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
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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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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
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
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
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
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;
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.
Anderson JL, Morrow DA. Acute Myocardial Infarction. NEJM 2017; 376:2053
STEMI and NSTE-ACS:Pathology, ECG, Biomarkers, and Classification
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.
• 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.
• 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.
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
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
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
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
20
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
GRACE Risk Model Nomogram
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)
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
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
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
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
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).
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
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).
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
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
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%)
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