1. OASIS in ACS: with Updates on 2011 ESC Guidelines on Anticoagulation Donato Maranon, MD, FPCP, FPCC, FACC

2. Dramatic Improvement of Outcome over the Last 30 years
Antiplatelet agents
Anticoagulants
Revascularization / Reperfusion / Thrombolysis
Long term treatment / secondary prevention
Implementation of guidelines

3. Therapeutic Options in Acute Coronary Syndromes
Anti-ischemic treatment
Antiplatelet agents
Anticoagulants
Revascularization/Reperfusion/Thrombolysis
Long term treatment/secondary prevention

4. Targets for antithrombotics
Tissue factor
Collagen
Aspirin
Plasma clotting
cascade
ADP
Direct Xa inhib
Thromboxane A2
Clopidogrel
Prasugrel
AZD 6140
Fondaparinux
LMWH
Heparin
Prothrombin AT
Factor Xa
Conformational activation of GPIIb/IIIa AT
GPIIb/IIIa
inhibitors
Thrombin
Platelet aggregation
Bivalirudin
Hirudin
Dabigatran
Although there are a variety of approaches to enhancing anticoagulant effects none are completely satisfactory when used as a single agent.
Major categories of anticoagulant therapy include agents that target any one of three main components of the thrombotic process; thrombin, platelets, or fibrin.
Fibrinogen
Fibrin
Thrombus 4

5. NSTE-ACS Net Clinical Benefit of Anticoagulants

6. ROADMAP TO UA/NSTEMI Early Conservative Strategy
Bedrest, O2 if indicated
Nitrates, Morphine, BB, ACEi
Aspirin, Clopidogrel
LMWH or UFH or Fondaparinux
Monitor with serial ECG and cardiac biomarkers
Eptifibatide or Tirofiban, if with continuing ischemia, elevated TnT or TnI, and other high risk factors

7. ROADMAP TO UA/NSTEMI Early Invasive Strategy
Bedrest, O2 if needed
Nitrates, Morphine, BB, ACEi
Aspirin, LMWH or UFH
GP IIb/IIIa, tirofiban, eptifibatide, or abciximab is added to aspirin, clopidogrel and heparin if PCI needed

9. Guidelines Recommendations for Anticoagulation
Anticoagulation is recommended for all patients in addition to antiplatelet therapy (I-A)
Anticoagulation should be selected according to the risk of both ischaemic and bleeding events (I-B)
Several anticoagulants are available, namely UFH, LMWH, Fondaparinux, bivalirudin. The choice depends on the initial strategy (urgent invasive, early invasive, or conservative strategies (I-B)
In an urgent invasive strategy UFH (I-C), or enoxaparin (IIa-B) or bivalirudin (I-B) should be immediately started
2007 ESC Guidelines

10. Guidelines Recommendations for Anticoagulation
In a non-urgent situation, as long as decision between early invasive or conservative strategy is pending:
Fondaparinux is recommended on the basis of the most favourable efficacy/safety profile (I-A)
Enoxaparin with a less favourable efficacy/safety profile than fondaparinux should be used only if the bleeding risk is low (IIa-B)
As efficacy/safety profile of LMWH (other than enoxaparin) or UFh relative to fondaparinux is unknown; these anticoagulants cannot be recommended over fondaparinux (IIa-B)
2007 ESC Guidelines

11. OASIS 5: An International, Multicenter, Randomized, Double-Blind, Double-Dummy Trial in 41 Countries
20,078 patients with UA/NSTEMI
Aspirin, Clopidogrel, anti-GPIIb/IIIa, planned Cath/PCI as per local practice
Randomization
Fondaparinux
2.5 mg s.c. od up to 8 days
Enoxaparin
1 mg/kg s.c. bid for 2-8 days
1 mg/kg s.c. od if ClCr<30mL/min
OASIS 5 was a randomized, double-blind, double-dummy trial in 20,078 patients with UA/NSTEMI in 576 centers in 41 countries
Patients were eligible if they presented to hospital with symptoms of UA or MI without persistent ST elevation and at least two of the following additional criteria: age >60 years, troponin T or I or CK-MB above the upper limit of normal or ECG changes compatible with ischemia (i.e., ST depression at least 1 mm in two contiguous leads or T-wave inversion >3 mm or any dynamic ST shift or transient ST elevation).
Exclusion criteria were:
Age < 21 years
Any contra-indication to enoxaparin
Hemorragic stroke <12 months
Creatinine >3 mg/dL or 265 µmol/L
Fondaparinux was given for 8 days or until hospital discharge (if earlier), and enoxaparin was given for 2-8 days or until the patient was clinically stable, as per its current approval for use in UA and NSTEMI. The minimum duration of therapy was two days. However, catheterization and PCI could be scheduled earlier than this time if necessary. Blinded study drugs were continued through the PCI procedure.
Vital status ascertained in 20,066 (99.9%)
Lost to follow-up at day 9: fondaparinux: n=7 and enoxaparin: n=5
1. Michelangelo OASIS 5 Steering Committee. Am Heart J 2005;150:1107.e1-.e10
2. OASIS 5 Investigators. N Engl J Med

12. Study Objectives and Outcomes
Primary efficacy objective: To demonstrate non-inferiority of fondaparinux compared with enoxaparin
Primary safety objective: To determine whether fondaparinux was superior to enoxaparin in preventing major bleeding
Outcomes (centrally adjudicated)
Primary efficacy: 1st occurrence of the composite of death, MI, or refractory ischemia (RI) up to day 9
Primary safety: Major bleeding up to day 9
Risk benefit: Death, MI, refractory ischemia, major bleeds up to day 9
Secondary: Above & each component separately at days 30 and 180
The primary efficacy objective was to demonstrate the non-inferiority of fondaparinux compared with enoxaparin. The primary safety objective was to determine whether fondaparinux was superior to enoxaparin in preventing major bleeding.
The primary efficacy outcome was the composite of death, MI, or refractory ischemia up to day 9. Patients were followed up for a minimum of 90 days and a maximum of 180 days.
Pre-specified secondary outcomes included: a) death or MI; b) death, MI or refractory ischemia; c) the individual components of the above composites at 30 days and study end. Information on strokes was also systematically collected. The primary safety outcome was major bleeding up to Day 9.
All events were adjudicated by a blinded committee. The balance of benefit and risk was assessed on the basis of the adjudicated primary efficacy and safety outcomes.
1. Michelangelo OASIS 5 Steering Committee. Am Heart J 2005;150:1107.e1-.e10
2. OASIS 5 Investigators. N Engl J Med 2006;354:

13. Key Messages from OASIS 5
Major bleeding risk reduction
Significant risk reduction for death and death/ MI/ stroke 30 days and 6 months
Consistent effect in every subset of patients
PCI
Elderly
Renal failure
Irrespective of initial risk category
Excess of catheter thrombus formation during PCI
Figure 2. (Panel A) Odds ratios for death with rescue angioplasty versus conservative approach within the first 30 days after randomization. The incidence of death rate was lower in the rescue group than in the conservative group. Overall odds ratio 0.63; 95% confidence interval (CI), 0.39 to 1.01; p = The analysis for heterogeneity was nonsignificant (p = 0.53).
LIMI = LImburg Myocardial Infarction trial; MA = meta-analysis; MERLIN = Middlesbrough Early Revascularisation to Limit INfarction; PCI = percutaneous coronary intervention; PTCA = percutaneous transluminal coronary angioplasty; REACT = Rescue Angioplasty Versus Conservative Therapy or Repeat Thrombolysis Trial; RESCUE = Randomized Evaluation of Salvage Angioplasty with Combined Utilization of Endpoints.
Percutaneous coronary intervention after fibrinolysis: a multiple meta-analyses approach according to the type of strategy. Collet JP, Montalescot G, Le May M, Borentain M, Gershlick A.
J Am Coll Cardiol ;48:
OBJECTIVES: We performed a meta-analysis of randomized trials that enrolled ST-segment elevation myocardial infarction patients treated with fibrinolysis to assess the potential benefits of: 1) rescue percutaneous coronary intervention (PCI) versus no PCI; 2) systematic and early (< or =24 h) PCI versus delayed or ischemia-guided PCI; 3) fibrinolysis-facilitated PCI versus primary PCI alone. BACKGROUND: The impact of PCI strategies after fibrinolysis on mortality or reinfarction remains to be established. METHODS: The meta-analysis was performed using the odds ratio (OR) as the parameter of efficacy with a random effect model. Fifteen randomized trials (5,253 patients) were selected. The primary end point was mortality or the combined end point of death or reinfarction. RESULTS: Rescue PCI for failed fibrinolysis reduced mortality (6.9% vs. 10.7%) (OR, 0.63; 95% confidence interval [CI], 0.39 to 0.99; p = 0.055) and the rate of death or reinfarction (10.8% vs. 16.8%) (OR, 0.60; 95% CI, 0.41 to 0.89; p = 0.012) compared with a conservative approach. Systematic and early PCI performed during the "stent era" led to a nonsignificant reduction in mortality compared with delayed or ischemia-guided PCI (3.8% vs. 6.7%) (OR, 0.56; 95% CI, 0.29 to 1.05; p = 0.07) and to a 2-fold reduction in the rate of death or reinfarction (7.5% vs. 13.2%) (OR, 0.53; 95% CI, 0.33 to 0.83; p = ). This benefit contrasted with a nonsignificant increase in the rate of both mortality (5.5% vs. 3.9%, p = 0.33) or death or reinfarction (9.6% vs. 5.7%, p = 0.06) observed in the "balloon era." Fibrinolysis-facilitated PCI was associated with more reinfarction as compared with primary PCI alone (5.0% vs. 3.0%) (OR, 1.68; 95% CI, 1.12 to 2.51; p = 0.013) without significant impact on mortality (OR, 1.30; 95% CI, 0.92 to 1.83; p = 0.13). CONCLUSIONS: Our findings support rescue PCI and systematic and early PCI after fibrinolysis. However, the current data do not support fibrinolysis-facilitated PCI in lieu of primary PCI alone.

18. Increased Mortality at Days 30/180 in Patients with Major Bleeds by Day 9 in OASIS 5
Maj Bleed 9 days
Cumulative Hazard
No Maj Bleed 9 days
The same observations were made in Oasis-5. A four- to five-fold increase in the risk of death, MI and stroke was observed at 30 days and 6 months in patients with bleeding, compared to those without.
Adjusted HR (95% CI) at day 30: 5.06 ( ); at day 180: 3.16 ( ) 30 60 90
120
150
180
Days
Budaj et al. JACC 2006;abstract

19. Bleeding Rates: Day 9 Outcome Enox (%) Fonda HR (95% CI) P value
No. Randomized
10021
10057
Total Bleed
7.3
3.3
0.44 ( )
<<0.0001
Major Bleed
4.1
2.2
0.52 ( )
TIMI Major Bleed
1.3
0.7
0.55 ( )
Minor Bleed
3.2
1.1
0.35 ( )

20. Categories of Major Bleeds at 9 Days
Enox
(No. Pts)
Fonda P
No. Rand.
10021
10057
Total Bleeding
412 (4.1%)
217 (2.2%)
<<0.0001
Intracranial 7
Surgery req’d to stop bleed 77 41
0.0001
Retroperitoneal 37 9
Hb  3 g/dL
312
150
Transfusion  2 units
287
164

22. OASIS-5

23. Impact of Major Bleeding, Re-MI and Transfusion on risk of Death: ACUITY trial
Hazard Ratio (95% CI)
Deaths
P value
Myocardial infarction
3.1 (2.4 to 3.9) 77
<0.001
Major bleeding
3.5 (2.7 to 4.4) 93
<0.001
Blood transfusion
4.5 (3.4 to 5.9) 70
<0.001
Aims: To evaluate the associations of myocardial infarction (MI) and major bleeding with 1-year mortality. Both MI and major bleeding predict 1-year mortality in patients presenting with acute coronary syndrome (ACS). However, the risk of each of these events on the magnitude and timing of mortality has not been well studied.
0.5 1 2 4 8
Hazard ratio (95%CI)
Mehran, R. et al. Eur Heart J : 23

24. OASIS-5 Less Bleeding = Less Deaths
Bleeding Reduced by 50%
Deaths Reduced by 17%
Yusuf S, Mehta S, et al. OASIS-5 Investigators NEJM 2006

25. A Shift in the Paradigm
Fondaparinux makes it possible to reduce both ischemic risk (death, death/MI, death/MI/stroke) and bleeding risk
First ever observed with an anticoagulant in ACS

26. Comparison of Anticoagulant Activities of Enoxaparin and Fondaparinux in OASIS 5
Summary. Background: In the OASIS-5 trial, fondaparinux
reduced major bleeding with similar short-term efficacy as
enoxaparin but lowered death and stroke during long-term
follow-up. The mechanism of lower bleeding and improved
efficacy with fondaparinux is uncertain. Methods and Results:
Wecompared the anti-Xa concentration (reflecting drug levels),
Xa clot time (reflecting anticoagulant effect) and endogenous
thrombin potential (ETP; a global test of hemostatic function)
in plasma samples collected 6, 24 and 72 h after the first dose of
the study drug in 48 patients randomly assigned fondaparinux
2.5 mg day)1 and 42 patients assigned enoxaparin 1 mg kg)1
twice daily in the OASIS-5 trial. Patients assigned to fondaparinux
compared with enoxaparin had a significantly lower mean
anti-Xa level [0.52 IU mL)1 (SD 0.22 IU mL)1) vs. 1.2
IU mL)1 (SD 0.45 IU mL)1), P < ] and Xa clot
time [64.9 s (SD 17.7 s) vs s (SD 29.6 s), P < ],
and significantly higher ETP area under the curve (AUC)
[386.7 mA (SD 51.5 mA) vs mA (SD 90.6 mA),
P < 0.001] at 6 h, and these differences remained evident at
24 and 72 h. There was significantly less variability of the results
of anti-Xa levels, Xa clot time and ETP AUC for fondaparinux
compared with enoxaparin at 6 h (P < for each
comparison). Conclusion: Fondaparinux 2.5 mg day)1 compared
with enoxaparin 1 mg kg)1 twice daily produces less
variable anticoagulant effect and lower mean anticoagulant
intensity. These results most likely explain the reduced risk of
bleeding seen with fondaparinux compared with enoxaparin in
the OASIS-5 trial and suggest that a lower intensity of
anticoagulation than used in the past may be sufficient to
prevent recurrent ischemic events and death in patients
with ACS who are concurrently treated with aspirin and
clopidogrel.
Anderson J. J Thromb Haemostasis 2010; 8: 243-9

27. Enoxaparin vs Fondaparinux
OASIS 5
Enoxaparin vs Fondaparinux
Enoxaparin (n=42)
Fondaparinux (n=48)
P-value
Mean SD
6hr anti-Xa (IU/ml)
1.2
0.45
0.5
0.2
<0.0001
6hr Xa-clot (seconds)
111.8
29.6
64.9
17.7
<0.001
6hr ETP AUC (mA)
206.4
90.6
386.7
51.5
ETP AUC, endogenous thrombin potential area under the curve
J Eikelboom, in press

28. A New Concept is Born
Bleeding carries a high risk of death, MI and stroke
Rate of major bleeding is as high as the rate of death at the acute phase of NSTE-ACS
Prevention of bleeding is equally as important as prevention of ischemic events and results in a significant risk reduction for death, MI and stroke
Risk stratification for bleeding should be part of the decision making process

29. OASIS 5 Conclusions Patients Undergoing PCI
A lower incidence of vascular access site complications was observed with fondaparinux
Fewer bleeding complications with fondaparinux irrespective of the timing of last study drug administration
Fewer bleeding complications with fondaparinux irrespective of the use of UFH prior to PCI
A higher rate of guiding catheter thrombosis was observed with fondaparinux when PCI was performed without UFH, but this was largely avoided if UFH was used just before/during the procedure
OASIS 5 Investigators. N Engl J Med 2006;354:

30. Fondaparinux in PCI

31. Clinical Events after PCI: Day 30

32. Vascular Access Site Complications, Large Hematomas and Pseudo-aneurysms
HR 0.41
P<<0.0001
HR 0.36
P<<0.0001
HR 0.63
P=0.033

33. Catheter-Related Thrombus with Enoxaparin and Fondaparinux
8 cases total: 6 when PCI performed within 6 h of last enox dose where no UFH was given
Rate is 6/1431=0.42%
In Enoxaparin patients receiving study UFH, there was 1 case.
1 case time of PCI not ascertained
Fondaparinux
29 cases (UFH was not routinely given to fonda group)
Rate is 29/3135=0.9%
When open label UFH was used prior to PCI (5000 U mean), only 1 case of catheter thrombus was reported
Mean dose of UFH for PCI used in OASIS 5: 47 IU/kg

34. Adding UFH to Fondaparinux for PCI is Safe and Preserves the Lower Bleeding with Fondaparinux
Enox
Fonda HR CI
No UFH post-Randomization
1.2
(n=1,277)
0.5
(n=1,313)
0.45
0.18–1.11
UFH or equivalent placebo mandated by protocol during PCI
1.1
(n=1,229)
0.4
(n=1,279)
0.34
0.12–0.95
Open Label UFH
2.7
(n=598)
1.3
(n=543)
0.48
0.20–1.17
Overall
1.5
(n=3,104)
0.6
(n=3,135)
0.42
0.24–0.71
Mean dose of UFH for PCI used in OASIS 5: 47 IU/kg
Yusuf S. et al. N Engl J Med. 2006;354:2829 34

35. OASIS 5 PCI: Net Clinical Benefit Favours Fondaparinux in Invasively Managed Patients
Death/MI/Stroke/Major Bleeding
RR 0.78
P=0.004
RR 0.76
P=0.035
Mehta et al. JACC 2006;abstract 821-5
Mehta et. al. JACC 2007, in press

36. Conclusions for PCI
Patients who underwent an early invasive strategy in OASIS 5 trial had superior net benefit with fondaparinux compared to enoxaparin
Fondaparinux is safe and effective as upstream therapy in patients undergoing PCI and reduces bleeding by half compared to enoxaparin
Catheter thrombus occurs very rarely in comparison with death or re-MI and appears to be avoided with standard UFH for the PCI itself without increasing major bleeding
Adjunctive UFH (50 IU/kg) with or without GP IIb/IIIa antagonist is recommended as PCI anticoagulation

37. Proceed to Cath Lab as usual*
Simple Transition of Patients Initiated on Fondaparinux to the Catheterization Lab
OASIS 5
Treat with ASA, clopidogrel and fondaparinux, +/- IV glycoprotein IIb/IIIa inhibitor in the ER
Proceed to Cath Lab as usual*
If PCI needed, give UFH (dose 50 units/kg) +/- glycoprotein IIb/IIIa inhibitor
Post procedure, follow usual practice for sheath removal. Immediate removal if closure device or radial and 6 hours after last fondaparinux subcut dose if no closure device used
*May perform cath>6 hours after last subcut dose if this was center’s usual practice with using LMWH

38. Sanjit S. Jolly on behalf of FUTURA/OASIS 8 Trial Group
Low vs. Standard Dose Unfractionated Heparin for Percutaneous Coronary Intervention in Acute Coronary Syndromes Patients treated with Fondaparinux: the FUTURA/OASIS 8 Randomised Trial
Sanjit S. Jolly on behalf of FUTURA/OASIS 8 Trial Group

39. FUTURA Trial Study Objectives
Primary Objective: To determine whether Low fixed dose vs. Standard ACT guided unfractionated heparin during PCI reduces the composite of peri-PCI* major, minor bleeding and vascular access site complications in ACS patients treated with fondaparinux
Secondary Objective: To determine if major bleeding rates in FUTURA (with unfractionated heparin added to fondaparinux) are higher than OASIS 5 PCI (with Fondaparinux used alone)
*Peri-PCI defined within 48 hours following PCI

40. Coronary Angiography/PCI to be performed within 72 hours
Study Design
Adjunctive therapy
during PCI
NSTEACS
Fonda mg sc
Angio No PCI
30 Day Follow-Up
Angio with PCI R
Std Dose UFH
(85 U/kg or 60 U/kg with GP IIb/IIIa)
ACT guided*
Low Dose UFH
(50 U/kg irrespective of GP IIb/IIIa) –
without ACT
Coronary Angiography/PCI to be performed within 72 hours
Double
Blind
With at least 2 of following:
Age>60
elevated biomarkers
ECG changes
Patients were not eligible if required urgent coronary angiography (<120 min) due to clinical instability
Registry
*ACT Targets consistent with current guidelines

41. Study Outcome Definitions
Major Bleeding (OASIS 5)
Fatal
Symptomatic ICH
Retroperitoneal hemorrhage
Intraocular bleeding leading to significant vision loss
Requiring surgical intervention
Hb drop of ≥3 g/dL
Blood transfusion of > two units RBCs
Minor Bleeding
Any other significant bleeding leading to transfusion of one unit of blood or discontinuation of antithrombotic therapy.
Major Vascular Access Site Complications
Large hematoma (≥5 cm or requiring intervention)
Pseudoaneurysm requiring treatment
Arterio-venous fistula
Other vascular surgery related to the access site

42. Baseline and Procedural Characteristics
Standard Dose UFH
N=1002
Low Dose UFH
N=1024
Age (years)
65.5
65.3
Male (%)
68.5
67.3
Diabetes (%)
27.9
26.1
ECG changes (%)
74.6
75.3
Elevated Troponin I or T (%)
78.8
81.3
Aspirin (%)
96.1
95.4
Clopidogrel (%)
96.3
94.6
Procedural GP IIb/IIIa (%)
26.4
25.8
Femoral Access (%)
62.4
64.2
Any Stents placed (%)
94.0
93.7
Baseline characteristics are well balanced between the groups. This was a high risk populations with mean age of 65, more than a quarter with diabetes, three quarter with ECG changes and 80% biomarker positive. The rate of GP IIb IIIa was 26%

43. Primary Outcome at 48 h OR 95% CI P
Standard Dose UFH (n=1002)
Low
Dose UFH (n=1024) OR
95% CI P
Peri-PCI major, minor bleeds and vascular access complications
5.8%
4.7%
0.80
0.27

44. Primary Outcome at 48 h OR 95% CI P
Standard Dose UFH (n=1002)
Low
Dose UFH (n=1024) OR
95% CI P
Peri-PCI major, minor bleeds and vascular access complications
5.8%
4.7%
0.80
0.27
Components of primary outcome (Peri-PCI)
Major bleeds
1.2%
1.4%
1.14
0.73
Minor bleeds
1.7%
0.7%
0.40
0.04
Major vascular access site complications
4.3%
3.2%
0.74
0.21

45. Secondary Outcomes at 30 days
Standard Dose UFH (n=1002)
Low
Dose UFH (n=1024) OR
95% CI P
Key Secondary outcome:
Peri-PCI major bleeding, death, MI, TVR
3.9%
5.8%
1.51
0.05
Death, MI, TVR
2.9%
4.5%
1.58
0.06
Death
0.6%
0.8%
1.31 MI
2.5%
3.0%
1.22
TVR
0.3%
0.9%
2.95
Stent thrombosis
0.5%
1.2%
2.36
0.11
Catheter thrombosis
0.1%
0.5%*
4.91
0.15
* One event occurred during coronary angiography after randomization

46. Outcomes to 30 days
Major Bleed at 30 days
Death/MI/TVR at 30 days
Days 3 6 9 12 15 18 21 24 27 30
0.0
0.01
0.02
0.03
0.04
0.05
Standard Dose
Low Dose
No. at Risk
1002
986
981
980
978
1024
1001
998
997
994
0.05
0.04
Low dose 2.2% vs. Standard dose 1.8%,
HR 1.20 (95% CI , p=0.57)
0.03
Low dose 4.5% vs. Standard dose 2.9%
HR 1.56 (95% CI , p=0.06)
0.02
0.01
Standard Dose
Low Dose
0.0 3 3 6 6 9 9 12 12 15 15 18 18 21 21 24 24 27 27 30 30
No. at Risk
Days
Standard Dose
1002
980
975
975
974
971
Low Dose
1024
997
988
982
981
978
Subgroup analysis showed consistent results for primary outcome and for death/MI/TVR for pre-specified subgroups of: Age, Sex,
GP IIb/IIIa, BMI, CrCl, Arterial access site

47. Comparison to OASIS 5 Major Bleeding
Adjusted
Major bleeding* rate (95% CI)
OASIS 5 PCI Fondaparinux
Major bleeding*
OASIS 5 PCI
Enoxaparin
FUTURA standard dose UFH
1.1% ( )
1.5%
3.6%
FUTURA low dose UFH
1.2 % ( )
Adding unfractionated heparin during PCI to fondaparinux does not appear to increase peri-PCI major bleeding
*Major bleeding rates within 48 hours following PCI

48. Conclusions
No significant difference in major/minor bleeding or vascular complications between Low fixed dose and Standard dose unfractionated heparin
While low dose heparin reduced minor bleeding there was a trend towards reduced efficacy
The use of unfractionated heparin for PCI on a background of fondaparinux did not increase major bleeding when compared to fondaparinux alone and lower than that previously observed with enoxaparin

49. Implications
ACS patients treated with fondaparinux can undergo PCI safely with unfractionated heparin
No evidence to depart from guideline recommended standard dose regimen of unfractionated heparin during PCI
Adding unfractionated heparin during PCI to fondaparinux preserves the benefits and safety of fondaparinux (ie. reduced bleeding) while minimizing catheter thrombus

50. Highlights of the Latest European Society of Cardiology Guidelines on Anticoagulants
ESC Guidelines 2011
European Heart Journal

51. ESC Guidelines
European Heart Journal doi: /eurheart/ehr236

52. (2.5mg subcutaneously daily)
ESC 2011 Guidelines in ACS in patients without presenting persistent ST-segment elevation
Fondaparinux
(2.5mg subcutaneously daily)
is recommended as having the most favourable efficacy – safety profile with respect to anticoagulation
GRADE 1 A
ESC Guidelines
European Heart Journal doi: /eurheart/ehr236

53. Contraindicated in severe renal failure (CrCl<20mL/min).
ESC 2011 Guidelines in ACS in patients without presenting persistent ST-segment elevation
Fondaparinux
Contraindicated in severe renal failure (CrCl<20mL/min).
Drug of choice in patients with moderately reduced renal function (CrCl 30 – 60 mL/min)
ESC Guidelines
European Heart Journal doi: /eurheart/ehr236

54. Recommendation for Invasive evaluations and revascularization
ESC Guidelines
European Heart Journal doi: /eurheart/ehr236

55. How Should Fondaparinux Be Used in Patients with UA/NSTEMI?
Administer fondaparinux (2.5 mg sc od) for up to 8 days or until hospital discharge if earlier
If a patient needs to undergo an invasive procedure during the treatment period, the following is recommended:
PCI: UFH should be used during the procedure
CABG surgery: fondaparinux where possible should not be given during the 24 h before surgery and may be restarted 48 h post- operatively

56. THANK YOU