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Uninterrupted Warfarin vs. Bridge Therapy with Parenteral Anticoagulation in Acute Coronary Syndrome

Take Home Point(s):

  • For patients taking oral anticoagulant therapy (OAC) and presenting to the emergency department (ED) with acute coronary syndrome (ACS) and have an INR between 2 - 3, controversy exists as to whether to continue OAC or to bridge these patients with heparin, LWMH or bivalrudin.
  • A small number of recent studies compared uninterrupted warfarin therapy to heparin bridge therapy and found no different in endpoints of major adverse cardiac and cerebrovascular events, but did show a trend towards increased bleeding risk in the bridge therapy group.
  • Currently, there is no consensus in the available guidelines and until better evidence becomes available, patients with a high risk for thromboemboli, should not have interruption of warfarin to prevent variability in therapeutic anticoagulation that is concerning for increased bleeding.

Summary:

In acute coronary syndrome (ACS), atherosclerotic plaque rupture and subsequent thrombotic occlusion at the rupture site prevents myocardial perfusion, resulting in tissue ischemia. Once plaque rupture has occurred, the potential for reperfusion is maximized by the initiation of anti-platelet and anti-coagulant medications.  By interrupting both platelet activation and the coagulation cascade, the goal is to prevent fibrin/platelet clot formation and cross-linking. Traditionally, anti-coagulant therapy has targeted the intrinsic pathway of the coagulation cascade, including unfractionated heparin and low molecular weight heparins.

For patients taking oral anticoagulant therapy (OAC) and presenting to the emergency department with ACS and have an INR between 2 - 3, controversy exists as to whether to continue oral anticoagulation or to bridge these patients with traditional parenteral medications. While OACS block either the extrinsic pathway (i.e. warfarin) or the common pathway (i.e. Xa inhibitors) of the coagulation cascade, the end goal of thrombin inhibition is accomplished and theoretically a reasonable alternative. In vivo, however, no two anti-coagulants are alike and further investigation is warranted for the safety profile of each agent in ACS.

While OACs have commonly been held for a week prior to elective surgery, ACS provides a unique circumstance in which therapy must be initiated or maintained in the face of an imminent procedure without time to allow for INR normalization or OAC washout. Studies on the efficacy and safety of uninterrupted OAC in patients presenting with ACS are limited. Heparin-based regimens in ACS have long been the standard of care. With the exception of the SYNERGY trial, which did exclude patients with an INR >1.5, most of the heparin-based studies for ACS did not delineate whether patients on OACs were included.

A small number of more recent studies compared uninterrupted warfarin therapy to heparin bridge therapy and included endpoints of major adverse cardiac and cerebrovascular events and bleeding complications. They found there to be no statistical difference between the two groups, and if anything, there was a trend towards a higher bleeding risk in the bridge therapy group. While these studies were underpowered and mostly retrospective in nature, they do provide a foundation upon which to direct further study and suggest that uninterrupted warfarin therapy may be beneficial and less costly to both the patient and the health system.

In clinical practice, there is no consensus in the available guidelines. Most advocate for the cessation of warfarin therapy in patients with low risk for thromboemboli and re-initiation after PCI plus or minus a heparin bridge. For patients with a high risk for thromboemboli, however, interruption of warfarin should be avoided to prevent variability in therapeutic anticoagulation.  Until high quality evidence becomes available, a balance of risks and benefits must be considered and in the face of new OACs without measurable therapeutic lab values, further investigation is needed to develop encompassing guidelines.

Authors: 

  • Anthony J. Busti, MD, PharmD, FNLA, FAHA
  • Karolina DeAugustinas, MD

Date Last Reviewed:  October 2015

Supporting Guidelines

  • 2014 European Society of Cardiology Working Group on Thrombosis, EHRA, EAPCI, ACCA, HRS, & APHRS: 
    For NSTE-ACS
    "In the ACS setting, patients are often given aspirin, clopidogrel, heparin (whether UFH or enoxaparin) or bivalirudin and/or a GP IIb/IIIa inhibitors. Given the risk of ischaemia and bleeding it may be prudent to stop OAC (i.e. whether NOAC or a VKA) therapy, and where a VKA or NOAC is used, administer UFH or bivalirudin only as bailout (but avoiding GP IIb/IIa inhibitors) or if INR ≤2 in a patient on VKA, balancing the acute need for additional antithrombotic therapy with the excess bleeding risk and the 'thrombus burden' (Class IIb, level of evidence C). (a) in low-risk ACS patients with delayed transfer for an invasive strategy at .24 h of admission, it may be prudent to stop OAC therapy and bridge the patient with unfractionated heparin or enoxaparin (class IIb level of evidence C)."

    For PCI:
    "In the acute setting, a patient with AF and STEMI may be treated with primary PCI, aspirin, clopidogrel, and heparin (UFH) or bivalirudin, while GP IIb/IIIa inhibitors in bailout situations might be useful in some cases. Given the risk of bleeding with such combination antithrombotic therapies, it may sometimes be prudent to temporarily stop OAC therapy. Regular or even 'routine' use of GP IIb/IIIa inhibitors is discouraged, as are the novel P2Y12 inhibitors (Class IIb, level of evidence B). In the setting of STEMI, radial access for primary PCI is the best option to avoid procedural bleeding depending on operator expertise and preference (Class I, level of evidence A)."

    • Reference: Lip GY et al. Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary or valve interventions: a joint consensus document of the European Society of Cardiology Working Group on Thrombosis, European Heart Rhythm Association (EHRA), European Association of Percutaneous Cardiovascular Interventions (EAPCI) and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS). Eur Heart J 2014;35(45):3155-79. PubMed  

    2014 ACC/AHA Guidelines for Atrial Fibrillation: 
    Interruption and Bridging Anticoagulation.
    "Interruption of anticoagulation is often considered for patients with AF who have episodes of bleeding or require surgical or interventional procedures associated with a bleeding risk. There is sparse evidence on which to base specific recommendations on bridging oral anticoagulants among patients with nonvalvular AF with adjusteddose heparin or LMWH.241 .... For patients who are treated with warfarin and who are at low risk of thromboemboli or those who are back in normal sinus rhythm and are undergoing surgical or diagnostic procedures that carry a risk of bleeding, stopping warfarin for up to 1 week and allowing the INR to normalize without substituting UFH is a recognized approach. Warfarin is then resumed after adequate hemostasis has been achieved. For patients at higher risk of thromboembolism (mechanical valves, prior stroke, CHA2DS2-VASc score ≥2), bridging with UFH or LMWH is a common practice, although data for LMWH are limited.22 An increasingly common approach, especially for pacemaker or implantable cardioverter-defibrillator implantation, catheter ablation, coronary angiography, and other vascular interventions, is to perform the procedure without interrupting warfarin. 241,243-247 ... The timing of resumption should take into account the fact that anticoagulation, in contrast to warfarin, is achieved promptly and that reversal agents are not yet available for these agents, which complicates management if bleeding occurs."

    For PCI:
    "In patients undergoing percutaneous coronary intervention, dual antiplatelet therapy with aspirin and clopidogrel is indicated to prevent stent thrombosis. The combination of oral anticoagulants and antiplatelet therapy ("triple therapy") is associated with a high annual risk of fatal and nonfatal bleeding episodes.251-254"

    • Guideline Rating:  NR
    • Reference:  January CT et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. 2014;130(23):e199-267.  PubMed  

    2014 ACC/AHA NSTE-ACS Guidelines: 
    No recommendations related to warfarin bridging or continuation

    • Reference:  Amsterdam EA et al.  2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.  Circulation 2014:[Epub ahead of print]. PubMed

    2013 AHA STEMI Guidelines 
    No recommendations related to warfarin bridging or continuation

    • Reference:O'Gara PT et al.  2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.  Circulation 2013;127(4):e362-425. PubMed

    2012 ACCP CHEST Guidelines 9th Edition: 
    No recommendations related to warfarin bridging or continuation

    • Reference:  Vandvik PO et al.  Primary and secondary prevention of cardiovascular disease. Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. CHEST 2012;141(suppl):e637S-e668S. PubMed

    2010 AHA ACLS Guidelines for Acute Coronary Syndrome: 
    No recommendations related to warfarin bridging or continuation

    • Reference:  O'Connor RE et al. Part 9. Acute Coronary Syndromes: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Circulation 2010;122:S422-S465.  PubMed

Landmark or Original Studies

  • Rubboli A et al. Anti-platelet pre-treatment for atrial fibrillation patients on warfarin referred for coronary angiography/stenting because of non-ST-elevation acute coronary syndrome: an alternative proposal. Int J Cardiol 2015;201:494-496. PubMed
  • Lahtela H et al. Heparin bridging vs. uninterrupted oral anticoagulation in patients with Atrial Fibrillation undergoing Coronary Artery Stenting. Results from the AFCAS registry. Circ J 2012:76(6):1363-8. PubMed
  • Karjalainen PP et al. Safety of percutaneous coronary intervention during uninterrupted oral anticoagulant treatment. Eur Heart J 2008;29(8):1001-10. PubMed
  • Jessup DB et al. Elective coronary angiography and percutaneous coronary intervention during uninterrupted warfarin therapy. Catheter Cardiovasc Interv 2003;60(2):180-4. PubMed

Supporting Studies

  • Feng L et al. Oral anticoagulation continuation compared with heparin bridging therapy among high risk patients undergoing implantation of cardiac rhythm devices: a meta-analysis. Thromb Haemost 2012;108(6):1124-31. PubMed

Related Articles & Reviews

  • TsuLV et al.  Safety of new oral anticoagulants with dual antiplatelet therapy in patients with acute coronary syndromes. Ann Pharmacother 2013;47:573-7. PubMed

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