effective than

UFH in patients who are treated with a noninvasive strategy.

• During noninvasive management, anticoagulants are given for at least 2 days,

or for the duration of hospitalization, up to 8 days, or until PCI is performed.

• Anticoagulants are typically discontinued after uncomplicated PCI.

O’Gara PT, et-al. JACC 2013; 61:e78; Amsterdam EA, et-al. JACC 2014; 64:e139

Page 35: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

Combined Oral Anticoagulant and Antiplatelet Therapy

• Of AMI patients, 5-10% undergoing PCI have an indication for triple antithrombotic therapy (i.e., atrial fibrillation, mechanical heart valve, venous thromboembolism, or hypercoagulable disorder). Most commonly, this is with aspirin, clopidogrel, and warfarin.

• Guideline expert opinion states that the duration of triple therapy be as short as possible and intensity as low as possible, given an increased bleeding risk.

• Recently, 2 trials have suggested improved evidence-based treatment options for these patients, i.e., with clopidogrel and a Vitamin K antagonist without aspirin (WOEST; 28% with ACS) or with low dose rivaroxaban and a P2Y12-inhibitor, with or without aspirin (PIONEER-AF PCI; 50% with ACS).

DeWilde WJ, et-al. Lancet 2013; 381:1107; Gibson CM, et-al. NEJM 2016; 375:2423.

Page 36: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

WOEST—Primary and Secondary Endpoints

DeWilde WJ, et-al. Lancet 2013

Page 37: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

Patients With Atrial Fibrillation Undergoing

Coronary Stent Placement: PIONEER AF-PCI

• Primary endpoint: TIMI major + minor + bleeding requiring medical attention

• Secondary endpoint: CV death, MI, and stroke (Ischemic, Hemorrhagic, or Uncertain Origin)

*Rivaroxaban dosed at 10 mg once daily in patients with CrCl of 30 to <50 mL/min.

†Alternative P2Y12 inhibitors: 10 mg once-daily prasugrel or 90 mg twice-daily ticagrelor.

‡Low-dose aspirin (75-100 mg/d). ∆ Open label VKA

2100

patients

with NVAF

Coronary

stenting

No prior

stroke/TIA,

GI bleeding,

Hb<10,

CrCl<30

R

A

N

D

O

M

I

Z

E

1,6, or 12 months

Rivaroxaban 15 mg qd*

Clopidogrel 75 mg qd†

Rivaroxaban 15mg QD

Aspirin 75-100 mg qd

Rivaroxaban 2.5 mg bid

Clopidogrel 75 mg qd†

Aspirin 75-100 mg qd‡

VKA∆(target INR 2.0-3.0)

Aspirin 75-100 mg qd

VKA∆ (target INR 2.0-3.0)

Clopidogrel 75 mg qd†

Aspirin 75-100 mg qd

≤72

hours

After

Sheath

removal

1,6, or 12 months

End oftreatment12 months

WOEST

Like

ATLAS

Like

Triple

Therapy

Gibson et al. AHA 2016

Pre randomization MD Choice

Pre randomization MD Choice

Page 38: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

Kaplan-Meier Estimates of First Occurrence of Clinically Significant Bleeding Events

TIM

I M

ajo

r, T

IMI M

ino

r, o

r B

leed

ing

Req

uir

ing

Med

ical A

tten

tio

n (

%)

DaysNo. at risk

VKA + DAPT

26.7%

Treatment-emergent period: period starting after the first study drug administration following randomization and ending 2 days after stop of study drug.

Clinically significant bleeding is the composite of TIMI major, TIMI minor, and BRMA.

Hazard ratios as compared to the VKA group are based on the (stratified, only for Overall, 2.5 mg BID/15 mg QD comparing VKA) Cox proportional hazards model.

Log-Rank P-values as compared to VKA group are based on the (stratified, only for Overall, 2.5 mg BID/15 mg QD comparing VKA) two-sided log rank test. Gibson et al. AHA 2016

VKA + DAPT

Riva + DAPT

18.0%

p<0.00018

HR = 0.63 (95% CI 0.50-0.80)

ARR = 8.7

NNT = 12

VKA + DAPT

Riva + P2Y12

16.8%

p<0.000013

HR = 0.59 (95% CI 0.47-0.76)

ARR = 9.9

NNT = 11

Riva + P2Y12

VKA + DAPT

Riva + DAPT

Riva + P2Y12 v. VKA + DAPT

HR=0.59 (95% CI: 0.47-0.76)

p <0.000013

ARR=9.9

NNT=11

Riva + DAPT v. VKA + DAPT

HR=0.63 (95% CI: 0.50-0.80)

p <0.00018

ARR=8.7

NNT=12

Riva + P2Y12

Riva + DAPT

VKA + DAPT

694

704

695

648

662

635

633

640

607

621

628

579

590

596

543

562

570

514

430

457

408

Page 39: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

Kaplan-Meier Estimates of First Occurrence of CV Death, MI or Stroke

Card

iovascu

lar

Death

, M

yo

card

ial

Infa

rcti

on

, o

r S

tro

ke (

%)

Days

Riva + P2Y12

Riva + DAPT

VKA + DAPT

694

704

695

648

662

635

633

640

607

621

628

579

590

596

543

562

570

514

430

457

408

VKA + DAPT

Riva + DAPT

Riva + P2Y12

Riva + P2Y12 v. VKA + DAPT

HR=1.08 (95% CI: 0.69-1.68)

p=0.750

Riva + DAPT v. VKA + DAPT

HR=0.93 (95% CI: 0.59-1.48)

p=0.765

6.5%

5.6%

6.0%

Treatment-emergent period: period starting after the first study drug administration following randomization and ending 2 days after stop of study drug.

Composite of adverse CV events is composite of CV death, MI, and stroke.

Hazard ratios as compared to VKA group are based on the (stratified, only for the Overall, 2.5 mg BID/15 mg QD comparing VKA) Cox proportional hazards model.

Log-Rank P-values as compared to the VKA group are based on the (stratified, only for Overall, 2.5 mg BID/115 mg QD comparing VKA) two-sided log rank test.

6 Subjects were excluded from all efficacy analyses because of violations in Good Clinical Practice guidelines

No. at risk

Gibson et al. AHA 2016

Page 40: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

Complications of AMI

Rates of major complications of AMI have declined dramatically with early reperfusion and current medical therapy. Nevertheless, they are a leading cause of death and disability and deserve careful consideration.

• Recurrent chest pain: ischemia, MI extension, MI expansion, pericarditis

• Arrhythmias: early and late (>48 h) VT/VF (6%), bradycardias, high grade AV block (3.5%), atrial fibrillation (5-10%)

• Mechanical complications (1%): acute mitral regurgitation (papillary muscle dysfunction), ventricular septal defect, free wall rupture, LV aneurysm

• Heart failure (18%) and cardiogenic shock (6-10%)

Anderson JL, Morrow DA. Acute Myocardial Infarction. NEJM 2017; 376:2053

Page 41: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

Post-hospital systems of care designed to prevent

hospital readmissions should be used to facilitate

the transition to effective, coordinated outpatient

care for all patients with NSTE-ACS.

An evidence-based plan of care that promotes

medication adherence, timely follow-up,

appropriate dietary and physical activities, and

compliance with secondary prevention should be

provided to patients with NSTE-ACS.

Annual influenza vaccination for all patients.

.

2014 AHA/ACC NSTE-MI Guidelines

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

General Plan of Outpatient Care for Patients with NSTE-ACS*

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

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

: : Amsterdam EA, et-al. JACC 2014; 64:e139

*STEMI is similar

Page 42: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

Secondary Prevention*

Recommendations COR LOE

Lipid management with

lifestyle modification and

lipid-lowering therapy

Lifestyle modification I B

Statin therapy – mod/high intensity I A

Beta-blocker therapyFor 3 yrs in pts with normal LVF

All pts with EF <40, HF, prior MII B A

RAAS blocker therapyACEI if HTN, DM, EF <40, CKD

Use ARBs if intolerant of ACEIsI A

Blood pressure control (with a

blood pressure goal of

<140/90 mm Hg)

Lifestyle modification I B

Pharmacotherapy I A

Diabetes management (eg, lifestyle modification and pharmacotherapy)

coordinated with the patient’s primary care physician and/or endocrinologist. I C

Complete smoking cessation I A

Amsterdam EA, et-al. JACC 2014; 64:e139

In addition, referral to a cardiac rehabilitation program (IB). *Comprehensive secondary prevention recommendations in the ACC/AHA Secondary Prevention and Risk Reduction 2011 and 2013 Updates and 2012 SIHD Guidelines

LVF=Left Ventricular Function; EF=Ejection Fraction; CKD=Chronic Kidney Disease; ARB=Angiotensin Receptor Blocker; ACEI=Angiotensin-Converting Enzyme Inhibitor; HTN=Hypertension; RAAS=Renin-Angiotensin-Aldosterone System

Page 43: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

Performance Matters!Association Between Hospital Guideline

Adherence and In-hospital Mortality in CRUSADE

Adapted from Peterson ED, et al. JAMA. 2006;295(16):1912-1920.

NSTE ACS = non–ST-segment elevation ACS.

8

7

6

5

4

3

2

1

01 2 3 4

In-H

os

pit

al M

ort

ali

ty,

%

Hospital Composite Guideline

Adherence Quartiles

NSTE ACS

CRUSADE = Can Rapid

Risk Stratification of

Unstable Angina Patients

Suppress Adverse

Outcomes With Early

Implementation of the

ACC/AHA Guidelines.

Page 44: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

PERFORMANCE MATTERS: Impact of Adherence to Evidence-based Therapies on

6-mo Survival in the GRACE Registry Cohort*

OR = odds ratio

*Registry of patients with ACS

Chew DP et al. Heart. 2010;96:1201-1206.

0.80 (0.52-1.26)

0.74 (0.48-1.13)

0.59 (0.39-0.90)

0.51 (0.33-0.78)

0.40 (0.26-0.62)

0.27 (0.16-0.44)

0.31 (0.17-0.57)

NUMBER OF THERAPIES

(vs 0 or 1 therapy)

2 therapies

3 therapies

4 therapies

5 therapies

6 therapies

7 therapies

8 therapies

OR

(95% CI)

0 0.5 1 1.5 2

OR

Page 45: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

Changing Outcomes in

Acute Coronary Syndromes*

15

7.85.5

4.1

30

13.3

9.1

4.6

0

5

10

15

20

25

30

35

1970s 1999 2005 2013

NSTE-ACS STEMI

% 6

-mo M

ort

alit

y

*GRACE Registry plus historical data; AJC 118:1105; BMC Cardiovasc Disorders 2017; 17:139

Page 46: Acute Myocardial Infarction - … Myocardial Infarction: Definition & Classification Acute myocardial infarction is an event of myocardial necrosis caused by an unstable ischemic syndrome.

Thank you!