Warfarin Bridging

JENNY CHANUNIVERSITY OF WASHINGTONPHARMD CANDIDATE C/O 2015SWEDISH FAMILY MEDICINE

CLINIC04/30/15

To Clot or Not to Clot?

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ROADMAP

Risk Stratification for Low, Moderate and High Risk Patients

Bridging for Low, Moderate and High Risk Bleeding Procedures

Managing Subtherapeutic INR

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WHO SHOULD RECEIVE BRIDGING?

High Risk Patients: YesModerate Risk Patients: Maybe NOTLow Risk Patients: No

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RISK STRATIFICATION AND RECOMMENDATIONS FOR BRIDGE THERAPY—HIGH RISK

UWMC Anticoagulation Clinic Feb 2014. http://depts.washington.edu/anticoag/home/content/risk-stratification-and-recommendations-bridge-therapy

http://depts.washington.edu/anticoag/home/content/risk-stratification-and-recommendations-bridge-therapy

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RISK STRATIFICATION AND RECOMMENDATIONS FOR BRIDGE THERAPY—MODERATE RISK



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RISK STRATIFICATION AND RECOMMENDATIONS FOR BRIDGE THERAPY—LOW RISK



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WHEN TO BRIDGE

Low Risk Bleeding Procedures

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Scenario 1

A patient arrives to the ACC and you check their INR. It is 2.8. The patient mentions that they have a upcoming root canal next week and their dentist told them to stop warfarin for 5 days before the procedure.

Is this appropriate? What would you advise?

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Bridging for Minor Procedures

Procedure Bridging recommendationLOW BLEEDING RISK

Minor dental procedures• 1 tooth extraction• Routine cleaning• Endodontic (root

canal) procedures

• Either continue warfarin at normal dose or stop 2-3 days before the procedure.

• 2012 CHEST guidelines also recommend the use of a prehemostatic agent such as tranexamic acid with the continuation of warfarin (Grade 2C)

Douketis et al. Perioperative Management of antithrombotic therapy. Chest [Internet]. 2012 Feb [cited 2015 April 21]. 141(2 Suppl):e326S-50S. doi: 10.1378/chest.11-2298

10Bridging for minor procedures

Procedure Bridging Recommendation

MODERATE BLEEDING RISK*• Subgingival scaling• Restorations with

subgingival preparations• Standard root canal

Interruption of warfarin therapy is not necessary. Use local measures to prevent or control bleeding.

HIGH BLEEDING RISK*• Multiple extractions• Apicoectomy (root

removal)• Alevolar surgery (bone

removal)

May need to reduce INR or return to normal hemostasis. Use local methods to prevent or control bleeding.

*UWMC Anticoagulation Clinic. http://depts.Washington.edu/anticoag/home/content/suggestions-anticoagulation-management-and-after-dental-procedures

http://depts.washington.edu/anticoag/home/content/suggestions-anticoagulation-management-and-after-dental-procedures

http://depts.washington.edu/anticoag/home/content/suggestions-anticoagulation-management-and-after-dental-procedures

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Scenario 2

A surgeon from the optometry department calls you in the ACC clinic and asks, “I have a patient on dabigatran, is this safe to continue through their cataract surgery?”

What would you do if the patient were on warfarin?

What would you do in the case of dabigatran?

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Bridging for Minor Procedures

Procedure Bridging Recommendation

Cataract surgery Continue warfarin at normal dose (Grade 2C)• Clinically important bleeding <3%

Douketis et al. Perioperative Management of antithrombotic therapy. Chest [Internet]. 2012 Feb [cited 2015 April 21]. 141(2 Suppl):e326S-50S. doi: 10.1378/chest.11-2298

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New Oral Anticoagulants Dabigatra

n etexilate

Rivaroxaban Apixaban Edoxaban

Plasma peak (hours)

1.5–3.0 2.0–4.0 3.0-4.0 1.0-2.0

Elimination half-life (hours)

11–14: healthy

volunteers18–24:

significantly impaired

renal function

5–9: healthy volunteers

11–13: elderly

8–15: healthy volunteers

10 to 14 hours

Protein binding (%)

35% >90% 87% 55%

Elimination (%)

80% active renal

20% faecal

33% non-active renal

66% metabolized: (metabolism: 50%

renal and other half by

hepatobiliary route)

Multiples pathways:25%–29%

renal56% by faecal

route

50% renal excretion, 50%

via biliary/intestinal

excretion or minimally

metabolizedDincq, Anne-Sophie et al. Management of Non-Vitamin K Antagonist Oral Anticoagulants in the Perioperative Setting. BioMed Research International [Internet]. 2014 May 30[cited 2015 April 22]. Vol 2014, Article ID 385014

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Antidotes

Aripazine (PER977, ciraparantag) Synthetic D-arginine compound that will work against

heparin, LMWH and new oral anticoagulants Andexanet (PRT064445)

Recombinant, modified factor Xa molecule that will work against rivaroxaban, apixaban and edoxaban

Phase II and III trials ongoing. Idarucizumab (BI 655075)

Humanized Ab fragment directed against dabigatran Phase III study ongoing. Three Phase I trials have

been completed.

Taylor, VE. What is new in the anticoagulant antidote market? December 26, 2014. http://formularyjournal.modernmedicine.com/formulary-journal/news/what-new-anticoagulant-antidote-market?page=full

http://formularyjournal.modernmedicine.com/formulary-journal/news/what-new-anticoagulant-antidote-market?page=full






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WHEN TO BRIDGE

Moderate Risk Bleeding Procedures

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Scenario 3

Patient 1 Patient 2 Patient 355 y/o female with a CHADS2 score of 3 (afib, stroke) and a history of recurrent VTE. She is currently on warfarin and her last INR 2.3.

67 y/o male with a bileaflet mechanical aortic valve replacement. He does not have a history of VTE or atrial fibrillation. He is currently on warfarin and his last INR 2.8.

45 y/o female undergoing treatment for Stage II breast cancer. Her most recent VTE was 4 months ago and within the past 12 months she has had 2 VTEs. She is currently on LMWH.

The following patients will undergo moderate bleeding risk procedures. Which of the follow patient(s) needs to be bridged?

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2014 AHA/ACC Valvular Heart Disease Guidelines on Bridging for Prosthetic Valves

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2014 AHA/ACC Valvular Heart Disease Guidelines on Bridging for Prosthetic Valves

Stop VKA 2 to 4 days before the procedure (so INR falls to <1.5 for major surgical procedures). (Grade 1C)

CHEST Guidelines 2012 recommends stopping VKA 5 days before procedure (Grade 1B).

IV unfractionated heparin or subQ LMWH is started when INR <2.0 and stopped 4-6 hours (for IV UFH) or 12 hours (subQ LMWH) before procedure. Use therapeutic weight-adjusted LMWH dosing.

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WHEN TO BRIDGE

High Risk Bleeding Procedures

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Cardiovascular Surgeries Noncardiovascular Surgeries

Cardiac surgery (CABG, PCI, heart transplant, heart valve replacement, carotid endareterectomy, etc.)

Pacemaker or implantable cardioverter-defibrillator device (ICD) implantation*

Urologic surgery and procedures Intracranial or spinal surgery Colonic polyp resection Surgery in highly vascular organs

(kidney, liver, spleen) Bowel resection Major surgery with extensive tissue

injury (cancer surgery, joint arthroplasty, reconstructive plastic surgery)

Laminectomy Thyroid surgery

High Bleeding Risk Procedures—Bridging Not Recommended

Douketis et al. Perioperative Management of antithrombotic therapy. Chest [Internet]. 2012 Feb [cited 2014 Oct 22]. 141(2 Suppl):e326S-50S. Doi: 10.1378/chest.11-2298

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Bridging for Cardiac Device Placement

Pacemaker or ICD placement RCT Trial Moderate to high risk patients

338 patients assigned heparin bridging (326 underwent surgery)

343 assigned to continued warfarin (335 underwent surgery)

Clinically significant hematoma Heparin bridging: 54 (16%) Warfarin continuation: 12 (3.5) Relative risk: 0.19 (95% CI: 0.10-0.36)

Guidelines recommend bridging for pacemaker or ICD placement for high risk patients but studies show this may not be necessary because the risk of bleeding may outweigh the risk of thromboembolism.

Birnie et al. Pacemaker or Defibrillator Surgery without Interruption of Anticoagulation. N Engl J Med [Internet]. 2013 May 30 [cited 2014 Oct 22]. 30;368(22):2084-93. doi: 10.1056/NEJMoa1302946.

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Anticoagulation for Cardioversion

Patients who will undergo cardioversion need to undergo full anticoagulation for ___ weeks before procedure and for ____ weeks after procedure. (Grade 1B)

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You JJ, Singe DE, Howard PA, et al. Antithrombotic therapy for Atrial Fibrillation. Chest [Internet]. 2012; 141(2_suppl):e531S-e575S. doi:10.1378/chest.11-2304

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SHOULD YOU BE BRIDGING?

Managing Subtherapeutic INRs

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CHEST 2012 Guidelines for Managing 1 Out-of-Range INR

For patients taking VKAs with previously stable therapeutic INRs who present with a single out-of-range INR of ≤ 0.5 below or above therapeutic, we suggest continuing the current dose and testing the INR within 1 to 2 weeks (Grade 2C).

For patients with stable therapeutic INRs presenting with a single subtherapeutic INR value, we suggest against routinely administering bridging with heparin (Grade 2C).

Holbrook A, Schulman S, Witt DM, et al. Evidence-Based Management of AnticoagulantTherapy. Chest. 2012;141(2_suppl):e152S-e184S. doi:10.1378/chest.11-2295.

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Is bridging necessary for 1 subtherapeutic INR?

Retrospective chart review in 710 patients found 546 episodes of isolated subtherapeutic INR in 320 patients at a pharmacist-managed ACC.

Subtherapeutic INR was preceded by 2 INRs within or above range.

18% of all subtherapeutic INR episodes (98 episodes) were bridged with parenteral agents (enoxaparin, fondaparinux).

Hwang JM, Taylor TN, Sharma KP, Clemente JL, Garwood CL. Bridging for an isolated subtherapeutic INR: an Evaluation of clinical practice patterns, outcomes and costs from an anticoagulation clinic. J Thromb Thrombolysis (2012). 33:28-37. DOI 10.1007/s11239-011-0643-0.

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Is bridging necessary for 1 subtherapeutic INR?


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IS Bridging necessary for 1 subtherapeutic INR?

Bridged vs Non-bridged Bruising (18.4% vs 3.6%) Minor bleed (4.1% vs 3.1%) Major bleed (2% vs 1.3%) Thrombosis (2% vs 0.7%)

2 in bridged episodes 3 in non-bridged episodes

Bridging is associated with more bruising and required more follow-up in clinic and placed a greater medical cost burden on the patient so the authors suggest that bridging is of little benefit to the patient.


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Questions

Documents

Warfarin Bridging