Transcript Case Studies in the Management of ACS with

Case Studies in the Management of ACS
With GP IIb/IIIa Inhibitors
Medical Editors
H. Vernon Anderson, MD
Cardiology Division
University of Texas Health Sciences Center
Houston, TX
James J. Ferguson III, MD
Cardiology Research
Texas Heart Institute
Houston, TX
Jonathan D. Marmur, MD
Interventional Cardiology
Mount Sinai Medical Center
New York, NY
E. Magnus Ohman, MD
Duke University Medical Center
Durham, NC
©2000
Academy for Healthcare Education. No material may be reproduced in whole or in part without
written permission from the Academy for Healthcare Education
Case 1: Presentation
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64-year-old woman with
typical chest pain,
shortness of breath,
diaphoresis at rest
Current
medications: HRT
Hemodynamically stable
Physical exam
unremarkable
Treated with rt-PA,
heparin, and aspirin
Resolution of chest
discomfort over
next hour
•
ECG on arrival to ED
•
Repeat ECG
Case 1: Recurrent Chest Pain
•
•
One hour later patient develops recurrent
chest pain and ECG is repeated
Patient is given tirofiban and ECG is
repeated ½ hour later
•
Patient taken to cath lab
Case 1: Post-Intervention
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•
Stent placed in RCA
Final ECG demonstrates no
progression to Q-wave MI
Case 1: Lessons Learned
Reocclusion After Thrombolysis Is a
Relatively Common Phenomenon
90-Minute Patency
85%
60-Minute Patency
75%
TIMI Grade 3 Flow
57%
No Myocardial Perfusion
25%
34%
44%
Intermittent Patency
Reocclusion
13%
Optimal Reperfusion
Moliterno DJ, Topol EJ. Thromb Haemostasis. 1997;78:214-219.
29%
25%
Case 1: Lessons Learned
Use of GP IIb/IIIa Inhibitors With Reduced
Dose Thrombolytic Improves Reperfusion
% of Patients
60 Minutes
100
91%
80
19
60
70%
78%
94%
TIMI 2
17
TIMI 3
16
27
†
*
40
20
90 Minutes
72
*P=0.009
62
77
43
0
t-PA
Abciximab
N=
100 mg
117
50 mg
+
53
Cannon. J Am Coll Cardiol. 1999;34:1395-1402.
100 mg
215
50 mg
+
97
†
P=0.01
Case 1: Lessons Learned
Use of GP IIb/IIIa Inhibitors With Reduced
Dose Thrombolytic Benefits Safety
10
Major Hemorrhage
% of Patients
8
6
N=103
Instrument
Spontaneous
Intracranial
N=235
Mortality
10
8
6
4
4
2
N=70
N=103
N=235
2
N=70
0
0
t-PA (mg)
Abciximab
Heparin
100
STD
50
+
Low
50
+
Very Low
Antman et al. Circulation. 1999;99:2720-2732.
100
STD
50
+
Low
50
+
Very Low
Case 2: Presentation
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•
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•
76-year-old man presents with crescendo
angina over past 2 weeks
Hx of inferior non–Q-wave MI 6 months ago,
medically managed
Treated with aspirin and heparin in the ED
Chest discomfort persists and patient taken
to cath lab
Case 2: Post-Stent
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•
Stent placed in area of lesion
No reflow seen distal to stent
Post-GP IIb/IIIa
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•
Patient given abciximab
Reinjection of RCA after
5 minutes of therapy
Case 2: Lessons Learned
Thrombus Is Less Common and Flow Is
Better With Early GP IIb/IIIa Use
% Patients
100
100
80
Fresh occlusion
80
60
Medium or
large thrombus
60
40
Possible or
small thrombus
40
20
0
TIMI Flow
Grade 2
Grade 1
Grade 0
20
Heparin
Alone
Tirofiban +
Heparin
Zhao et al. Circulation. 1999;100:1609-1615.
0
Heparin
Alone
Tirofiban +
Heparin
Case 2: Lessons Learned
Long-Term Benefit of Reduced Thrombus
and TIMI 3 Flow
Events at 30 Days
Patients With Event (%)
30
30
Thrombus (n=643)
No thrombus (n=784)
25
20
20
10%
15
12%
9%
6%
5
12%
10
5%
0
10%
7.4%
9%
5.5%
5
0
Composite
Odds ratio
P value
25
20%
20%
15
10
TIMI 0-2 (n=298)
TIMI 3 (n=1095)
1.72
<0.001
MI/Death Refract Isch
1.44
<0.001
Zhao et al. Circulation. 1999;100:1609-1615.
1.68
0.002
Composite
1.72
<0.001
MI/Death Refract Isch
1.44
0.08
1.68
0.02
Case 2: Lessons Learned
Better Coronary Flow Reserve
With GP IIb/IIIa Use
Cardiac Events
at 30 Days
P=0.007
P=0.024
0.5
15
10
P=0.15
5
0.4
0.3
0.2
0.1
0.0
0
Basal
Peak
Neumann et al. Circulation. 1998;98:2695-2701.
20
% Patients With Events
20
Heparin
Abciximab
 Wall Motion Index
 Coronary Flow Velocity (cm/s)
Difference From Baseline to 14 Days
15
10
5
0
OR =0.2
P=0.031
Case 3: Presentation
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58-year-old man with
diabetes presents to the
ED with crescendo angina
culminating in rest pain
History of elevated
cholesterol, smoking,
hypertension, and LVH
Current meds: aspirin,
ACE inhibitor, insulin
Given heparin, IV NTG,
Ca channel blocker,
admitted to CCU
Developed recurrent
chest pain
Eptifibatide added
TnI elevated to 1.4
Case 3: Pre- and Post-Stent
•
Left coronary angiogram
preintervention with severe
proximal OM1 stenosis
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•
Stent placed in OM1
Patient did well post-stent with no
recurrence of chest pain
Case 3: Lessons Learned
Risk Stratification: Diabetes
20
Heparin
(n=193)
Tirofiban + heparin
(n=169)
P=0.044
P=0.002
19.2%
15.5%
% Patients
15
P=0.004
11.2%
10
9.3%
4.7%
5
1.2%
0
Day 7
Théroux et al. Circulation. 1998;98:I-359.
Day 30
Day 180
Case 3: Lessons Learned
Risk Stratification: Rest Pain
Death/MI at 42 Days
Death/MI at 1 Year
30
25
18.4
20
15
10
5
4.2
0
Rest Pain
<48 h
n=1091
1.4
0.0
No Rest
Pain
n=261
Cannon et al. Circulation. 1995;92:I-19. Abstract.
Death/MI, % of Patients
Death/MI, % of Patients
Unstable angina patients
Post-MI patients
30
26.3
25
20
15
10.9
10
7.3
5
0.0
0
Rest Pain
<48 h
No Rest
Pain
Case 3: Lessons Learned
Risk Stratification: Troponin
Braunwald Class III Patients With Pos ECG
AMI Ruled Out by CK-MB at 16 Hours
Composite Endpoint
(30 days — MI, Death)
25
20
23%
P=0.02
15
10
5.8%
5
0
TnIn = 69
Galvani. Circulation. 1997;95:2053-2059.
TnI+
n = 22
Case 3: Lessons Learned
Patients With Elevated Troponin-I
Benefit From GP IIb/IIIa Addition
TnI positive with heparin
TnI positive with tirofiban
Event Rate (%)
15
10
5
0
0
5
Heeschen et al. Lancet. 1999;354:1757-1762.
10
15
20
Follow-up (days)
25
30
Case 3: Lessons Learned
Risk Stratification: Aspirin Failure
25
No prior aspirin, n=3422
Prior aspirin, n=6039
% Patients
20
15
10
5
0
4-Day Death
30-Day Death/MI
Alexander et al. Am J Cardiol. 1999;83:1147-1151.
6-Month
Death/MI
Cardiogenic
Shock
Heart Failure
Case 3: Lessons Learned
Risk Stratification: Refractory Angina
Myocardial Infarction or Death
%
P value
ST depression
13.3
0.004
>3 Pain episodes
in previous 48 h
10.6
0.01
Refractory angina
22.27
(proced and non-proced)
0.0001
Refractory angina
(non-proced)
0.0001
10.3
0
1
2
3
4
5
6
7
8
Odds Ratio
Bazzino. Am Heart J. 1999;137:322-331.
9 10 11 12 13 14
Case 3: Lessons Learned
Indications for Initiation of GP IIb/IIIa Therapy
Ischemic Chest Pain
Non–ST-Elevation ACS High-Risk Indicators
Consider Treatment
Definitely Treat
ST Depression  1 mm
or
Positive Markers
or
Dynamic ECG 
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LV Dysfunction - HF
Diabetic - Elderly
Prior MI
Refractory Symptoms
Heparin and Aspirin
Glycoprotein IIb/IIIa Inhibitor
Nitrates
-Blocker
Case 4: Presentation
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63 y/o male admitted to a
community hospital with chest
discomfort and epigastric pain
persisting for 8 hours
Hx smoking,  chol, GERD
ECG: ST depressions V5-V6, T
wave changes V2-V4
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•
Started on -blocker, nitrates, ASA
and heparin
No relief of Sx
CK 891; CK-MB 102; TnI 5.8
Tirofiban added
Pt became pain free 3 hours later
Transferred to tertiary center
Case 4: Angiography
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Pt maintained on
tirofiban x 3 d w no Sx
Cath: Nl EF,
posterolateral hypo
Significant LAD, Cx,
RCA lesions
Decision to perform
CABG
Sheath removed on
tirofiban
Tirofiban cont’d until
8 hours prior to surgery
LIMA to LAD; SVG to
OM2, RCA
D/C’d day 5 post-op
Case 4: Lessons Learned
Use of GP IIb/IIIa in Interventions
Heparin
Tirofiban + heparin
% Death/MI/RI/UAP Readmit
(30 Days)
40
30
20
OR=0.80
95% CI=0.40-1.0
OR=0.65
95% CI=0.42-1.01
OR=0.84
95% CI=0.56-1.27
16.8
32.9
26.7
24.7
18.1
14.8
10
0
Medical Rx
Barr et al. Circulation. 1998;98:I-504. Abstract.
PCI
CABG
Case 4: Lessons Learned
Use of GP IIb/IIIa in Interventions
% Death or MI (30 Days)
25
20
Heparin
Eptifibatide + heparin
RR=31%
P=0.01
RR=7%
P=0.23
16.7
15.6
15
14.5
11.6
10
5
0
Early PCI
(Within 72 h After Randomization)
Med Rx, Late PCI, CABG
The PURSUIT Trial Investigators. N Engl J Med. 1998;339:436-443.
Case 4: Lessons Learned
Use of GP IIb/IIIa in Interventions
Probability of Death or MI
All 1570 Patients Evaluated
0.12
0.08
475 Patients Undergoing PTCA
0.12
RR=44%
0.08
RR=66%
Tirofiban +
Heparin
0.04
Heparin Only
Tirofiban + Heparin
0.04
Heparin Only
0.00
0.00
0 6 12 18 24 30 36 42 48
2 4 7
Hours
Drug
Infusion
PTCA
The PRISM-PLUS Study Investigators. N Engl J Med. 1998;338:1488-1497.
14
Days
21
28
Case 4: Lessons Learned
Inhibition of Aggregation (%)
Advantages of Short-Acting Agents
100
75
50
Eptifibatide
25
Abciximab
Tirofiban
0
24
0
Infusion Time
24
Postinfusion
Time (h)
Scarborough et al. Circulation. 1999;100:437-444.
48
Case 4: Lessons Learned
Additional Benefit of GP IIb/IIIa in Patients
Already on Aspirin and Ticlopidine
% of Patients Death/MI
Death, MI at 1 Year
20
Pretreatment
20
P=0.021
No Pretreatment
15.8
15
P<0.001
15
11.2
10
10
6.9
6.7
5
5
0
0
Stent +
Placebo
N=466
Stent +
Abciximab
N=466
Steinhubl et al. Circulation. 1998;98(suppl):I-573.
Stent +
Placebo
N=343
Stent +
Abciximab
N=328
Case 5: Presentation and Pre-Stent
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68-year-old man s/p stent to RCA
3 years ago
Prolonged chest pain at home
Current meds: aspirin
In ED recurrent chest pain
relieved with NTG
Troponin is elevated
In ED patient is given eptifibatide
for 48 hours
Patient is stable over weekend
Patient is brought to cath lab on
Monday
Case 5: Post-Stent
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LAD stent placed
Eptifibatide continued for
24 hours
Patient discharged on
aspirin, clopidogrel,
statin
Patient does well with no
recurrence of symptoms
Case 5: Lessons Learned
Benefits of Early Use of GP IIb/IIIa
Include Cool Down and Stabilization
Cumulative Incidence
of Death/Nonfatal MI (%)
During Initial Pharmacologic
Treatment
10
8
N=12,296
P=0.001
During 48 Hours After PCI
Control
GP IIb/IIIa inhibitor
N=2754
P=0.001
8.0%
6
4.9%
4.3%
4
2.9%
2
0
+24 h
+48 h
+72 h
+24 h
Start GP IIb/IIIa Inhibitor/Placebo
PCI
Boersma et al. Circulation. 1999;100:2045-2048.
+48 h
Case 5: Lessons Learned
Pretreatment With GP IIb/IIIa Inhibitor
Reduces Adverse Events
 = -4.4%, RR=19%, P=0.02
35
Heparin
With Endpoint (%)
30
25
Tirofiban + Heparin
20
15
 = -3.8%, RR=22%, P=0.029
10
5
 = -5.0%, RR=32%, P=0.004
0 7
30
60
90
Day
120
The PRISM-PLUS Investigators. N Engl J Med. 1998;338:1488-1497.
150
180
Case 5: Lessons Learned
100
30
80
Bleeding time (min)
% Inhibition of Platelet Aggregation
Use of GP IIb/IIIa Inhibitors with LMWH
60
40
20
Tirofiban/enoxaparin
Tirofiban/enoxaparin
Tirofiban/unfrac heparin
P=0.02
24
24.9
18
19.6
12
6
Tirofiban/unfrac heparin
0
0
Hour 24
Hour 30
Cohen et al. International J Cardiol. 1999;71:273-281.
Hour 48
Adjusted Mean
Case 5: Lessons Learned
Adverse Events: No Significant Rise in
Bleeding Rates
Tirofiban + Heparin
n=773
Heparin
n=797
P Value
1.4%
0.0%
0.8%
0.0%
NS
NS
10.5%
8.0%
NS
Transfusions
(all blood products)
4.0%
2.8%
NS
Platelets 90,000/mm3
1.9%
0.8%
NS
Major Bleeding (TIMI)
Intracranial bleeding
Minor Bleeding (TIMI)
The PRISM-PLUS Investigators. N Engl J Med. 1998;338:1488-1497.
AGGRASTAT® package insert.
Case 6: Presentation
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65-year-old man presents to ED with angina at rest
Patient has history of claudication, stroke 1 year ago with no residual deficit,
MI 5 y ago, CABG  3, diabetes, hypertension
Meds: aspirin, beta blocker, NTG, statin, insulin
Patient presents to community hospital
ECG shows new ST  laterally
Patient is given enoxaparin, IV NTG
Case 6: Pre- and Post-Stent
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•
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•
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Recurrent chest
pain
Tirofiban started
Patient transferred
to tertiary care
center;
enoxaparin and
tirofiban continued
Patient is taken to
cath lab next day
Stent placed in
SVG to LAD
Case 6: Lessons Learned
Adverse Events in Patients
Transferred to a Referral Center
Heparin alone
% Patients With Events
20
20
17.4
15.4
13.8
15
Tirofiban + heparin
15
10.8
12.0
10.3*
10
7.1*
10.3
10
8.1
5.4
5
3.9*
0
5
2.7
0
Community Hospital
Transfer
* P<0.04 vs. heparin.
P values for transfer subgroup were not calculated, as this group was defined by postrandomization events.
Théroux et al. Eur Heart J. 1998;19(suppl):50. Abstract.
Case 6: Lessons Learned
TnI Levels in UA/NQWMI Patients Treated
With Tirofiban: PRISM-PLUS
18
Heparin (n=52)
Troponin I (ng/mL)
Tirofiban + heparin (n=53)
P=0.017
15.5
12
P=NS
6
5.2
3.1
1.6
0
Baseline Levels
Hahn et al. J Am Coll Cardiol. 1998;31(suppl A):229A.
Peak Levels
Case 6: Lessons Learned
Unfractionated Heparin Versus Enoxaparin in UA
(ESSENCE/TIMI 11B Pooled Analysis)
Day
UFH
(%)
Enox
(%)
2
1.8
8
Death/MI
OR
(95% CI)
%
P
1.4
0.80 (0.55-1.16)
20
0.24
5.3
4.1
0.77 (0.62-0.95)
23
0.02
14
6.5
5.2
0.79 (0.65-0.96)
21
0.02
43
8.6
7.1
0.82 (0.69-0.97)
18
0.02
0.5
1
2
Odds Ratio
Favors
Favors
Enoxaparin
UFH
Antman et al. Circulation. 1999;100:1602-1608.
Case 6: Lessons Learned
GP IIb/IIIa Blockers and Platelet Count:
Relation to Unfractionated Heparin Use
6
NICE 4
EPIC B+I
EPILOG(SD)
EPILOG (LD)
EPISTENT (PTCA)
EPISTENT (Stent)
% Patients
5
4
3
2
1
0
<100,000
<50,000
Platelet Count
Kereiakes et al. Am J Cardiol. 1999;84 (suppl 6A):67P.
<20,000
Case 7: Presentation
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85-year-old man presents with
recurrent pulmonary edema in acute
respiratory distress
Hx DM, moderate AS, 3VD, EF 30%,
COPD, AAA repair 10 y ago
Current meds: aspirin, beta blocker,
furosemide, glyburide, bronchodilators,
nitrates
Intubated in ED, taken to CCU
Heparin added, further diuresis
Tirofiban added
CK peak 312 (<3ULN)
MB peak 3.9 (<3ULN)
TnI 2.3
Case 7: Pre-Intervention
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•
•
Taken to cath lab: IABP, temp pacemaker, dopamine added
Severe 3VD with significant LM and LAD lesions; RCA occluded
Declined by CV surgery as “too high risk”
RCA
LCA
Case 7: Post-Intervention
•
•
Rotablator
Stent (1 of 3)
•
•
Rotational atherectomy LM and LAD, 1.5 mm burr
3.0  15 mm balloon to 12 atm 3.0  16 mm GFX
stents (3 deployed)
Tirofiban continued for 12 hours post-procedure
Extubated on 3rd day; discharged home on 8th day
Case 7: Lessons Learned
Proportion of Deaths (%)
Mortality Benefits With Use of GP IIb/IIIa
Inhibitors With Stents
Stent + placebo (n=809)
Stent + abciximab (n=794)
Balloon angioplasty + abciximab (n=796)
3.0
2.5
2.4%
2.0
2.1%
P <0.037
1.5
1.0
1.0%
0.5
0.0
0
60
120
180
240
Time Since Randomization (days)
Topol et al. Lancet. 1999;354:2019-2024.
300
360
Case 7: Lessons Learned
Early Use of GP IIb/IIIa Results in Lower
Event Rate in High-Risk Interventions
Re-analysis
(Death, MI, all revascularization)
(Death, MI, urgent revascularization)
 = -2.8%
RR = 27% Placebo + Heparin
P = 0.022
12
 = -1.9%
RR =16%
P = 0.16
9
Tirofiban + Heparin
6
 = -3.3%
RR = 38%
P < 0.005
3
0
0
5
10
15
Day
20
25
30
% With Composite Endpoint
Composite
 = -2.5%
RR = 24%
P = 0.052
12
10
 = -2.9%
RR = 30%
P = 0.016 Placebo + Heparin
8
6
Tirofiban + Heparin
4
 = -3.5%
RR = 40%
P = 0.002
2
0
The RESTORE Investigators. Circulation. 1997;96:1445-1453.
0
5
10
15
Day
20
25
30
Case Studies: Conclusions
•
If there are no contraindications, GP IIb/IIIa inhibitors should
be incorporated into early medical management of these
patients with ACS:
– All NQWMI patients
– UA patients if they have “high-risk” features
•
If not already started, and there are no contraindications,
GP IIb/IIIa inhibitors should be used in all patients with ACS
undergoing percutaneous interventions