Definition of MI Dual antiplatelet therapy in secondary prevention

1. Myocardial Infarction FAQ
: Based on Current Guidelines and Evidence
Joonseok (“Joon”) Kim, M.D.
MSU Internal Medicine PGY3
February 13, 2014

2. Contents
•
•
•
•
Definition of MI
Interpretation of Troponin Elevations
MI in Critically Ill Patients
Antiplatelet Therapy in Post MI

3. CASE
• A 56-year-old man is admitted to the hospital with new-onset
substernal chest pressure. Medical history is remarkable for
hyperlipidemia. He is a cigarette smoker. His medications are aspirin
and atorvastatin.
• On physical examination, the patient is afebrile, blood pressure is
132/78 mm Hg, pulse rate is 82/min and regular, and respiration rate
is 14/min. No jugular venous distention is noted, the lungs are clear
to auscultation, no murmur or gallop is heard, and no peripheral
edema is noted.

4. CASE
• On admission, cardiac troponin I level was 1.2 ng/mL (1.2 µg/L); on
hospital day 2 it peaks at 8.4 ng/mL (8.4 µg/L). An electrocardiogram
on arrival to the emergency department demonstrated a nonspecific
ST-T wave abnormality, but no ST-segment elevation or depression.
He began receiving metoprolol, clopidogrel, and intravenous
heparin.
• Cardiac catheterization demonstrates overall preserved left
ventricular systolic function with diffuse severe disease of the distal
portion of all three major epicardial vessels. No catheter-based
intervention is performed.

5. CASE
• What do you want to do upon discharge?
A. Continue aspirin only and stop clopidogrel
B. Continue aspirin + clopidogrel therapy for 2 weeks
C. Continue aspirin + clopidogrel therapy for 1 year
D. Continue aspirin + clopidogrel therapy lifelong

6. In Reality…

7. Since 2011…
•
AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients
With Coronary and Other Atherosclerotic Vascular Disease: 2011 Update
•
ACCF 2012 Expert Consensus Document on Practical Clinical
Considerations in the Interpretation of Troponin Elevations
•
2012 ACCF/AHA Focused Update of the Guideline for the Management of
Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction
•
2012 Third Universal Definition of Myocardial Infarction
•
2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial
Infarction

9. Let‟s Go Back to Basics
What is MI?

10. Presentation
Working Dx
ECG
Cardiac
Biomarker
Final Dx
Ischemic Discomfort
Acute Coronary Syndrome
No ST Elevation
Non-ST ACS
UA
NSTEMI
ST
Elevation
Unstable Myocardial Infarction
Angina
NQMI
Qw MI
10
Libby P. Circulation 2001;104:365, Hamm CW, Bertrand M, Braunwald E, Lancet 2001; 358:1533-1538; Davies MJ. Heart 2000; 83:361366. Anderson JL, et al. J Am Coll Cardiol. 2007;50:e1-e157, Figure 1. Reprinted with permission.

11. Causes of UA/NSTEMI
• Thrombus or thromboembolism, usually arising on
disrupted, or eroded plaque
• Occlusive thrombus, usually with collateral vessels
• Subtotal occlusive thrombus on pre-existing plaque
• Distal microvascular thromboembolism from plaque-associated
thrombus
• Thromboembolism from plaque erosion
• Non–plaque-associated coronary thromboembolism
• Dynamic obstruction (coronary spasm or
vasoconstriction) of epicardial and/or microvascular
vessels
• Progressive mechanical obstruction to coronary flow
• Coronary arterial inflammation
• Secondary UA
• Coronary artery dissection
DeWood MA, et al. N Engl J Med 1986;315:417–23; Braunwald E. et al. Circulation 1998;98:2219–22; Anderson JL, et al. J Am Coll Cardiol. 2007;50:e1-e157

12. ACC/AHA

29. 10 Points to Remember from an Expert Consensus
Document on Interpretation of Troponin Elevations
• 1. Even though elevated troponin is a sensitive
and specific indication of cardiac myonecrosis,
by itself, it does not indicate a myocardial
infarction (MI) (myonecrosis due to ischemia)
or any specific etiology.
ACCF 2012 Expert Consensus Document on Practical Clinical Considerations in the Interpretation of Troponin Elevations. JACC 2012

30. 10 Points to Remember from an Expert Consensus
Document on Interpretation of Troponin Elevations
• 2. The ‘Third Universal Definition of Myocardial
Infarction’ (2012) classifies 5 types of MI: Type 1 is
termed spontaneous, related to ischemia due to a
primary coronary event (e.g., plaque rupture); Type 2 is
secondary to increased oxygen demand or decreased
supply; Type 3 is associated with sudden unexpected
cardiac death; Type 4a is associated with percutaneous
coronary intervention (PCI); Type 4b is associated with
stent thrombosis; and Type 5 is associated with coronary
artery bypass grafting (CABG) surgery.
ACCF 2012 Expert Consensus Document on Practical Clinical Considerations in the Interpretation of Troponin Elevations. JACC 2012

31. 10 Points to Remember from an Expert Consensus
Document on Interpretation of Troponin Elevations
• 3. An elevated troponin level that is
„smoldering‟ and relatively constant over an
appropriate sampling interval is more likely
to be caused by chronic diseases (e.g., heart
failure) versus ischemia.
ACCF 2012 Expert Consensus Document on Practical Clinical Considerations in the Interpretation of Troponin Elevations. JACC 2012

32. 10 Points to Remember from an Expert Consensus
Document on Interpretation of Troponin Elevations
• 4. A 20% change at 3-6 hours from the
baseline value may be suggestive of MI. That
said, there is insufficient evidence to provide
concrete guidelines on how to differentiate
between acute coronary syndrome (ACS) and
non-ACS ischemia-induced troponin elevations
without accounting for the clinical circumstances.
ACCF 2012 Expert Consensus Document on Practical Clinical Considerations in the Interpretation of Troponin Elevations. JACC 2012

33. 10 Points to Remember from an Expert Consensus
Document on Interpretation of Troponin Elevations
• 5. It is imperative to incorporate troponin testing
into global risk assessment. Those patients with
an elevated troponin and a high pretest
probability of ACS are most likely to derive
benefit from a treatment strategy that targets
coronary thrombosis.
ACCF 2012 Expert Consensus Document on Practical Clinical Considerations in the Interpretation of Troponin Elevations. JACC 2012

34. 10 Points to Remember from an Expert Consensus
Document on Interpretation of Troponin Elevations
• 9. Regardless of the etiology of troponin
elevation (or associated disease state),
troponin elevation offers incremental
prognostic value.
ACCF 2012 Expert Consensus Document on Practical Clinical Considerations in the Interpretation of Troponin Elevations. JACC 2012

35. Troponin I Levels to Predict the Risk
of Mortality in Acute Coronary Syndromes
Crude mortality rates at 42 days in patients with ACS
35
Antman EM, et al. N Engl J Med 1996;335:1342.

36. 10 Points to Remember from an Expert Consensus
Document on Interpretation of Troponin Elevations
• 10. Troponin may be a useful tool to detect
chemotherapy-associated cardiac toxicity, and
may have a role in informing the use of
treatment in those patients who develop cardiac
myonecrosis following high-dose chemotherapy.
ACCF 2012 Expert Consensus Document on Practical Clinical Considerations in the Interpretation of Troponin Elevations. JACC 2012

37. Myocardial Infarction in the ICU
• Elevations of troponin values are common in
patients in the intensive care unit and are
associated with adverse prognosis, regardless
of the underlying disease state.
Third Universal Definition of Myocardial Infarction, JACC 2012

38. Myocardial Infarction in the ICU
• Some elevations may reflect MI type 2 due to
underlying CAD and increased myocardial
oxygen demand
• Other patients may have elevated values of
cardiac biomarkers, due to myocardial injury
with necrosis induced by catecholamines or
direct toxic effect from circulating toxins
• Moreover, in some patients, MI type 1 may occur
Third Universal Definition of Myocardial Infarction, JACC 2012

39. Myocardial Infarction in the ICU
• It is often a challenge for the clinician, caring for a
critically ill patient with severe single organ or multiorgan pathology, to decide on a plan of action when the
patient has elevated cTn values.
• If and when the patient recovers from the critical
illness, clinical judgment should be employed to
decide whether—and to what extent—further
evaluation for CAD or structural heart disease is
indicated.
Third Universal Definition of Myocardial Infarction, JACC 2012

40. Antiplatelet Therapy

41. Applying Classification of
Recommendations and Level of Evidence
Class I
Class IIa
Class IIb
Class III
Benefit >>> Risk
Benefit >> Risk
Additional studies with
focused objectives
needed
Benefit ≥ Risk
Additional studies with
broad objectives
needed; Additional
registry data would be
helpful
Risk ≥ Benefit
No additional studies
needed
Procedure/ Treatment
SHOULD be
performed/
administered
should
is recommended
is indicated
is useful/effective/
beneficial
IT IS REASONABLE
to perform
procedure/administer
treatment
is reasonable
can be useful/effective/
beneficial
is probably
recommended or
indicated
Procedure/Treatment
MAY BE CONSIDERED
may/might be considered
may/might be reasonable
usefulness/effectiveness
is unknown
/unclear/uncertain or not
well established
Procedure/Treatment
should NOT be
performed/administered
SINCE IT IS NOT
HELPFUL AND MAY BE
HARMFUL
is not recommended
is not indicated
should not
is not
useful/effective/benefici
al
may be harmful
ACC/AHA Recommendations

42. Applying Classification of
Recommendations and Level of Evidence
Class I
Class IIa
Class IIb
Class III
Benefit >>> Risk
Benefit >> Risk
Additional studies with
focused objectives
needed
Benefit ≥ Risk
Additional studies with
broad objectives needed;
Additional registry data
would be helpful
Risk ≥ Benefit
No additional studies
needed
Procedure/ Treatment
SHOULD be
performed/
administered
IT IS REASONABLE to
perform
procedure/administer
treatment
Procedure/Treatment
MAY BE CONSIDERED
Procedure/Treatment
should NOT be
performed/administered
SINCE IT IS NOT
HELPFUL AND MAY
BE HARMFUL
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
ACC/AHA Recommendations

43. Aspirin Evidence: Secondary Prevention
Category
Acute MI
Acute CVA
Prior MI
Prior CVA/TIA
Other high risk
CVD
(e.g. unstable angina, heart failure)
PAD
(e.g. intermittent claudication)
High risk of embolism (e.g. Afib)
Other (e.g. DM)
All trials
% Odds Reduction
0.0
0.5
Antiplatelet better
1.0
2.0
1.5
Control better
Aspirin reduces the risk of adverse cardiovascular events
*Aspirin was the predominant antiplatelet agent studied
**Include MI, stroke, or death
Antithrombotic Trialists’ Collaboration. BMJ 2002;324:71–86

44. Aspirin Recommendation: Secondary Prevention
I IIaIIbIII
Aspirin (75-162 mg daily) if known CAD† or NSTE-ACS‡
I IIaIIbIII
Aspirin (81-325 mg daily) following PCI or fibrinolytic
therapy for a STEMI*
I IIaIIbIII
Aspirin (preferentially at 81 mg daily) following PCI for a
NSTE-ACS# or a STEMI* or fibrinolytic therapy for a
STEMI*
Smith SC Jr. et al. JACC 2011;58:2432-2446
Wright RS et al. JACC 2011;57:e215-367
O’Gara PT et al. JACC 2013;61:e78-e140

45. Aspirin Recommendation: Secondary Prevention
I IIaIIbIII
I IIaIIbIII
Aspirin (162-325 mg daily) for at least 1 month after
bare metal stent implantation (Class I, Level B), at
least 3 months after sirolimus-eluting stent
implantation (Class I, Level B), and at least 6 months
after paclitaxel-eluting stent implantation (Class I,
Level B) after which aspirin (75-162 mg daily) should
be continued indefinitely (Class I, Level A for a bare
metal stent and Class I, Level B for a drug eluting
stent)
I IIaIIbIII
Aspirin (75-162 mg daily) as the initial dose after
stent implantation in those at higher bleeding risk
King SB 3rd et al. JACC 2008;51:172-209

46. Aspirin Recommendation: Secondary Prevention
I IIaIIbIII
Aspirin (100-325 mg daily) following CABG surgery
Hillis LD et al. JACC 2011;58:e123-210

47. DAPT Recommendation: Secondary Prevention
Clopidogrel in Unstable Angina to Prevent Recurrent Events
(CURE) Trial
Rate of CV death,
myocardial infarction,
or stroke
12,562 patients with NSTE-ACS randomized to daily aspirin (75-325 mg) or clopidogrel
(300 mg load, 75 mg thereafter) plus aspirin (75-325 mg) for 9 months
Aspirin + Placebo
Aspirin + Clopidogrel
P<0.001
0
3
6
9
12
Months of Follow Up
Dual antiplatelet therapy is more efficacious in NSTE-ACS
CURE Trial Investigators. NEJM 2001;345:494-502

48. DAPT Recommendation: Secondary Prevention
Clopidogrel for the Reduction of Events during Observation
(CREDO) Trial
Risk of MI, stroke,
or death (%)
2,116 patients undergoing PCI randomized to 4 weeks of DAP* followed by aspirin (75-325
mg) monotherapy vs. persistent DAP* for 1 year
15
4 weeks of DAP*
10
1 year of DAP*
5
27% RRR, P=0.02
00
3
6
Months from Randomization
9
12
DAP therapy produces greater benefit when used for 1 year
Steinhubl S et al. JAMA 2002;288:2411-2420

49. DAPT Recommendation: Secondary Prevention
Clopidogrel and Metoprolol in Myocardial Infarction
(COMMIT) Trial
45,852 patients presenting within 24 hours of STEMI treated medically and randomized to
aspirin and clopidogrel (75 mg daily) vs. aspirin only
Death, MI, or Stroke, %
9
8
7
6
5
4
9% relative risk
reduction (P=.002)
3
0
(8.1%)
(7.5%)
8
In-Hospital Mortality, %
(10.1%)
(9.2%)
10
7
6
5
4
3
2
7% relative risk
reduction (P=.03)
1
0
0
7
14
21
28
Days Since Randomization (up to 28 days)
0
7
14
21
28
Days Since Randomization (up to 28 days)
DAPT produces greater benefit in medically managed STEMI patients
COMMIT Collaborative Group. Lancet 2005;366:1607-1621

50. DAPT Recommendation: Secondary Prevention
I IIaIIbIII
I IIaIIbIII
I IIaIIbIII
Clopidogrel (75 mg daily; Class I, Level B), prasugrel*
(10 mg daily; Class I, Level C), or ticagrelor (90 mg
twice daily; Class I, Level C) if aspirin intolerance or a
true aspirin allergy following a NSTE-ACS
Clopidogrel (75 mg daily) or ticagrelor (90 mg twice
daily) in addition to aspirin for up to 1 year following a
NSTE-ACS managed conservatively
*In PCI treated patients
Jneid H et al. JACC 2012;60:645-681

51. DAPT Recommendation: Secondary Prevention
I IIaIIbIII
Clopidogrel (75 mg daily), prasugrel (10 mg daily), or
ticagrelor (90 mg twice daily) in addition to aspirin
for 1 year following PCI for a NSTE-ACS or a STEMI
I IIaIIbIII
I IIaIIbIII
Clopidogrel (75 mg daily) in addition to aspirin for a
minimum of 14 days (Class I, Level A) and up to 1
year (Class I, Level C) following fibrinolytic therapy
for a STEMI
Jneid H et al. JACC 2012;60:645-681
O’Gara PT et al. JACC 2013;61:e78-e140

52. DAPT Recommendation: Secondary Prevention
I IIaIIbIII
If the risk of morbidity because of bleeding outweighs
the anticipated benefit afforded by a P2Y12 receptor
antagonist, earlier discontinuation should be considered
I IIaIIbIII
Continuation of a P2Y12 receptor antagonist beyond 1
year may be considered in patients undergoing drug
eluting stent placement
Kushner F et al. JACC 2009;54:2205-2241
Jneid H et al. JACC 2012;60:645-681
O’Gara PT et al. JACC 2013;61:e78-e140

53. CASE
• A 56-year-old man is admitted to the hospital with new-onset
substernal chest pressure. Medical history is remarkable for
hyperlipidemia. He is a cigarette smoker. His medications are aspirin
and atorvastatin.
• On physical examination, the patient is afebrile, blood pressure is
132/78 mm Hg, pulse rate is 82/min and regular, and respiration rate
is 14/min. No jugular venous distention is noted, the lungs are clear
to auscultation, no murmur or gallop is heard, and no peripheral
edema is noted.

54. CASE
• On admission, cardiac troponin I level was 1.2 ng/mL (1.2 µg/L); on
hospital day 2 it peaks at 8.4 ng/mL (8.4 µg/L). An electrocardiogram
on arrival to the emergency department demonstrated a nonspecific
ST-T wave abnormality, but no ST-segment elevation or depression.
He began receiving metoprolol, clopidogrel, and intravenous
heparin.
• Cardiac catheterization demonstrates overall preserved left
ventricular systolic function with diffuse severe disease of the distal
portion of all three major epicardial vessels. No catheter-based
intervention is performed.

55. Back to Initial Case…
• What do you want to do upon discharge?
A. Continue aspirin only and stop clopidogrel
B. Continue aspirin + clopidogrel therapy for 2 weeks
C. Continue aspirin + clopidogrel therapy for 1 year
D. Continue aspirin + clopidogrel therapy lifelong

56. Q&A
• Thank you for your attention