Interventional Pharmacology: The Basics

1
Interventional PharmacologyThe Basics

• Michael J. Cowley, FACC,FSCAI

Nothing to Disclose
2
Interventional Pharmacology

• Heparin (UFH)
• GP IIb/IIIa Receptor Antagonists
• Low Molecular Weight Heparins
• Direct Thrombin Inhibitors
• Thienopyridines

3
Interventional Pharmacology

• GP IIb/IIIa Receptor Antagonists
• Low Molecular Weight Heparins
• Direct Thrombin Inhibitors
• Thienopyridines

4
Adjunctive Therapy for ACS / PCI
GP 2b3a Agents
Anti Thrombins
Abciximab Eptifibatide Tirofiban
Heparin LMWH Bivalirudin
Clopidogrel pre-treatment how early? how
much?
5
Adjunctive Therapy for PCI
GP 2b3a Agents
Anti Thrombins
Abciximab Eptifibatide Tirofiban
Heparin LMWH DTI
Clopidogrel pre-treatment
6
Interventional Pharmacology
Beneficial Agents
UFH Clinical Experience,
Non-inferiority GP2b3a Numerous studies
(vs UFH alone) LMWH
ESSENCE, TIMI 11, INTERACT
SYNERGY, STEEPLE Clopdiogrel CURE,
PCI-CURE, CREDO Bivalirudin BAT, REPLACE 2,
ACUITY
7
Interventional Pharmacology
Beneficial Agents
UFH Clinical Experience,
Non-inferiority GP2b3a Numerous studies
(vs UFH alone) LMWH
ESSENCE, TIMI 11, INTERACT
SYNERGY, STEEPLE Clopdiogrel CURE,
PCI-CURE, CREDO,
CLARITY,COMMIT Bivalirudin BAT, REPLACE 2,
ACUITY
8
Interventional Pharmacology
Beneficial Agents
UFH Clinical Experience,
Non-inferiority GP2b3a Numerous studies
(vs UFH alone) LMWH
INTERACT, SYNERGY, STEEPLE Clopdiogrel
CURE, PCI-CURE, CREDO Bivalirudin BAT,
REPLACE 2, ACUITY
9
Interventional Pharmacology
10
Interventional Pharmacology
11
Unfractionated Heparin
12
UFH with PCI
13
Unfractionated Heparin
Disadvantages
Advantages

• Indirect thrombin inhibitor (does not inhibit
  clot-bound thrombin)
• Nonspecific binding to
• Plasma proteins
• Endothelial cells
• (variable anticoagulation level)
• Inhibited by platelet factor 4
• reduced effect in ACS
• Causes platelet aggregation
• Risk of HIT

• Multiple sites of action in coagulation cascade
  (IIa,Xa)
• Long history of successful clinical use
• Readily monitored by aPTT and ACT
• Very inexpensive

Hirsh J, et al. Circulation. 20011032994-3018
14
ACC/AHA/SCAI PCI Guidelines
Unfractionated Heparin
Class I

• UFH should be given to pts under-going PCI (Level
  of Evidence C)

15
GP IIb / IIIa Receptor Antagonists
16
GP IIb/IIIa Receptor Inhibition

STEMI PCI ACS Lysis
PCI
EPIC CAPTURE SPEED
RAPPORT EPILOG PRISM TIMI
14 ADMIRAL
RESTORE PRISM PLUS GUSTO 5 ISAR
2 IMPACT PURSUIT ASSENT 3
CADILLAC IMPACT 2 GUSTO 4 Impact
AMI ACE
EPISTENT ESPRIT
TARGET



17
GPIIb/IIIa Antagonists in PCI
30 Day Death / MI
Trial
Placebo
IIb/IIIa
N
Risk Ratio 95 CI
EPIC
9.6
6.6
2,099
IMPACT-II
8.5
7.0
4,010
EPILOG
9.1
4.0
2,792
CAPTURE
9.0
4.8
1,265
6.3
RESTORE
5.1
2,141
10.2
EPISTENT
5.2
2,399
ESPRIT
10.2
6.3
2,064
0.62 (0.55, 0.71) p lt 0.000000001
8.8
5.6
Pooled
16,770
0
0.5
1
1.5
2
Placebo Better
IIb/IIIa Antag Better
18
Abciximab in PCI Complex Lesions
30 day Events (D, MI, uTVR) EPIC and EPILOG

p.047
p.001
p.001
p.001
p.078
p.001
p.001
p.001
p.001
365 452 761 961 380
799 2994 2312 1896
Ellis JACC 1998 321619
19
Abciximab for Complex Lesions EPISTENT
30 day D, MI, uTVR

p0.17
plt0.001
230 267 517 468
20
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21
Benefits of GP IIb/IIIa by Troponin Status in
Clinical Trials
TnT-Negative
TnT-Positive
PARAGON-B
PRISM
CAPTURE
Combined
0.125
1
2
0.5
0.125
1
2
0.5
GP IIb/IIIa Better
GP IIb/IIIa Worse
GP IIb/IIIa Better
GP IIb/IIIa Worse
Newby KL Circulation 20011032891-2896
22
ISAR-REACT 2 Cumulative Incidence of Death, MI,
or Urgent TVR in Subsets With and Without
Elevated Troponin Levels (gt0.03 µg/L)
Placebo Group (N1010) Abciximab Group (N1012)

Troponin gt0.03 µg/L Log-Rank p 0.02
Troponin lt0.03 µg/L Log-Rank p .98
0
5
10
15
20
25
30
Days After Randomization
Adapted from Kastrati A JAMA 2006 2951531-1538
23
GP IIb/IIIa in Acute MI
Abciximab PCI in Acute MI Trials 30 Day Endpoint
(D, Re-MI, Urg TVR)

plt0.05
p0.005
p0.038
p0.023
p0.01
Stent N 401
Stent N 301
PTCA or Stent N 2082
Stent N 400
PTCA N 483
24
Anti-Platelet Therapy
25
ASA in UA/NSTEMI
Death or MI
p .0005
p .012
p .008
plt.0001
20
15
12
15
17.1
12.9
10.1
11.9
15
8
10
10
5.0
Patients ()
6.2
10
6.5
4
5
5
3.3
5
0
0
0
0
Placebo118
ASA121
Placebo279
ASA276
Placebo397
ASA399
Placebo 158
ASA 178

Lewis HD Jr NEJM 1983309396-403
Theroux P NEJM 19883191105-1111
Cairns JA NEJM 19853131369-1375
The RISC Group Lancet 1990336827-830
26
CURE Primary End Point MI/Stroke/CV Death
In addition to other standard therapies
Yusuf S N Engl J Med 2001345494-502
27
CURE PCI Substudy
0.10
N 2,658
Placebo
0.08
0.06
Clopidogrel
Cumulative Hazard Rates
0.04
31 RRR
p 0.002
0.02
0.00
100
200
300
0
400
Days of Follow-Up
The CURE Investigators Lancet August 2001
28
CREDO 1 Year Primary Outcome
Death, MI or Stroke
15
Placebo N1063

11.5
10
8.5
Clopidogrel N1053
5
27 RRR p 0.02
0
0
3
6
9
12
Months
29
CREDO 1 Year Primary Outcome
Timing of Benefit
Death, MI, Stroke

12
RRR 19.7 pNS
8
6.9
5.5
4
0
Day 28
Day 29 to 1 year
Composite
30
Clopidogrel Loading Dose for PCI

• 300 mg
• 600 mg
• 900 mg
• A fistful
• The whole bottle

31
Circulation 2005 1122946-2950
32
Clopidogrel Loading Doses
ISAR-CHOICE
ADP 5
ADP 20
Beckerath Circ Nov 2005
33
ISAR-CHOICE
Platelet Aggregation 4h after Clopidogrel Loading
5 µmol/L ADP
20 µmol/L ADP
B
A
p 0.001
p 0.001
120 100 80 60 40 20 0
120 100 80 60 40 20 0
ADP (20 µmol/L)-Induced Aggregation ()
ADP (5 µmol/L)-Induced Aggregation ()
p .01
p .59
p 0.01
p .59
300 mg
600 mg
900 mg
300 mg
600 mg
900 mg
n 20
n 20
n 20
n 20
n 20
n 20
Circles represent single measurements bars
denote mean SD
von Beckerath N, et al Circulation
20051122946-2950
34
ARMYDA-2 Trial
Primary Endpoint death, MI, or TVR at 30 days
255 patients with stable CAD or NSTEMI prior to
PCI 13 GP IIb/IIIa inhibitors 20 DES
14
12
12
p0.041
Randomized 4-8 hrs Pre-PCI
10
8
6
Clopidogrel Loading Dose 600 mg Pre-PCI
Clopidogrel Loading Dose 300 mg Pre-PCI
4
4
2
0
High Dose
Standard Dose
Patti G et al. Circulation 20051112099-2106
35
CREDO Study Timing of Loading Dose and 28-Day
Endpoint
Timing N Pretreat No Pretreat 3lt6
h 893 7.9 7.0 624h 851 5.8 9.4
RRR 13.4 p0.60
RRR 38.6 p0.05
RRR 18.5 P.23
CREDO Overall
0.4
0.6
0.8
1.0
1.2
Hazard Ratio (95 CI)
Steinhubl SR, et al JAMA. 20022882411-2420
36
Meta-analysis of Clopidogrel Pretreatment
MI before PCI ()
Clopidogrel NoTrial Pretreatment Pretreatment
PCI-CURE 3.6 5.1 CREDO n/a n/a PCI-CLARITY 4.0 6.
1 Overall 3.7 5.5
Favors Pretreatment
Favors No Pretreatment
OR 0.67 p0.005
1.0
0.25
2.0
0.5
OR (95 CI)
CV Death or MI after PCI ()
Clopidogrel No Trial Pretreatment Pretreatment PC
I-CURE 2.9 4.4 CREDO 6.0 7.1 PCI-CLARITY 3.3 5.4 O
verall 3.9 5.5
OR 0.71 p0.004
0.25
2.0
1.0
0.5
OR (95 CI)
Adapted with permission from Sabatine MS, et al.
JAMA. 20052941224-1232
37
Clopidogrel with PCI
Summary

• Pre-treatment effective if started gt 6 hr before
  PCI
• No advantage to load dose gt600 mg
• Beneficial effects evident out to 1 yr
• Optimal duration with DES unknown

38
LMWH with PCI
39
Low-Molecular-Weight Heparin
Disadvantages
Advantages

• Increased anti-Xa to anti-IIa activity ?
  inhibits thrombin generation more effectively
• Induces ? TFPI release vs UFH
• Not neutralized by platelet factor 4
• Less binding to plasma proteins ? more
  consistent anticoagulation
• Lower rate of HIT vs UFH
• Easy SC administration
• Long history of clinical studies and experience,
  FDA-approved indications
• Monitoring typically unnecessary

• Indirect thrombin inhibitor
• Less reversible than UFH
• Long half-life
• Renal clearance
• Risk of HIT

Hirsh J, et a. Circulation 20011032994-3018
40
Limitations of UFH

• Unpredictable anticoagulant effect
• Non-specific protein binding and saturable
  clearance mechanism
• Inactivation by platelet factor 4
• Platelet activation and aggregation

Antman EM Circulation 1996 94 911 Théroux
P N Engl J Med 1992 327 141 Cohen M
Circulation 1994 8981
41
Advantages of LMWH vs UFH

• No platelet activation
• Inhibits von Willebrand factor release
• Augments TFPI release
• Inhibits thrombin generation
• No rebound hypercoagulability

42
UFH Therapy
Does not provide Predictable Anticoagulation
43
Advantages of LMWH vs UFH

• No platelet activation
• Inhibits von Willebrand factor release
• Augments TFPI release
• Inhibits thrombin generation
• No rebound hypercoagulability

44
Enoxaparin in the Cath Lab
In Cath Lab
Transition to Cath Lab
NICE 1 NICE 4 ELECT Choussat Carnendran STEEPLE
Collet PEPCI PK study NICE 3 SYNERGY
45
Enoxaparin in PCI
Last dose of SQ Enox pre-PCI
Enox IV at PCI
Trial
GP 2b/3a
(none)
Collet
(none)
Yes
NICE-3
0.3 mg/kg
PEPCI
0.3 mg/kg
NICE-3
Yes
1.0 mg/kg
(none)
NICE-1
(none)
0.75 mg/kg
Yes
NICE-4
(none)
0.5 mg/kg
Choussat
0.5 or 0.75
(none)
STEEPLE
PCI
-12 hr
12 hr
-8 hr
Adapted from Ferguson J Invasive Cardiol 200012
(Suppl E)E10-3
46
Enoxaparin in PCI
Last dose of SQ Enox pre-PCI
Enox IV at PCI
Trial
GP 2b/3a
(none)
Collet
Yes
(none)
NICE-3
PEPCI
0.3 mg/kg
NICE-3
0.3 mg/kg
Yes
1.0 mg/kg
(none)
NICE-1
(none)
0.75 mg/kg
Yes
NICE-4
(none)
0.5 mg/kg
Choussat
PCI
-12 hr
12 hr
-8 hr
Adapted from Ferguson J Invasive Cardiol 200012
(Suppl E)E10-3
47
Peterson JL JAMA 2004 29289-96
48
LMWH vs UFH in PCI Trials
Pooled Results (15 studies)
Borentain, Montalescot ESC 2003
49
Enoxaparin in PCI Trials
Pooled Results
Borentain, Montalescot ESC 2003
50
Low Dose IV Enoxaparin for PCI

• 242 pts with elective PCI
• Single IV bolus of 0.5 mg/kg
• 26 (n64) given eptifibatide
• Peak anti-Xa level gt0.5 IU/mL in 97.5
• Immed sheath removal (4h after eptifibatide)
• 30 day MACE 2.5 Minor bleed 1.6
• Major bleed 0.4 (82 yo F hematoma/PxA on
  eptifibatide)

Choussat, Montalescot JACC 2002 40 1943-50
51
Low Dose Enoxaparin with PCI
Enox
Enox Eptifib
Choussat, Montalescot JACC 2002 40 1943-50
52
STEEPLE Trial
3528 pts with non-emergent single or multi-vessel
PCI
ACT adjusted UFH Target ACT 200-300 With GP
IIb/IIIa Target ACT 300-350 if no GP IIb/IIIa
n1230

• IV enoxaparin
• 0.75 mg/kg
• n1228

IV enoxaparin 0.5 mg/kg n1070
Primary Endpoint Major / minor bleeding
(non-CABG) at 48 hrs post-PCI Secondary
Endpoints - Percent reaching target
anticoagulation levels at start and end of PCI
- Composite of major bleed (48 hrs), mortality,
MI, Urg TVR at 30 days
Montalescot NEJM 20063551006-1017
53
STEEPLE Trial Primary Endpoint
Non-CABG Major or Minor Bleeding at 48 hrs
p0.014 vs UFH
p0.052 vs UFH
Lower bleeding rate was observed overall and in
the GP IIb/IIIa subgroup
Montalescot NEJM 20063551006-1017
54
STEEPLE Trial
Analysis of Major Bleeding
p0.007 vs UFH
p0.005 vs UFH
57 lower with Enoxaparin
Montalescot NEJM 20063551006-1017
55
STEEPLE Trial Secondary Endpoint
Patients reaching target anticoagulation levels
at the start and end of procedure
plt0.001 vs Enox
Montalescot NEJM 20063551006-1017
56
STEEPLE Trial Secondary Endpoint
Composite Major Bleed (non-CABG) at 48 hrs and
30 day incidence of Death, MI, or urgent TVR
p ns
No difference in Death or MI among groups
Montalescot NEJM 20063551006-1017
57
STEEPLE Trial
Summary

• Reduced dose enoxaparin had less major or minor
  bleeding at 48 hrs than UFH
• Lower dose IV enoxaparin for PCI offers a safety
  advantage over ACT-guided UFH

58
Superior Yield of the New strategy of Enoxaparin,
Revascularization GlYcoprotein IIb/IIIa
Inhibitors

• 10,027 ACS patients with 2 out of 3
  high-risk criteria
• Age gt 60
• () biomarkers
• () ECG ?s
• Randomized to enoxaparin vs UFH
• Invasive management strategy
• GP IIb/IIIa antagonists encouraged
• Primary endpoint Death / MI at 30 days

The Synergy Investigators JAMA 2004 292 45-54
59
SYNERGY
Efficacy at 30 days

p0.396
p0.135
p0.705
The Synergy Investigators JAMA 2004 292 45-54
60
SYNERGY
In Hospital Procedures

• Enoxaparin UFH (n 4993) (n 4985)
• Cath during Hosp () 92.1 92.0
• Time to cath (hrs) 21.7 21.5 (6.3,
  43.6) (6.3, 42.6)
• Coronary Intervention () 46.5 47.4
• Time to PCI (hrs) 22.7 22.5 (6.4,
  48.8) (6.3, 48.1)
• CABG () 19.3 18.0

Median (25th, 75th)
pNS
The Synergy Investigators JAMA 2004 292 45-54
61
SYNERGYOutcomes with Consistent Therapy
p0.0039 RRR 16.4
p0.0029 RRR 17.9

pns
pns
n3398
n2740
n2627
n3010
Per Protocol
Intent-to-treat
Consistent therapy no pre-randomized therapy,
or randomized to the same therapy they had been
receiving
The Synergy Investigators JAMA 2004 292 45-54
62
ACC/AHA/SCAI PCI Guidelines
LMWH

• Class IIa
• LMWH is a reasonable alternative to UFH in pts
  with UA/NSTEMI undergoing PCI (Level of Evidence
  B)
• Class IIb
• LMWH may be considered as an alternative to UFH
  in pts with STEMI undergoing PCI (Level of
  Evidence B)

63
Bivalirudin
64
Bivalirudin
UFH
LMWH
Konkle BA, Schafer AI. In Zipes DP, Libby P,
Bonow RO, Braunwald E, eds.Braunwalds Heart
Disease. 7th ed, vol 2. Philadelphia Elsevier
Saunders 20052067-2092.
65
Direct Thrombin Inhibitors
Disadvantages
Advantages

• Predictable anticoagulant response
• Inhibits soluble and fibrin-bound thrombin
• Inhibits thrombin-induced platelet aggregation
• No HIT

• Needs continuous infusion
• No antidote
• Cost

Xiao Z, Theroux P Circulation 199897251-256
66
Direct Thrombin Inhibitors
Bivalirudin
BAT REPLACE 2 ACUITY
67
Direct Thrombin Inhibitors
Bivalirudin
REPLACE 2 ACUITY
68
REPLACE 2 Trial Design
69
REPLACE - 2
Primary Endpoint

p0.324
p0.43
plt0.001
p0.255
p0.435
70
REPLACE - 2
Outcomes

plt0.001
pns
pns
pns
pns
cytopenia
71
REPLACE - 2
Conclusions

• Non-inferior to heparin GP 2b3a receptor
  inhibitors
• Superior to heparin
• Reduced bleeding, transfusion, and
  thrombocytopenia
• Reduced time of treatment

72
ACC/AHA/SCAI PCI Guidelines
Bivalirudin

• Class I
• For pts with HIT, it is recommended that
  bivalirudin or argatroban be used (Level of
  Evidence B)
• Class IIa
• It is reasonable to use bivalirudin as an
  alternative to UFH GPI in low-risk pts having
  elective PCI (Level of Evidence B)

73
ACUITY Study DesignFirst Randomization
Moderate- to high-risk patients with UA or
NSTEMIundergoing an invasive strategy (N
13,819)
Moderate-to high- risk ACS
Aspirin in all Clopidogrel dosing and
timing per local practice
Stratified by pre-angiography thienopyridine
treatment
Stone GW, et al Am Heart J 2004 148764775
74
ACUITY Study Design Second Randomization
Moderate- to high-risk patients with unstable
anginaor NSTEMI undergoing an invasive strategy
(N 13,819)
UFH or Enoxaparin
Routine upstream GPI in all pts (2294)
GPI started in CCL for PCI only (2309)
UFH, Enoxaparin, or Bivalirudin
vs
Bivalirudin
Moderate- to high-risk ACS
Routine upstream GPI in all pts (2311)
R
GPI started in CCL for PCI only (2293)
Primary analysis
Aspirin in all Clopidogrel dosing and timing per
local practice
Bivalirudin alone N4612
Stone GW, et al Am Heart J 2004 148764775
75
ACUITY Primary End Point Measures
UFH/Enoxaparin GP IIb/IIIa vs Bivalirudin GP
IIb/IIIa
P value(noninferior)(superior)
UFH/Enox IIb/IIIa
Risk ratio 95 CI
Primary end point
Bival IIb/IIIa
RR (95 CI)
lt.001 .93
Net clinical outcome
11.7
11.8
1.01 (0.90-1.12)
.015 .39
Ischemic composite
Upper boundary non-inferiority
7.3
7.7
1.07 (0.92-1.23)
lt.001 .38
Major bleeding
5.7
5.3
0.93 (0.78-1.10)
ITT population
Bivalirudin GP IIb/IIIa better
UFH/Enox GP IIb/IIIa better
Stone GW, et al Presented at 55th ACC Annual
Meeting March 2006
76
ACUITY Primary End Point Measures
UFH/Enoxaparin GP IIb/IIIa vs Bivalirudin alone
P value(noninferior)(superior)
UFH/Enox IIb/IIIa
Risk ratio 95 CI
Primary end point
Bival alone
RR (95 CI)
lt.001 .015
Net clinical outcome
11.7
10.1
0.86 (0.77-0.97)
.02 .32
Ischemic composite
Upper boundary non-inferiority
7.3
7.8
1.08 (0.93-1.24)
lt.001 lt.001
Major bleeding
5.7
3.0
0.53 (0.43-0.65)
ITT population
Bivalirudin alone better
UFH/Enox IIb/IIIa better
Stone GW et al Presented at 55th ACC Annual
Meeting March 2006
77
Management Strategy (N13,819)
Medical Rx (n4,491)
CABG (n1,539)
32.2
11.4
56.4
PCI (n7,789)
78
ACUITY-PCI Net Clinical Outcomes

15
p0.001
10
Estimate
p (log rank)
Heparin IIb/IIIa (N2561)
13.5
5
Bivalirudin IIb/IIIa (N2609)
15.1
0.10
Bivalirudin alone (N2619)
0.049
11.7
0
0
5
10
15
20
25
30
35
Days from Randomization
Stone GW Presented at TCT October 2006
79
ACUITY- PCIComposite Ischemia
p (log rank)

Estimate
Heparin IIb/IIIa (N2561)
8.4
15
Bivalirudin IIb/IIIa (N2609)
0.15
9.4
Bivalirudin alone (N2619)
0.45
8.9
10
p0.36
5
0
0
5
10
15
20
25
30
35
Days from Randomization
Stone GW. Presented at TCT October 2006
80
Conclusions and Clinical Implications

• In patients with moderate and high risk ACS
  undergoing PCI
• Replacing upstream heparin with bivalirudin in
  pts treated with GP IIb/IIIa inhibitors provides
  similar clinical and angiographic outcomes
• Replacing heparin and GP IIb/IIIa inhibitors with
  bivalirudin alone results in similar rates of
  ischemia with markedly reduced hemorrhagic
  complications, thereby improving overall
  event-free survival

81
Conclusions and Clinical Implications

• In patients with moderate and high risk ACS
  undergoing PCI
• Replacing upstream heparin with bivalirudin in
  pts treated with GP IIb/IIIa inhibitors provides
  similar clinical and angiographic outcomes
• Replacing heparin and GP IIb/IIIa inhibitors with
  bivalirudin alone (with provisional IIb/IIIa
  inhibitor use in lt10 of pts) results in similar
  rates of ischemia with markedly reduced
  hemorrhagic complications, thereby improving
  overall event-free survival

82
ACUITY Timing Primary End Point
Routine Upstream GP IIb/IIIa vs Deferred PCI GP
IIb/IIIa
P value(non inferior)(superior)
Deferred IIb/IIIa
Risk ratio 95 CI
Primary end point
Upstream IIb/IIIa
RR (95 CI)
lt.001 .93
Net clinical outcome
11.7
11.7
1.00 (0.89-1.11)
Ischemic composite
.06 .13
Upper boundary non-inferiority
7.9
7.1
1.12 (0.97-1.29)
lt.001 .01
Major bleeding
4.9
6.1
0.80 (0.67-0.95)
ITT population
Deferred PCI GPI better
Routine Upstream GPI better
Stone GW et al Presented at 55th ACC Annual
Meeting March 2006
83
ACC/AHA/SCAI PCI Guidelines
Anti-thrombin Therapy

• Class I
• UFH should be given to pts undergoing PCI (Level
  of Evidence C)
• For pts with HIT, it is recommended that
  bivalirudin or argatroban be used (Level of
  Evidence B)

84
ACC/AHA/SCAI PCI Guidelines
Anti-thrombin Therapy

• Class IIa
• It is reasonable to use bivalirudin as an
  alternative to UFH GPI in low-risk pts having
  elective PCI (Level of Evidence B)
• LMWH is a reasonable alternative to UFH in pts
  with UA/NSTEMI under-going PCI (Level of
  Evidence B)

85
ACC/AHA/SCAI PCI Guidelines
Anti-thrombin Therapy

• Class IIb
• LMWH may be considered as an alternative to UFH
  in pts with STEMI undergoing PCI (Level of
  Evidence B)

86
Anti-Thrombins for PCI
Summary

• UFH is effective for PCI, especially when used
  with GP2b3a inhibition
• LMWH (enoxaparin) is safe and effective with PCI
• Bivalirudin is superior to heparin and
  non-inferior to heparin GP 2b3a Rx

87
Anti-Thrombins for PCI
Summary

• UFH is effective for PCI, especially when used
  with GP2b3a inhibition
• LMWH (enoxaparin) is safe and effective with PCI
• Bivalirudin is superior to heparin and
  non-inferior to heparin GP 2b3a Rx

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