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

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

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

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

NSTE-ACS Net Clinical Benefit of Anticoagulants

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

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

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

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

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 1464-76

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;354:1464-76

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 = 0.055. 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. 2006 ;48:1326-35 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 = 0.0067). 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.

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 (4.59-5.62); at day 180: 3.16 (2.92-3.44) 30 60 90 120 150 180 Days Budaj et al. JACC 2006;abstract 972-224

Bleeding Rates: Day 9 Outcome Enox (%) Fonda HR (95% CI) P value No. Randomized 10021 10057 Total Bleed 7.3 3.3 0.44 (0.39-0.50) <<0.0001 Major Bleed 4.1 2.2 0.52 (0.44-0.61) TIMI Major Bleed 1.3 0.7 0.55 (0.41-0.74) Minor Bleed 3.2 1.1 0.35 (0.28-0.43)

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

OASIS-5

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 2009 30:1457-1466 23

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

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

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 < 0.0001] and Xa clot time [64.9 s (SD 17.7 s) vs. 111.8 s (SD 29.6 s), P < 0.0001], and significantly higher ETP area under the curve (AUC) [386.7 mA (SD 51.5 mA) vs. 206.4 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 < 0.001 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

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

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

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;354:1464-76

Fondaparinux in PCI

Clinical Events after PCI: Day 30

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

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

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

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

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

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

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

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

Coronary Angiography/PCI to be performed within 72 hours Study Design Adjunctive therapy during PCI NSTEACS Fonda 2.5 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

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

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%

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 0.54-1.19 0.27

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 0.54-1.19 0.27 Components of primary outcome (Peri-PCI) Major bleeds 1.2% 1.4% 1.14 0.53-2.49 0.73 Minor bleeds 1.7% 0.7% 0.40 0.16-0.97 0.04 Major vascular access site complications 4.3% 3.2% 0.74 0.47-1.18 0.21

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 1.00-2.28 0.05 Death, MI, TVR 2.9% 4.5% 1.58 0.98-2.53 0.06 Death 0.6% 0.8% 1.31 0.45-3.78 MI 2.5% 3.0% 1.22 0.72-2.08 TVR 0.3% 0.9% 2.95 0.80-10.9 Stent thrombosis 0.5% 1.2% 2.36 0.83-6.73 0.11 Catheter thrombosis 0.1% 0.5%* 4.91 0.57-42.1 0.15 * One event occurred during coronary angiography after randomization

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 0.64-2.23, p=0.57) 0.03 Low dose 4.5% vs. Standard dose 2.9% HR 1.56 (95% CI 0.98-2.48, 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

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% (0.6-2.1) 1.5% 3.6% FUTURA low dose UFH 1.2 % (0.6-2.2) Adding unfractionated heparin during PCI to fondaparinux does not appear to increase peri-PCI major bleeding *Major bleeding rates within 48 hours following PCI

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

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

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

ESC Guidelines European Heart Journal doi:10.1093/eurheart/ehr236

(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:10.1093/eurheart/ehr236

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:10.1093/eurheart/ehr236

Recommendation for Invasive evaluations and revascularization ESC Guidelines European Heart Journal doi:10.1093/eurheart/ehr236

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

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