Case Studies in the Management of ACS With GP IIb/IIIa Inhibitors.

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


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



• 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


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


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


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


• 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


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.


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


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


Indications for Initiation of GP IIb/IIIa TherapyIndications for Initiation of GP IIb/IIIa Therapy


• 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


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.


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


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


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



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


= -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.


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



• 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.


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


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)


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


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


• 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.


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%


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


=-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


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

Case Studies in the Management of ACS With GP IIb/IIIa Inhibitors.

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Transcript of Case Studies in the Management of ACS With GP IIb/IIIa Inhibitors.