1 / 56

Dramatic Improvement of Outcome over the Last 30 years

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

tod
Télécharger la présentation

Dramatic Improvement of Outcome over the Last 30 years

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. OASIS in ACS: with Updates on 2011 ESC Guidelines on AnticoagulationDonato 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 Prothrombin Fondaparinux LMWH Heparin AT Factor Xa Conformational activation of GPIIb/IIIa GPIIb/IIIa inhibitors AT Thrombin Platelet aggregation Bivalirudin Hirudin Dabigatran Fibrinogen Fibrin Thrombus

  5. NSTE-ACSNet ClinicalBenefit of Anticoagulants

  6. ROADMAP TO UA/NSTEMIEarly 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/NSTEMIEarly 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

  8. 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

  9. 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

  10. 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 Enoxaparin 1 mg/kg s.c. bid for 2-8 days 1 mg/kg s.c. od if ClCr<30mL/min Fondaparinux 2.5 mg s.c. od up to 8 days 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

  11. Study Objectives and Outcomes • Objectives • 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 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

  12. 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 Key Messages from OASIS 5

  13. Increased Mortality at Days 30/180 in Patientswith Major Bleeds by Day 9 in OASIS 5 Maj Bleed 9 days Cumulative Hazard No Maj Bleed 9 days Adjusted HR (95% CI) at day 30: 5.06 (4.59-5.62); at day 180: 3.16 (2.92-3.44) 0 30 60 90 120 150 180 Days Budaj et al. JACC 2006;abstract 972-224

  14. Bleeding Rates: Day 9

  15. Categories of Major Bleeds at 9 Days

  16. OASIS-5

  17. 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 0.5 1 2 4 8 Hazard ratio (95%CI) Mehran, R. et al. Eur Heart J 2009 30:1457-1466

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

  19. 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

  20. Comparison of Anticoagulant Activities of Enoxaparin and Fondaparinux in OASIS 5 Anderson J. J Thromb Haemostasis 2010; 8: 243-9

  21. OASIS 5 Enoxaparin vs Fondaparinux ETP AUC, endogenous thrombin potential area under the curve J Eikelboom, in press

  22. A New Concept isBorn • 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

  23. 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

  24. Fondaparinux in PCI

  25. Clinical Events after PCI: Day 30 P=0.004 P=0.60 P<0.0001 P=0.68

  26. 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

  27. Catheter-Related Thrombus with Enoxaparin and Fondaparinux Enoxaparin • 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 caseof catheter thrombus was reported Mean dose of UFH for PCI used in OASIS 5: 47 IU/kg

  28. Adding UFH to Fondaparinux for PCI is Safe and Preserves the Lower Bleeding with Fondaparinux Mean dose of UFH for PCI used in OASIS 5: 47 IU/kg Yusuf S. et al. N Engl J Med. 2006;354:2829

  29. 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

  30. 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

  31. Simple Transition of Patients Initiated on Fondaparinux to the Catheterization Lab 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 OASIS 5 *May perform cath>6 hours after last subcut dose if this was center’s usual practice with using LMWH

  32. 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

  33. 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

  34. Study Design Adjunctive therapy during PCI 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

  35. Study Outcome Definitions

  36. Baseline and Procedural Characteristics

  37. Primary Outcome at 48 h

  38. Primary Outcome at 48 h

  39. Secondary Outcomes at 30 days * One event occurred during coronary angiography after randomization

  40. Outcomes to 30 days 0.05 Major Bleed at 30 days Death/MI/TVR at 30 days 0.04 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 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 0.02 0.01 Standard Dose Low Dose 0.0 0.01 Standard Dose 0 0 3 3 6 6 9 9 12 12 15 15 18 18 21 21 24 24 27 27 30 30 Low Dose No. at Risk Days Standard Dose 1002 980 975 975 974 971 0.0 Low Dose 1024 997 988 982 981 978 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 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 Standard Dose 1002 986 981 980 980 978 Low Dose 994 1024 1002 1001 998 997

  41. Comparison to OASIS 5 Major Bleeding • Adding unfractionated heparin during PCI to fondaparinux does not appear to increase peri-PCI major bleeding *Major bleeding rates within 48 hours following PCI

  42. 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

  43. 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

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

More Related