Cleveland Clinic Board Review Course
Management of Acute Myocardial Infarction A. Michael Lincoff, M.D. Vice Chairman for Clinical Research, Lerner Research Institute Director, Cleveland Clinic Coordinating Center for Clinical Research Vice Chairman, Department of Cardiovascular Medicine Professor of Medicine
AML
Spectrum of Acute Coronary Syndrome
Antman et al. ACC AHA ST Elevation MI Guidelines 2004.
AML
ACC-AHA Guidelines Class of Recommendation I IIa IIb III Intervention is useful and effective Evidence supportive; awaiting confirming data Evidence conflicts/opinions differ; neutral statement Intervention is not useful/effective and may be harmful
AML
Management of Acute MI Initial evaluation Reperfusion therapy Adjunctive antithrombotic therapy Adjunctive medical therapy Complications
AML
Management of Acute MI Initial evaluation Reperfusion therapy Adjunctive antithrombotic therapy Adjunctive medical therapy Complications
AML
ACC-AHA STEMI Guidelines Initial Management of Acute MI I IIa IIb III Targeted history should be performed. Targeted physical exam should be performed to assess extent and complications Neurologic examination should be performed to evaluate for prior or acute stroke prior to lysis 12-lead ECG should be performed and shown to experienced physician within 10 min of arrival
Antman EM. J Am Coll Cardiol 2008;51:210-47.
AML
Initial Evaluation of Acute MI Targeted History Prior coronary ischemia – stable or unstable
Prior MI or coronary revascularization
Description of chest discomfort, associated symptoms
HTN, DM
Possibility of aortic dissection
Neurologic symptoms – TIA or CVA
Risk factors for bleeding
AML
Initial Evaluation of Acute MI Targeted Physical Examination
Airway, breathing, circulation
Vital signs, general observation
Systemic hypoperfusion
JVD
Pulmonary – CHF
Cardiac – murmurs, gallops
Pulses
Signs of stroke
AML
Acute MI - Risk Stratification The GUSTO Pyramid - 30 Day Mortality Model HX CV Disease (0.4%)
HTN (0.6%) Prior CABG (0.8%)
Accel tt-PA -PA (0.8%) Smoker (0.8%) Weight (0.8%) Diabetes (1%) Time -to-Rx (1%) Time-to-Rx Age x Killip (1.3%)
Height (1.1%)
MI Location (6%)
Prior MI (3%)
Heart Rate (12%)
Killip Class (15%)
Systolic Blood Pressure (24%)
Age (31%) Lee et al. Circulation 1995;91:1659 -1668 1995;91:1659-1668
AML
Management of Acute MI Initial evaluation Reperfusion therapy Adjunctive antithrombotic therapy Adjunctive medical therapy Complications
AML
Fibrinolytics: Placebo-Controlled Trials Meta-Analysis Agent
Trial
Streptokinase GISSI
Anistreplase Alteplase
Deaths/Patients Active Control 495/4865
623/4878
ISAM
50/842
61/868
ISIS-2
471/5350
648/5360
AIMS
32/502
61/502
182/2516
245/2495
ASSET
Overall - Any Lytic Pts < 6 hrs
Odds Ratio (& 95% CI)
11.6%
23% 6
II
16% 18
II
30% 5
II
50% 16
II
1230/14075 1638/14103
8.7%
Odds Reduction (& 95% CI)
0
II
28% 9
II
27% 3
Lytic Better
Granger et al. Drugs 1992;44:293-325.
1
Lytic Worse
2
AML
Fibrinolysis for Acute MI Electrocardiographic Criteria for Therapy Pooled Analysis of Randomized Trials EKG BBB
Odds Ratio & 95% CI
ST Anterior
Placebo Lysis
23.6%
18.7%
16.9%
13.2%
8.4%
7.5%
13.4%
10.6%
13.8%
15.2%
5.8%
5.2%
2.3%
3.0%
ST Inferior
ST Other
ST
Other Abnorm Normal 0.33
Lysis Better
1
Placebo Better
3
Fibrinolytic Therapy Trialists. Lancet 1994;343:311.
AML
Acute MI Intracranial Hemorrhage Rates Large-Scale Fibrinolytic Trials 1.4
Intracranial Hemorrhage (%) SK
1.2
tPA
rPA
TNK
1.0
0.91 0.87
0.8
0.70
0.6 0.4
nPA
0.72
1.13 0.93 0.94
0.72 0.62
0.51 0.40 0.30
0.30
0.37
0.2 0.0 GISSI-2
ISIS-3
GUSTO-1 GUSTO-2 GUSTO-3 ASSENT-2 INTIME-2
AML
Fibrinolysis in Acute MI Absolute Contraindications « Any prior intracranial hemorrhage « Intracranial neoplasm or vascular lesion (e.g. AVM) « Ischemic stroke in prior 3 months « Significant closed head or facial trauma in prior 3 months « Active bleeding or diathesis (not menses) « Suspected aortic dissection
AML
Fibrinolysis in Acute MI Relative Contraindications
Uncontrolled HTN (BP > 180/110 mm) on presentation
History of chronic, severe, uncontrolled HTN
History prior CVA beyond 3 months, dementia, or intracranial pathology not covered in absolute contraindications
Recent internal bleeding (within 2-4 wks)
Traumatic or prolonged (>10 min) CPR
Major surgery (within 3 weeks)
Noncompressible vascular punctures
Anticoagulant Rx with INR > 2-3
Pregnancy
Active peptic ulcer
AML
PCI vs Fibrinolysis for Acute MI Pooled Analysis of 23 RCTs, 7739 Patients Endpoint
Short-Term Outcome Relative Risk & 95% CI
N
Death Streptokinase Fibrin-specific
1837 5902
re-MI Streptokinase Fibrin-specific
987 5510
Stroke Streptokinase Fibrin-specific
788 5843
I I
I I
I I
0.1
PCI Better
1
Lysis Better
Keeley et al. Lancet 2003;361:13-20.
PCI
Lysis
5% 8%
10% 9%
1% 3%
10% 6%
1% 1%
2% 2%
10
AML
On-Site Lysis vs Emergency Transfer for PCI Pooled Analysis of 5 RCTs - Death, MI, or Stroke Relative Risk & 95% CI
N
Trial Maastricht
150
PRAGUE-1
200
Air-PAMI
137
PCI
N
N
N
Lysis
10.7%
18.7%
7.9%
23.2%
8.5%
13.6%
DANAMI-2
1572
N
8.0%
13.7%
PRAGUE-2
850
N
8.4%
15.2%
2909
N
8.3%
15.0%
Pooled
0.1
PCI Better
1
Lysis Better
10
Keeley et al. Lancet 2003;361:13-20 and Dalby et al. Circulation 2003;108:1809.
AML
AMI and Primary PCI - ZWOLLE Group 1791 Patients: Total Ischemic Time and Mortality 12
RR = 1.075 [1.008-1.15, p = 0.041] for each 30 min delay
1-Yr Mortality (%)
10 8 6 4 2
p 100 bpm
Reteplase (1/2 dose) + Abciximab
Tenecteplase (full dose)
Immediate transfer for PCI
Transfer only for rescue PCI
Immediate transfer for PCI
Transfer only for rescue PCI
85.6% PCI Median 1.8 hrs
30.3% PCI Median 3 hrs
84.9% PCI Median 2.8 hrs
67.4% PCI Median 33 hrs
DiMario et al. Lancet 2008;371:559.
Cantor et al. NEJM 2009;360:2705.
AML
STEMI - Triage and Transfer for PCI CARESS in AMI Trial
12
Death, re-MI, Refractory Ischemia, CHF, Shock (%) 18 17.2 16 p = 0.004 14
Death, re-MI, Refractory Ischemia (%) 10.7
10
p = 0.005 8
Major Bleeding:
6
Transfer Rescue p = 0.80
4
4.4
2.7% 2.3%
Major Bleeding:
12 10
11.0
Transfer Rescue p = 0.36
8 6
9.0% 7.4%
4
2 0
TRANSFER AMI Trial
2 Transfer for PCI
Rescue PCI
DiMario et al. Lancet 2008;371:559.
0
Transfer for PCI
Rescue PCI
Cantor et al. NEJM 2009;360:2705.
AML
ACC-AHA 2009 STEMI Update Triage and Transfer for PCI I IIa IIb III Community STEMI system of care including transfer protocols Transfer of “high risk” pts ASAP after lysis from hospitals without PCI facility to PCIcapable facility for “pharmacoinvasive” strategy Consider transfer of “non-high-risk” pts ASAP after lysis from hospitals without PCI facility to PCI-capable facility Kushner et al. ACC/AHA 2009 Focused Update of STEMI / PCI Guidelines.
AML
Management of Acute MI Initial evaluation Reperfusion therapy Adjunctive antithrombotic therapy Adjunctive medical therapy Complications
AML
Aspirin in Acute MI ISIS-2 20
35 Day Mortality (% ) ISIS-2 Collaborative Group, Lancet 1988;2:349.
15 13.2
10
10.7
10.4 8
5 0
4300
4295
4300
4292
Placebo
ASA
SK
SK + ASA
Class I, LOE A: Aspirin daily indefinitely after STEMI in all pts without true a spirin allergy. aspirin Initial dose – 165 -325 mg. Maintenance dose – 75 -162 mg. 165-325 75-162
AML
CLARITY - TIMI 28 Clopidogrel in STEMI 30 25 20 15
Death/MI/Occluded IRA (%)
Cardiac Death, re-MI, Urgent Revascularization (%) 15
Odds Ratio 0.64 (95% CI 0.53-0.76) P
