case studies in the management of acs with gp iib/iiia inhibitors
TRANSCRIPT
Case Studies in the Management of ACS Case Studies in the Management of ACS With GP IIb/IIIa InhibitorsWith GP IIb/IIIa Inhibitors
Medical EditorsMedical Editors
H. Vernon Anderson, MDH. Vernon Anderson, MDCardiology DivisionCardiology Division
University of Texas Health Sciences CenterUniversity of Texas Health Sciences CenterHouston, TXHouston, TX
James J. Ferguson III, MDJames J. Ferguson III, MDCardiology ResearchCardiology ResearchTexas Heart InstituteTexas Heart Institute
Houston, TXHouston, TX
Jonathan D. Marmur, MDJonathan D. Marmur, MDInterventional CardiologyInterventional Cardiology
Mount Sinai Medical CenterMount Sinai Medical CenterNew York, NY New York, NY
E. Magnus Ohman, MDE. Magnus Ohman, MDDuke University Medical CenterDuke University Medical Center
Durham, NCDurham, NC©©2000 Academy for Healthcare Education. No material may be reproduced in whole or in part without 2000 Academy for Healthcare Education. No material may be reproduced in whole or in part without
written permission from the Academy for Healthcare Educationwritten permission from the Academy for Healthcare Education
Case 1: PresentationCase 1: Presentation
• 64-year-old woman with 64-year-old woman with typical chest pain, typical chest pain, shortness of breath, shortness of breath, diaphoresis at rest diaphoresis at rest
• Current Current medications: HRTmedications: HRT
• Hemodynamically stableHemodynamically stable
• Physical exam Physical exam unremarkableunremarkable
• Treated with rt-PA, Treated with rt-PA, heparin, and aspirin heparin, and aspirin
• Resolution of chest Resolution of chest discomfort over discomfort over next hournext hour
• ECG on arrival to ED
• Repeat ECG
Case 1: Recurrent Chest PainCase 1: Recurrent Chest Pain
• One hour later patient develops recurrent One hour later patient develops recurrent chest pain and ECG is repeated chest pain and ECG is repeated
• Patient is given tirofiban and ECG is Patient is given tirofiban and ECG is repeated ½ hour laterrepeated ½ hour later
• Patient taken to cath labPatient taken to cath lab
Case 1: Post-InterventionCase 1: Post-Intervention
• Stent placed in RCAStent placed in RCA
• Final ECG demonstrates no Final ECG demonstrates no progression to Q-wave MIprogression to Q-wave MI
Reocclusion After Thrombolysis Is a Reocclusion After Thrombolysis Is a Relatively Common PhenomenonRelatively Common Phenomenon
Case 1: Lessons LearnedCase 1: Lessons Learned
85%85%
75%75%
57%57%
44%44%
29%29%
25%25%
34%34%
13%13%
90-Minute Patency90-Minute Patency
60-Minute Patency60-Minute Patency
TIMI Grade 3 FlowTIMI Grade 3 Flow
No Myocardial PerfusionNo Myocardial Perfusion
Intermittent PatencyIntermittent Patency
Optimal ReperfusionOptimal Reperfusion
Moliterno DJ, Topol EJ. Moliterno DJ, Topol EJ. Thromb HaemostasisThromb Haemostasis. 1997;78:214-219.. 1997;78:214-219.
ReocclusionReocclusion
25%25%
6277
27
1916
17
72
43
0
20
40
60
80
100 TIMI 2
TIMI 3
100 mg-
117
Cannon. Cannon. J Am Coll CardiolJ Am Coll Cardiol. 1999;34:1395-1402. . 1999;34:1395-1402.
t-PAt-PAAbciximabAbciximab
N=N=
50 mg+53
100 mg-
215
50 mg+97
Use of GP IIb/IIIa Inhibitors With Reduced Use of GP IIb/IIIa Inhibitors With Reduced Dose Thrombolytic Improves ReperfusionDose Thrombolytic Improves Reperfusion
Case 1: Lessons LearnedCase 1: Lessons Learned
60 Minutes60 Minutes 90 Minutes90 Minutes
70%
91%
78%
94%
*P*P=0.009=0.009†† PP=0.01=0.01**
††
% o
f P
atie
nts
% o
f P
atie
nts
0
2
4
6
8
10Instrument
Spontaneous
Intracranial
0
2
4
6
8
10Major HemorrhageMajor Hemorrhage
100-
STD
Antman et al. Antman et al. CirculationCirculation. 1999;99:2720-2732.. 1999;99:2720-2732.
t-PA (mg)t-PA (mg)AbciximabAbciximabHeparinHeparin
MortalityMortality
N=235N=103
N=70
50+
Low
50+
Very Low
% o
f P
atie
nts
% o
f P
atie
nts
100-
STD
50+
Low
50+
Very Low
N=235
N=103
N=70
Use of GP IIb/IIIa Inhibitors With Reduced Use of GP IIb/IIIa Inhibitors With Reduced Dose Thrombolytic Benefits SafetyDose Thrombolytic Benefits Safety
Case 1: Lessons LearnedCase 1: Lessons Learned
Case 2: PresentationCase 2: Presentation
• 76-year-old man presents with crescendo 76-year-old man presents with crescendo angina over past 2 weeksangina over past 2 weeks
• Hx of inferior non–Q-wave MI 6 months ago, Hx of inferior non–Q-wave MI 6 months ago, medically managedmedically managed
• Treated with aspirin and heparin in the EDTreated with aspirin and heparin in the ED
• Chest discomfort persists and patient taken Chest discomfort persists and patient taken to cath labto cath lab
Case 2: Post-StentCase 2: Post-Stent Post-GP IIb/IIIaPost-GP IIb/IIIa
• Patient given abciximabPatient given abciximab
• Reinjection of RCA after Reinjection of RCA after 5 minutes of therapy5 minutes of therapy
• Stent placed in area of lesionStent placed in area of lesion
• No reflow seen distal to stent No reflow seen distal to stent
Zhao et al. Zhao et al. CirculationCirculation. 1999;100:1609-1615.. 1999;100:1609-1615.
Thrombus Is Less Common and Flow Is Thrombus Is Less Common and Flow Is Better With Early GP IIb/IIIa UseBetter With Early GP IIb/IIIa Use
Case 2: Lessons LearnedCase 2: Lessons Learned
0
20
40
60
80
100
HeparinAlone
Tirofiban +Heparin
Fresh occlusion
Medium or large thrombus
Possible or small thrombus%
Pat
ient
s%
Pat
ient
s
Grade 2Grade 1Grade 0
TIMI Flow
HeparinAlone
Tirofiban +Heparin
0
20
40
60
80
100
Zhao et al. Zhao et al. CirculationCirculation. 1999;100:1609-1615.. 1999;100:1609-1615.
Long-Term Benefit of Reduced Long-Term Benefit of Reduced Thrombus and TIMI 3 FlowThrombus and TIMI 3 Flow
Case 2: Lessons LearnedCase 2: Lessons Learned
Odds ratioOdds ratioPP value value
Pat
ient
s W
ith E
vent
(%
)P
atie
nts
With
Eve
nt (
%)
20%
12%9%
Composite Refract IschMI/Death
10%7.4%
5.5%
1.68 1.68 0.020.02
1.44 1.44 0.080.08
1.72 1.72 <0.001<0.001
5
0
15
10
20
25
30TIMI 0-2 (n=298)TIMI 3 (n=1095)
5
0
15
10
20
25
30Thrombus (n=643)No thrombus (n=784)
Composite Refract IschMI/Death
1.68 1.68 0.0020.002
1.72 1.72 <0.001<0.001
Events at 30 DaysEvents at 30 Days
20%
10%12%
6%
9%
5%
1.44 1.44 <0.001<0.001
0
5
10
15
20
Basal Peak
Neumann et al. Neumann et al. CirculationCirculation. 1998;98:2695-2701.. 1998;98:2695-2701.
Better Coronary Flow Reserve Better Coronary Flow Reserve With GP IIb/IIIa UseWith GP IIb/IIIa Use
Case 2: Lessons LearnedCase 2: Lessons Learned
0.0
0.1
0.2
0.3
0.4
0.5
0
5
10
15
20
Difference From Baseline to 14 DaysDifference From Baseline to 14 Days
PP=0.007=0.007
C
oron
ary
Flo
w V
eloc
ity (
cm/s
)C
oron
ary
Flo
w V
eloc
ity (
cm/s
)
PP=0.15=0.15
PP=0.024=0.024
Cardiac Events Cardiac Events at 30 Daysat 30 Days
OR =0.2OR =0.2PP=0.031=0.031
W
all M
otio
n In
dex
Wal
l Mot
ion
Inde
x
% P
atie
nts
With
Eve
nts
% P
atie
nts
With
Eve
nts
HeparinAbciximab
Case 3: PresentationCase 3: Presentation
• 58-year-old man with 58-year-old man with diabetes presents to the diabetes presents to the ED with crescendo angina ED with crescendo angina culminating in rest painculminating in rest pain
• History of elevated History of elevated cholesterol, smoking, cholesterol, smoking, hypertension, and LVHhypertension, and LVH
• Current meds: aspirin, Current meds: aspirin, ACE inhibitor, insulinACE inhibitor, insulin
• Given heparin, IV NTG, Given heparin, IV NTG, Ca channel blocker, Ca channel blocker, admitted to CCUadmitted to CCU
• Developed recurrent Developed recurrent chest painchest pain
• Eptifibatide addedEptifibatide added
• TnI elevated to 1.4TnI elevated to 1.4
Case 3: Pre- and Post-StentCase 3: Pre- and Post-Stent
• Left coronary angiogram Left coronary angiogram preintervention with severe preintervention with severe proximal OM1 stenosisproximal OM1 stenosis
• Stent placed in OM1Stent placed in OM1
• Patient did well post-stent with no Patient did well post-stent with no recurrence of chest painrecurrence of chest pain
Théroux et al. Théroux et al. Circulation. Circulation. 1998;98:I-359.1998;98:I-359.
Risk Stratification: DiabetesRisk Stratification: DiabetesCase 3: Lessons LearnedCase 3: Lessons Learned
% P
atie
nts
% P
atie
nts
9.3%
1.2%
PP=0.004=0.00415.5%
4.7%
PP=0.002=0.002 19.2%
11.2%
PP=0.044=0.044
Day 7 Day 30 Day 180
5
0
15
10
20
Heparin(n=193)Tirofiban + heparin (n=169)
Cannon et al. Cannon et al. Circulation.Circulation. 1995;92:I-19. Abstract. 1995;92:I-19. Abstract.
Death/MI at 42 DaysDeath/MI at 42 Days Death/MI at 1 YearDeath/MI at 1 Year
Risk Stratification: Rest PainRisk Stratification: Rest PainCase 3: Lessons LearnedCase 3: Lessons Learned
0
5
10
15
20
25
30
0
5
10
15
20
25
30
4.24.2
18.418.4
1.41.40.00.0
10.910.9
26.326.3
7.37.3
0.00.0
Rest Pain <48 h
n=1091
Rest Pain <48 h
No Rest Pain
n=261
No Rest Pain
Dea
th/M
I, %
of
Pat
ient
sD
eath
/MI,
% o
f P
atie
nts
Dea
th/M
I, %
of
Pat
ient
s D
eath
/MI,
% o
f P
atie
nts
Unstable angina patientsPost-MI patients
Risk Stratification: TroponinRisk Stratification: TroponinCase 3: Lessons LearnedCase 3: Lessons Learned
Braunwald Class III Patients With Pos ECGBraunwald Class III Patients With Pos ECGAMI Ruled Out by CK-MB at 16 Hours AMI Ruled Out by CK-MB at 16 Hours
5.8%5.8%
23%23%
0
5
10
15
20
25
PP=0.02 =0.02
Com
posi
te E
ndpo
int
Com
posi
te E
ndpo
int
(30
days
—
MI,
Dea
th)
(30
days
—
MI,
Dea
th)
TnI-n = 69
TnI+n = 22
Galvani. Galvani. CirculationCirculation. 1997;95:2053-2059.. 1997;95:2053-2059.
15
10
5
0
0 5 10 15 20 25 30Follow-up (days)Follow-up (days)
Eve
nt R
ate
(%)
Eve
nt R
ate
(%)
TnI positive with heparinTnI positive with tirofiban
Case 3: Lessons LearnedCase 3: Lessons Learned
Heeschen et al. Heeschen et al. LancetLancet. 1999;354:1757-1762.. 1999;354:1757-1762.
Patients With Elevated Troponin-I Patients With Elevated Troponin-I Benefit From GP IIb/IIIa AdditionBenefit From GP IIb/IIIa Addition
Risk Stratification: Aspirin FailureRisk Stratification: Aspirin Failure
Alexander et al. Alexander et al. Am J Cardiol. Am J Cardiol. 1999;83:1147-1151.1999;83:1147-1151.
Case 3: Lessons LearnedCase 3: Lessons Learned
0
5
10
15
20
25
4-Day Death 30-Day Death/MI 6-MonthDeath/MI
CardiogenicShock
Heart Failure
No prior aspirin, n=3422
Prior aspirin, n=6039
% P
atie
nts
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Risk Stratification: Refractory AnginaRisk Stratification: Refractory AnginaMyocardial Infarction or DeathMyocardial Infarction or Death
ST depressionST depression
>3 Pain episodes >3 Pain episodes in previous 48 hin previous 48 h
Refractory anginaRefractory angina(proced and non-proced)(proced and non-proced)
Refractory anginaRefractory angina(non-proced)(non-proced)
%% PP value value
13.313.3
10.610.6
22.2722.27
10.310.3
0.0040.004
0.010.01
0.00010.0001
0.00010.0001
Case 3: Lessons LearnedCase 3: Lessons Learned
Bazzino. Bazzino. Am Heart JAm Heart J. 1999;137:322-331.. 1999;137:322-331.
Odds RatioOdds Ratio
Ischemic Chest Pain Ischemic Chest Pain Non–ST-Elevation ACS High-Risk IndicatorsNon–ST-Elevation ACS High-Risk Indicators
• Heparin and AspirinHeparin and Aspirin• Glycoprotein IIb/IIIa InhibitorGlycoprotein IIb/IIIa Inhibitor • NitratesNitrates• -Blocker-Blocker
• LV Dysfunction - HFLV Dysfunction - HF
• Diabetic - ElderlyDiabetic - Elderly
• Prior MIPrior MI
• Refractory SymptomsRefractory Symptoms
Consider TreatmentConsider Treatment
Positive MarkersPositive Markers
ST Depression ST Depression 1 mm 1 mm
Dynamic ECG Dynamic ECG
or
or
Definitely TreatDefinitely Treat
Case 3: Lessons LearnedCase 3: Lessons Learned
Indications for Initiation of GP IIb/IIIa TherapyIndications for Initiation of GP IIb/IIIa Therapy
Case 4: PresentationCase 4: Presentation
• 63 y/o male admitted to a 63 y/o male admitted to a community hospital with chest community hospital with chest discomfort and epigastric pain discomfort and epigastric pain persisting for 8 hourspersisting for 8 hours
• Hx smoking, Hx smoking, chol, GERD chol, GERD
• ECG: ST depressions V5-V6, T ECG: ST depressions V5-V6, T wave changes V2-V4wave changes V2-V4
• Started on Started on -blocker, nitrates, ASA -blocker, nitrates, ASA and heparinand heparin
• No relief of SxNo relief of Sx
• CK 891; CK-MB 102; TnI 5.8CK 891; CK-MB 102; TnI 5.8
• Tirofiban addedTirofiban added
• Pt became pain free 3 hours laterPt became pain free 3 hours later
• Transferred to tertiary centerTransferred to tertiary center
Case 4: AngiographyCase 4: Angiography
• Pt maintained on Pt maintained on tirofiban x 3 d w no Sxtirofiban x 3 d w no Sx
• Cath: Nl EF, Cath: Nl EF, posterolateral hypoposterolateral hypo
• Significant LAD, Cx, Significant LAD, Cx, RCA lesionsRCA lesions
• Decision to perform Decision to perform CABGCABG
• Sheath removed on Sheath removed on tirofibantirofiban
• Tirofiban cont’d until Tirofiban cont’d until 8 hours prior to surgery8 hours prior to surgery
• LIMA to LAD; SVG to LIMA to LAD; SVG to OM2, RCAOM2, RCA
• D/C’d day 5 post-opD/C’d day 5 post-op
Barr et al. Barr et al. Circulation.Circulation. 1998;98:I-504. Abstract. 1998;98:I-504. Abstract.
Use of GP IIb/IIIa in InterventionsUse of GP IIb/IIIa in InterventionsCase 4: Lessons LearnedCase 4: Lessons Learned
40
30
10
0
20
Medical RxMedical Rx PCIPCI CABGCABG
16.814.8
24.7
18.1
32.9
26.7OR=0.84OR=0.84
95% CI=0.56-1.2795% CI=0.56-1.27
OR=0.65OR=0.6595% CI=0.42-1.0195% CI=0.42-1.01
OR=0.80OR=0.8095% CI=0.40-1.095% CI=0.40-1.0
% D
eath
/MI/
RI/
UA
P R
eadm
it%
Dea
th/M
I/R
I/U
AP
Rea
dmit
(30
Day
s)(3
0 D
ays)
Heparin
Tirofiban + heparin
The PURSUIT Trial Investigators. The PURSUIT Trial Investigators. N Engl J Med.N Engl J Med. 1998;339:436-443. 1998;339:436-443.
16.715.6
11.6
14.5
0
5
10
15
20
25RR=31% RR=31%
PP=0.23=0.23
RR=7% RR=7% PP=0.01=0.01
% D
eath
or
MI
(30
Day
s)%
Dea
th o
r M
I (3
0 D
ays)
Early PCI(Within 72 h After Randomization)
Med Rx, Late PCI, CABG
Use of GP IIb/IIIa in InterventionsUse of GP IIb/IIIa in InterventionsCase 4: Lessons LearnedCase 4: Lessons Learned
Heparin
Eptifibatide + heparin
2 4 14 21 287
0.12
0.08
0.04
0.00
Heparin OnlyHeparin Only
RR=44%RR=44%
DaysDays
Tirofiban + HeparinTirofiban + Heparin
The PRISM-PLUS Study Investigators. The PRISM-PLUS Study Investigators. N Engl J MedN Engl J Med. 1998;338:1488-1497.. 1998;338:1488-1497.
Use of GP IIb/IIIa in InterventionsUse of GP IIb/IIIa in InterventionsCase 4: Lessons LearnedCase 4: Lessons Learned
PTCAPTCA
475 Patients Undergoing PTCA475 Patients Undergoing PTCAAll 1570 Patients EvaluatedAll 1570 Patients Evaluated
Drug Drug InfusionInfusion
Pro
babi
lity
of D
eath
or
MI
Pro
babi
lity
of D
eath
or
MI
24
Heparin OnlyHeparin Only
Tirofiban + Tirofiban + HeparinHeparin
RR=66%RR=66%
HoursHours
6 300 12 18 36 42 48
0.12
0.08
0.04
0.00
Scarborough et al. Scarborough et al. CirculationCirculation. 1999;100:437-444.. 1999;100:437-444.
Advantages of Short-Acting AgentsAdvantages of Short-Acting Agents
Case 4: Lessons LearnedCase 4: Lessons Learned
Inhi
bitio
n of
Agg
rega
tion
(%)
Inhi
bitio
n of
Agg
rega
tion
(%) 100
50
25
024
Time (h)Time (h)
0Infusion Time
24Postinfusion
48
75
Abciximab
Eptifibatide
Tirofiban
Death, MI at 1 YearDeath, MI at 1 Year
Steinhubl et al. Steinhubl et al. CirculationCirculation. 1998;98(suppl):I-573.. 1998;98(suppl):I-573.
Additional Benefit of GP IIb/IIIa in Patients Additional Benefit of GP IIb/IIIa in Patients Already on Aspirin and Ticlopidine Already on Aspirin and Ticlopidine
Case 4: Lessons LearnedCase 4: Lessons Learned
0
5
10
15
20
0
5
10
15
20P=0.021 P<0.001
11.2
6.9
15.8
6.7
PretreatmentPretreatment No PretreatmentNo Pretreatment
% o
f P
atie
nts
Dea
th/M
I%
of
Pat
ient
s D
eath
/MI
Stent +PlaceboN=466N=466
Stent +Abciximab
N=466N=466
Stent +Abciximab
N=328N=328
Stent +PlaceboN=343N=343
Case 5: Presentation and Pre-StentCase 5: Presentation and Pre-Stent
• 68-year-old man s/p stent to 68-year-old man s/p stent to RCA 3 years agoRCA 3 years ago
• Prolonged chest pain at homeProlonged chest pain at home
• Current meds: aspirinCurrent meds: aspirin
• In ED recurrent chest pain In ED recurrent chest pain relieved with NTGrelieved with NTG
• Troponin is elevatedTroponin is elevated
• In ED patient is given eptifibatide In ED patient is given eptifibatide for 48 hoursfor 48 hours
• Patient is stable over weekend Patient is stable over weekend
• Patient is brought to cath lab on Patient is brought to cath lab on MondayMonday
Case 5: Post-StentCase 5: Post-Stent
• LAD stent placedLAD stent placed
• Eptifibatide continued for Eptifibatide continued for 24 hours24 hours
• Patient discharged on Patient discharged on aspirin, clopidogrel, aspirin, clopidogrel, statinstatin
• Patient does well with no Patient does well with no recurrence of symptomsrecurrence of symptoms
0
2
4
6
8
10
Start GP IIb/IIIa Inhibitor/PlaceboStart GP IIb/IIIa Inhibitor/Placebo PCIPCI
N=2754N=2754PP=0.001=0.001
N=12,296N=12,296PP=0.001=0.001
+24 h +48 h +72 h +24 h +48 h
Boersma et al. Boersma et al. CirculationCirculation. 1999;100:2045-2048.. 1999;100:2045-2048.
4.3%4.3%
2.9%2.9%
8.0%8.0%
4.9%4.9%
Cum
ulat
ive
Inci
denc
eC
umul
ativ
e In
cide
nce
of D
eath
/Non
fata
l MI
(%)
of D
eath
/Non
fata
l MI
(%)
During Initial PharmacologicDuring Initial PharmacologicTreatmentTreatment
During 48 Hours After PCIDuring 48 Hours After PCI
ControlControl
GP IIb/IIIa inhibitorGP IIb/IIIa inhibitor
Benefits of Early Use of GP IIb/IIIa Benefits of Early Use of GP IIb/IIIa Include Cool Down and StabilizationInclude Cool Down and Stabilization
Case 5: Lessons LearnedCase 5: Lessons Learned
Case 5: Lessons LearnedCase 5: Lessons Learned
Pretreatment With GP IIb/IIIa Inhibitor Pretreatment With GP IIb/IIIa Inhibitor Reduces Adverse EventsReduces Adverse Events
DayDay
With
End
poin
t (%
)W
ith E
ndpo
int
(%)
HeparinHeparin
Tirofiban + HeparinTirofiban + Heparin
= -5.0%, RR=32%, = -5.0%, RR=32%, PP=0.004=0.004
0 30 60 90 120 150 1807
= -3.8%, RR=22%, = -3.8%, RR=22%, PP=0.029=0.029
= -4.4%, RR=19%, P=0.02
5
10
15
20
25
30
35
The PRISM-PLUS Investigators. The PRISM-PLUS Investigators. N Engl J MedN Engl J Med. 1998;338:1488-1497.. 1998;338:1488-1497.
Use of GP IIb/IIIa Inhibitors with LMWHUse of GP IIb/IIIa Inhibitors with LMWH
Cohen et al. Cohen et al. International J Cardiol.International J Cardiol. 1999;71:273-281. 1999;71:273-281.
Case 5: Lessons LearnedCase 5: Lessons Learned
Tirofiban/enoxaparin
Tirofiban/unfrac heparin
% I
nhib
ition
of
Pla
tele
t A
ggre
gatio
n%
Inh
ibiti
on o
f P
late
let
Agg
rega
tion 100
Hour 24 Hour 30 Hour 480
20
40
60
80
19.6
24.9
0
6
12
18
24
30
Tirofiban/enoxaparinTirofiban/unfrac heparin
Ble
edin
g tim
e (m
in)
Ble
edin
g tim
e (m
in)
Adjusted Mean
P=0.02
Major Bleeding (TIMI)Intracranial bleeding
Minor Bleeding (TIMI)
Transfusions (all blood products)
Platelets 90,000/mm3
1.4%0.0%
10.5%
4.0%
1.9%
0.8%0.0%
8.0%
2.8%
0.8%
Tirofiban + HeparinTirofiban + Heparinn=773n=773
HeparinHeparinn=797n=797
The PRISM-PLUS Investigators. The PRISM-PLUS Investigators. N Engl J MedN Engl J Med. 1998;338:1488-1497.. 1998;338:1488-1497.AGGRASTATAGGRASTAT®® package insert. package insert.
PP Value Value
NSNS
NS
NS
NS
Adverse Events: No Significant Rise in Adverse Events: No Significant Rise in Bleeding RatesBleeding Rates
Case 5: Lessons LearnedCase 5: Lessons Learned
Case 6: PresentationCase 6: Presentation
• 65-year-old man presents to ED with angina at rest65-year-old man presents to ED with angina at rest
• Patient has history of claudication, stroke 1 year ago with no residual deficit, Patient has history of claudication, stroke 1 year ago with no residual deficit, MI 5 y ago, CABG MI 5 y ago, CABG 3, diabetes, hypertension 3, diabetes, hypertension
• Meds: aspirin, beta blocker, NTG, statin, insulinMeds: aspirin, beta blocker, NTG, statin, insulin
• Patient presents to community hospitalPatient presents to community hospital
• ECG shows new ST ECG shows new ST laterally laterally
• Patient is given enoxaparin, IV NTGPatient is given enoxaparin, IV NTG
Case 6: Pre- and Post-StentCase 6: Pre- and Post-Stent
• Recurrent chest Recurrent chest painpain
• Tirofiban startedTirofiban started
• Patient Patient transferred to transferred to tertiary care tertiary care center; center; enoxaparin and enoxaparin and tirofiban continuedtirofiban continued
• Patient is taken to Patient is taken to cath lab next daycath lab next day
• Stent placed in Stent placed in SVG to LADSVG to LAD
0
5
10
15
20
Adverse Events in Patients Adverse Events in Patients Transferred to a Referral CenterTransferred to a Referral Center
% P
atie
nts
With
Eve
nts
% P
atie
nts
With
Eve
nts
* * PP<0.04 vs. heparin.<0.04 vs. heparin.PP values for transfer subgroup were not calculated, as this group was defined by postrandomization events. values for transfer subgroup were not calculated, as this group was defined by postrandomization events.Théroux et al. Théroux et al. Eur Heart J. Eur Heart J. 1998;19(suppl):50. Abstract.1998;19(suppl):50. Abstract.
Case 6: Lessons LearnedCase 6: Lessons Learned
3.9*
10.8
7.1*
13.8
10.3*
17.4
0
5
10
15
20
2.7
10.312.0
5.4
8.1
15.4
7 Days
30 Days
180 Days
Community HospitalCommunity Hospital
7 Days
30 Days
180 Days
TransferTransfer
Heparin alone Tirofiban + heparin
Tro
poni
n I
(ng/
mL)
Tro
poni
n I
(ng/
mL)
0
6
12
18 Heparin (n=52)
Tirofiban + heparin (n=53)
TnI Levels in UA/NQWMI Patients Treated TnI Levels in UA/NQWMI Patients Treated With Tirofiban: PRISM-PLUSWith Tirofiban: PRISM-PLUS
Baseline LevelsBaseline Levels Peak LevelsPeak Levels
Hahn et al. Hahn et al. J Am Coll Cardiol.J Am Coll Cardiol. 1998;31(suppl A):229A. 1998;31(suppl A):229A.
3.1
5.2
15.5
1.6
PP=NS=NS
PP=0.017=0.017
Case 6: Lessons LearnedCase 6: Lessons Learned
Antman et al. Antman et al. Circulation. Circulation. 1999;100:1602-1608.1999;100:1602-1608.
UFH UFH Enox Enox OR OR Day Day (%)(%) (%)(%) (95% CI) (95% CI) % % PP
8 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
2 1.8 1.4 0.80 (0.55-1.16) 20 0.24
1 20.5Odds RatioOdds Ratio
Favors Favors EnoxaparinEnoxaparin
Favors Favors UFHUFH
Unfractionated Heparin Versus Enoxaparin in UA Unfractionated Heparin Versus Enoxaparin in UA (ESSENCE/TIMI 11B Pooled Analysis)(ESSENCE/TIMI 11B Pooled Analysis)
Case 6: Lessons LearnedCase 6: Lessons Learned
Death/MIDeath/MI
GP IIb/IIIa Blockers and Platelet Count: GP IIb/IIIa Blockers and Platelet Count: Relation to Unfractionated Heparin UseRelation to Unfractionated Heparin Use
Case 6: Lessons LearnedCase 6: Lessons Learned
Kereiakes et al. Kereiakes et al. Am J CardiolAm J Cardiol. 1999;84 (suppl 6A):67P.. 1999;84 (suppl 6A):67P.
Platelet CountPlatelet Count
0
1
2
3
4
5
6
<100,000<100,000 <50,000<50,000 <20,000<20,000
NICE 4EPIC B+IEPILOG(SD)EPILOG (LD)EPISTENT (PTCA)EPISTENT (Stent)
% P
atie
nts
% P
atie
nts
Case 7: PresentationCase 7: Presentation
• 85-year-old man presents with recurrent 85-year-old man presents with recurrent pulmonary edema in acute respiratory pulmonary edema in acute respiratory distressdistress
• Hx DM, moderate AS, 3VD, EF 30%, Hx DM, moderate AS, 3VD, EF 30%, COPD, AAA repair 10 y agoCOPD, AAA repair 10 y ago
• Current meds: aspirin, beta blocker, Current meds: aspirin, beta blocker, furosemide, glyburide, bronchodilators, furosemide, glyburide, bronchodilators, nitratesnitrates
• Intubated in ED, taken to CCUIntubated in ED, taken to CCU
• Heparin added, further diuresisHeparin added, further diuresis
• Tirofiban addedTirofiban added
• CK peak 312 (<3CK peak 312 (<3ULN) ULN)
• MB peak 3.9 (<3MB peak 3.9 (<3ULN)ULN)
• TnI 2.3TnI 2.3
Case 7: Pre-InterventionCase 7: Pre-Intervention• Taken to cath lab: IABP, temp pacemaker, dopamine addedTaken to cath lab: IABP, temp pacemaker, dopamine added
• Severe 3VD with significant LM and LAD lesions; RCA occludedSevere 3VD with significant LM and LAD lesions; RCA occluded
• Declined by CV surgery as “too high risk”Declined by CV surgery as “too high risk”
RCARCA LCALCA
Case 7: Post-InterventionCase 7: Post-Intervention• Rotational atherectomy LM and LAD, 1.5 mm burrRotational atherectomy LM and LAD, 1.5 mm burr
• 3.0 3.0 15 mm balloon to 12 atm 3.0 15 mm balloon to 12 atm 3.0 16 mm GFX 16 mm GFX stents (3 deployed) stents (3 deployed)
• Tirofiban continued for 12 hours post-procedureTirofiban continued for 12 hours post-procedure
• Extubated on 3rd day; discharged home on 8th dayExtubated on 3rd day; discharged home on 8th day
RotablatorRotablator
Stent (1 of 3)Stent (1 of 3)
Mortality Benefits With Use of GP IIb/IIIa Mortality Benefits With Use of GP IIb/IIIa Inhibitors With StentsInhibitors With Stents
Topol et al. Topol et al. LancetLancet. 1999;354:2019-2024.. 1999;354:2019-2024.
Case 7: Lessons LearnedCase 7: Lessons Learned
Stent + placebo (n=809)Stent + placebo (n=809)Stent + abciximab (n=794)Stent + abciximab (n=794)Balloon angioplasty + abciximab (n=796)Balloon angioplasty + abciximab (n=796)
Time Since Randomization (days)Time Since Randomization (days)
0.0
1.5
2.0
2.5
3.0
1.0
0.5
0 60 120 240 360180 300
Pro
port
ion
of D
eath
s (%
)P
ropo
rtio
n of
Dea
ths
(%)
2.4%
P P <0.037<0.0372.1%
1.0%
Case 7: Lessons LearnedCase 7: Lessons Learned
Composite Composite Re-analysisRe-analysis
RR =16%RR =16%= -1.9%= -1.9%
P P = 0.16= 0.16
0 5 10 15 20 25 30Day
0
3
6
9
12 Placebo + HeparinPlacebo + Heparin
Tirofiban + HeparinTirofiban + Heparin
=-3.3%
P < 0.005RR = 38%
=-2.8%
P = 0.022RR = 27%
DayDay0 5 10 15 20 25 30
0
2
4
6
8
10
12
% W
ith C
ompo
site
End
poin
t%
With
Com
posi
te E
ndpo
int
Placebo + HeparinPlacebo + Heparin
Tirofiban + HeparinTirofiban + Heparin
P = 0.002
= -3.5%RR = 40%
= -2.5%= -2.5%RR = 24%RR = 24%P P = 0.052= 0.052
2.9%RR = 30%P = 0.016
(Death, MI, (Death, MI, allall revascularization) revascularization) (Death, MI, (Death, MI, urgenturgent revascularization) revascularization)
The RESTORE Investigators. The RESTORE Investigators. CirculationCirculation. 1997;96:1445-1453.. 1997;96:1445-1453.
Early Use of GP IIb/IIIa Results in Lower Early Use of GP IIb/IIIa Results in Lower Event Rate in High-Risk InterventionsEvent Rate in High-Risk Interventions
Case Studies: ConclusionsCase Studies: Conclusions
• If there are no contraindications, GP IIb/IIIa inhibitors should If there are no contraindications, GP IIb/IIIa inhibitors should be incorporated into early medical management of these be incorporated into early medical management of these patients with ACS:patients with ACS:
– All NQWMI patientsAll NQWMI patients
– UA patients if they have “high-risk” featuresUA patients if they have “high-risk” features
• If not already started, and there are no contraindications, If not already started, and there are no contraindications, GP IIb/IIIa inhibitors should be used in all patients with ACS GP IIb/IIIa inhibitors should be used in all patients with ACS undergoing percutaneous interventionsundergoing percutaneous interventions