Title: ACCAHA Guidelines for the Management of Patients with Unstable Angina and NonSTSegment Elevation MI
1ACC/AHA Guidelines for the Management of Patients
with Unstable Angina and Non-ST-Segment Elevation
MI
- Published in JACC and Circulation
- September, 2000
- Revisions Released in March, 2002
Guidelines Issues for Emergency Medicine Pollack
CV, Gibler WB. Ann Emerg Med 2001
2Evidence-Based MedicineWhats the Problem?
- There is an unsettling truth about the practice
of medicine. study after study shows that few
physicians systematically apply to everyday
treatment the scientific evidence about what
works best.
Millenson, ML. Demanding Medical Excellence
Doctors and Accountability in the Information
Age. 1997
3Ischemic Heart DiseaseUnstable Angina and Acute
MI
- 12,200,000 people in the US have had an MI,
angina pectoris, or both - 5,315,000 Americans visited Emergency Departments
for chest pain in 1997 - 1,433,000 Americans hospitalized for IHD in 1996
- 225,000 died before hospital
- 1,100,000 Americans will have a new or repeat IHD
event this year
WHO 2000, NCHS 2000 AHA - 2000 Heart and Stroke
Statistical Update
4Spectrum of Acute Coronary Syndromes
Ischemic Discomfort at Rest
Presentation
No ST-Segment Elevation
ST-Segment Elevation
Emergency Department
In-Hospital
Non-Q-wave MI
Unstable Angina
Q-wave MI
(? positive cardiac biomarker)
5Participants in Updated Guidelines
6Updated GuidelinesReview Process
- Reviewers
- 3 AHA
- 1 ACP-ASIM
- 3 ACC
- 1 ESC
- 3 ACEP
- 1 STS
- 1 AAFP
- 29 Others
Original Guidelines
Literature searches
Evidence tables
Revise Guidelines draft
Final Approval by ACC and AHA
7Updated GuidelinesWeighing the Evidence
- 1994 version was starting point literature
searches added more current reports - Weight of evidence grades
- Data from many large, randomized trials
- Data from fewer, smaller randomized trials,
careful analyses of nonrandomized studies,
observational registries - Expert consensus
8Updated GuidelinesClasses of Recommendations
- Intervention is useful and effective
- Evidence conflicts/opinions differ but leans
towards efficacy - Evidence conflicts/opinions differ but leans
against efficacy - Intervention is not useful/effective and may be
harmful
9Prognosis in Unstable Angina / NSTEMI
PURSUIT trial data
10Mortality in Non-ST ? ACS Patients
WithMyocardial Infarction During Hospitalization
20
Patients with MI within 72 hours (n593)
18.3
Mortality
15
12.8 ?(P 0.0001)
10
Patients without MI within 72 hours (n8,868)
5.5
5
Days following randomization
Fintel D, ACC, 2000
11Initial Chest PainEvaluation
Symptoms Suggestive of ACS
Definite ACS
Possible ACS
() ECG Normal biomarkers
ST ?
No ST ?
Use MI Guidelines
ST-T ?s, chest pain, ? markers
Observe repeat ECG, markers at 4-8 hrs
No recurrent pain () follow-up studies
Recurrent pain () follow-up studies
Stress test ? LV function if ischemia
() test
Admit, Use Acute Ischemia Pathway
() test outpt follow-up
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18Hospital CareAnti-Thrombotic Therapy
- Immediate aspirin
- Clopidogrel, if aspirin contraindicated
- Aspirin clopidogrel for up to 1 month, if
medical therapy or PCI is planned - Heparin (IV unfractionated, LMW) with
antiplatelet agents listed above - Enoxaparin preferred over UFH unless CABG is
planned within 24 hours
19Acute Coronary Syndromes Without ST ?Evidence
for Aspirin
Cairns Lewis Theroux Wallentin Pooled
0
1.0
2.0
Favors Placebo
Favors Aspirin
Relative Risk Death or MI
20Acute Coronary Syndromes without ST ? Evidence
for Heparin Use (UFH ASA versus ASA)
Relative Risk of Death or MI
Theroux (n 243) RISC (n 399) Cohen (n
69) Cohen (n 214) Holdright (n 185) Gurfinkel
(n 143) Overall (n 1353)
2.66
6.87
P 0.06
0.5
1
1.5
2
0
ASA UFH Better
ASA Better
Oler A, JAMA 1996
21LMWH vs. UFH in Non-ST ?ACSEffect on Death, MI,
Recurrent Ischemia
Trial FRIC (Dalteparin n
1,482) FRAXIS (nadroparin n 2,357) ESSENCE (eno
xaparin n 3,171) TIMI 11B (enoxaparin n
3,910)
?
?
(p 0.032)
?
(p 0.029)
?
.75 1.0 1.5
LMWH Better
UFH Better
Braunwald E, Circulation 2000
22Hospital CareClopidogrel Therapy
- Aspirin clopidogrel, for up to 1 month
- Aspirin clopidogrel, for up to 9 months
- Withhold clopidogrel for 5-7 days for CABG
For patients managed with an early conservative
strategy, and those who are planned to
undergo early PCI
?Guidelines do not specify initial approach to
using clopidogrel when coronary anatomy
is unknown
23CURE Primary Results
14
11.4
Placebo ASA
12
9.3
10
8
Clopidogrel ASA
Death, MI, or Stroke
20 RRR P lt 0.001 N 12,562
6
4
2
0
3
6
9
0
12
Months of Follow-Up
N Engl J Med. 2001
24CURE - Bleeding Complications
Placebo ASA(N 6303)
Clopidogrel ASA(N 6259)
P-Value
- Major bleeding 2.7
3.7 0.001 - Life-threatening bleeding 1.8
2.2 NS - Non-life-threatening bleeding
0.9 1.5 0.002 - Minor bleeding 2.4
5.1 lt 0.001
N Engl J Med, 2001
25CURE PCI Sub-StudyUpstream Clopidogrel Before
PCI
15
12.6
Placebo ASA
8.8
10
Clopidogrel ASA
Death or Nonfatal MI
5
31 RRR P 0.002N 2658
0
0
100
200
300
400
Mehta S, Lancet 2001
Days of follow-up
Median Time to PCI 6 Days
26Hospital CareAnti-Ischemic Therapy (1)
- ?-blocker (IV?oral) if not contraindicated
- Non-dihydropyridine Ca2 antagonist if ?-blocker
contraindicated and no LV dysfunction, for
recurrent ischemia - ACE inhibitor if ? BP persists with NTG
?-blocker, for pts with CHF or diabetes
27Hospital CareAnti-Ischemic Therapy (2)
- ACE inhibitor for all ACS pts
- Extended-release Ca2 blocker instead of
?-blocker - Immediate-release Ca2 blocker with ?-blocker
- Long-acting Ca2 blocker for recurrent ischemia,
if no contraindications and NTG ?-blocker used
fully
28Hospital CarePlatelet GP IIb/IIIa Inhibitors (1)
- Any GP IIb/IIIa inhibitor ASA/Heparin for all
patients, if cath/PCI planned - Eptifibatide or tirofiban ASA/Heparin for
high-risk patients in whom early cath/PCI is not
planned - Any GP IIb/IIIa inhibitor for patients already on
ASA Heparin clopidogrel, if cath/PCI is
planned
High-risk Age gt 75 prolonged, ongoing CP
hemodynamic instability rest CP w/ ST ? VT
positive cardiac markers
29Platelet GP IIb/IIIa Inhibition for Non-ST ?
ACSPrimary Endpoint Results from the 5 Major RCTs
20
Placebo
17.9
GP IIb/IIIa
15.7
14.2
15
12.9
12.8
11.8
11.7
10.3
Primary Endpoint
10
5.6
5
3.8
P 0.04
P 0.01
P 0.004
P 0.48
P 0.33
0
PURSUIT30 days
PRISM48 hrs
PRISM PLUS7 days
PARAGON A30 days
PARAGON B30 days
30Platelet GP IIb/IIIa Inhibition for Non ST ?
ACSEnhanced Benefit in Patients Undergoing
Early PCI
Placebo
GP IIb/IIIa
18.5
20
16.7
11.6
11.6
10.2
30-Day Death or MI
10
5.9
0
PRISM-PLUS
PURSUIT
PARAGON-B
31GP IIb/IIIa Blockade Before and After PCI
CAPTURE, PURSUIT, PRISM-PLUS
Before PCI
Post-PCI
10
Placebo GP IIb/IIIa inhibitor
8.0
8
6
N12,296 P0.001
Death or MI
4.9
4.3
4
2.9
N2754 P0.001
2
0
24 h
48 h
72 h
24 h
48 h
0
PCI
Boersma, Circulation, 1999
32Platelet GP IIb/IIIa Blockade for Non-ST ? ACS
Pre-Treatment Before CABG in PURSUIT
40
32.7
30
27.6
p 0.02
20
Death or MI ()
10
Eptifibatide
Placebo
0
0
30
60
90
120
150
180
Days After Randomization
Marso, Circulation 2000
33Hospital CarePlatelet GP IIb/IIIa Inhibitors (2)
- Eptifibatide or tirofiban ASA/Heparin for
patients without continuing ischemia in whom PCI
is not planned - Abciximab for patients in whom PCI is not planned
34Prolonged Infusions of Abciximab for Non-ST ?
ACS
CAPTURE GUSTO-IV ACS
- Short duration of chest pain (? 10 mins)
- ST ? (? 0.5 mm) or elevated TnI / TnT
- No angiography expected for 48 hrs
- Medical management anticipated
- Medically refractory unstable angina
- Culprit lesion identified during angiography
- Mandatory treatment period (18-24h) pre- PCI
- Infusion stopped 1 hr after PCI completed
35CAPTURE Results
10
8
6
4
2
0
12
24
36
Hours
36GP IIb/IIIa Inhibition for Non-ST-Elevation ACS
30-Day Death or Nonfatal MI
n
Trial
Risk Ratio 95 CI
Placebo
GP IIb/IIIa
7.1
PRISM
5.8
3,232
PRISM PLUS
11.9
10.2
1,915
PARAGON A
11.7
11.3
2,282
PURSUIT
15.7
14.2
9,461
PARAGON B
11.4
10.5
5,165
GUSTO-IV ACS
8.0
8.7
7,800
0.92 (0.86, 0.995) p 0.037
11.5
10.7
Pooled
29,855
0.5
1.0
1.5
Placebo Better
GP IIb/IIIa Better
Boersma, Lancet 2002
37Hospital CareConservative vs. Invasive
Strategies (1)
- Early invasive strategy in high-risk patients
with any of the following - - Recurrent ischemia, despite meds
- - Elevated Troponin I or T
- - New ST-segment depression
- - New CHF symptoms
- - High-risk stress test findings
- - LV dysfunction (EF lt 40)
- - Hemodynamic instability, sustained VT
- - PCI within 6 months, prior CABG
38Hospital CareConservative vs. Invasive
Strategies (2)
- Either strategy in low- to moderate-risk patients
without contraindications to revascularization - Early invasive strategy for patients with
repeated ACS presentations, without high-risk
features or ongoing ischemia
39FRISC-II Mortality at One-Year Invasive Vs.
Conservative Management Strategies
.04
Non-Invasive (n 1235)
.03
Probability of Death
.02
Invasive (n 1222)
.01
Invasive Noninvasive RR (95 CI) 2.2
4.0 0.56 (0.35 - 0.89) p 0.018
0
360
180
90
30
0
Wallentin, Lancet 2000
40TACTICS-TIMI-18 Primary Endpoint Death, MI,
Rehospitalization for ACS at 6 Months
19.4 15.9
20
16
12
O.R 0.78 95 CI (0.62, 0.97) p0.025
Patients
8
4
CONS
INV
0
0
1
2
3
4
5
6
Time (months)
Cannon C, AHA 2000
41Early Invasive Management and Enhanced
Anti-Platelet Therapy
FRISC II
TACTICS-TIMI 18
Low Molecular Weight Heparin
GP IIb/IIIa Inhibitor
0.14
CONS
0.12
0.10
CONS
0.08
INV
Probability of MI
0.06
INV
0.04
0.02
0.00
0
30
60
90
120
150
180
Time (days)
FRISC-II Investigators, Lancet, 1999
Cannon, AHA 2000
42Discharge/Post-Discharge Medications
- ASA, if not contraindicated
- Clopidogrel, when ASA contraindicated
- Aspirin Clopidogrel, for up to 9 months
- ?-blocker, if not contraindicated
- Lipid ? agents diet, if LDL gt130 mg/dL
- ACE Inhibitor CHF, EF lt 40, DM, or HTN
43LIPID Trial - Statin Therapy for Patients with
Recent ACS
15
- P 0.00002
- 23 reduction
- 31 deaths avoided
- per 1000 patients
Placebo
10
Cumulative Mortality
5
Pravastatin
0
0
1
2
3
4
5
6
7
Years Since Randomization
LIPID Study Group, NEJM, 1998
44HOPE Primary Results Broad Benefits of ACE
Inhibitors
0.2
Ramipril
Placebo
0.15
Death, MI, or Stroke
0.1
plt0.001
0.05
0
0
500
1000
1500
Days of Follow-up
45Risk Factor Modification
- Smoking Cessation Counseling
- Dietary Counseling and Modification
- Cardiac Rehabilitation Referral
- HTN Control (BP lt 130/85 mm Hg)
- Tight Glycemic Control in Diabetics