Warfarin and Novel Anti-Coagulants: Management Before and After the Cath Lab

Drew Baldwin, MDVirginia Mason

Seattle, WashingtonNCVH | May 28, 2015 | 2:30 pm

• I have no disclosures.

Stroke risk reduction in non-valvular

atrial fibrillation

Prevention of DVT after hip or

knee surgery

Risk reduction for recurrent

DVT

Treatment of DVT and PE

aspirin

warfarin (Coumadin)

FDA approved FDA approved FDA approved FDA approved

dabigatran(Pradaxa)

FDA approved FDA approved FDA approved

rivaroxaban(Xarelto)

FDA approved FDA approved FDA approved FDA approved

apixaban(Eliquis)

FDA approved FDA approved FDA approved FDA approved

edoxaban(Savaysa)

FDA approved FDA approved

betrixabanNot yet FDA

approvedNot yet FDA

approvedNot yet FDA

approvedNot yet FDA

approved

Warfarin

• Radial access; INR < 3.0

– Avoids enoxaparin bridging

• Femoral access; INR < 1.7

• Vitamin K for reversal in case of bleeding complications

NOACs in the cath lab

• Planned procedures for a patient on a NOAC

• Emergency procedures (STEMI) for a patient on a NOAC

• Antiplatelet and anticoagulant therapy for a patient with PCI and atrial fibrillation

How long should NOACs be held before cardiac procedures?

CrCl < 15 CrCl 15-29 CrCl 30-49 Cr 50-79 Cr ≥ 80

Direct Xa inhibitors for a procedure with low bleeding risk

N/a > 36 hrs > 24 hrs > 24 hrs > 24 hrs

Direct Xa inhibitors for a procedure with high bleeding risk

N/a > 48 hrs > 48 hrs > 48 hrs > 48 hrs

DTI (dabigatran) for a procedure with low bleeding risk

N/a N/a > 48 hrs > 36 hrs > 24 hrs

DTI (dabigatran) for a procedure with high bleeding risk

N/a N/a > 96 hrs > 72 hrs > 48 hrs

• Procedures with low bleeding risk: coronary angiogram, pacemaker/ICD implant, EP study, SVT ablation.

• Procedures with high bleeding risk: PCI, AF ablation, VT ablation, TAVR

Based on: Baker N and Jennings HS. Novel Anticoagulants: Management in the Periprocedural Setting and During Complications. SCAI website, March 25, 2015.

When should NOACs be restarted after cardiac procedures?

• Procedures with low bleeding risk: resume 12-24 hours after the procedure

• Procedures with high bleeding risk: resume 48-72 hours after the procedure

• Procedures with low bleeding risk: coronary angiogram, pacemaker/ICD implant, EP study, SVT ablation.

• Procedures with high bleeding risk: PCI, AF ablation, VT ablation, TAVR

Based on: Baker N and Jennings HS. Novel Anticoagulants: Management in the Periprocedural Setting and During Complications. SCAI website, March 25, 2015.

Measuring NOAC levels

• Rivaroxaban

– PT can provide a qualitative assessment

– Chromogenic anti-Xa level calibrated for rivaroxaban

• Trough levels 4-96 ng/mL

• Usual lower level of measurable is < 50 ng/mL

• Apixaban

– PT can provide a qualitative assessment

– Chromogenic anti-Xa level calibrated for apixaban

• Trough levels 41-230 ng/mL

• Usual lower level of measurable is < 20 ng/mL

• Dabigatran

– aPTT can provide a qualitative assessment

– Plasma dilute thrombin time (dTT, Hemoclot)

– dTT > 65 seconds indicates increased risk for bleeding

Gehrie E, Tormey C. Arch Pathol Lab Med 2015; 139: 687-692.

Managing non-life threatening bleeding complications

• Apply local hemostasis if possible• Provide hemodynamic support (IV fluids, packed RBCs,

vasopressors)• Assess compliance and timing of the last dose• Get early consultation with a hematologist or blood bank physician• Consider platelet transfusions for thrombocytopenia (platelet count

< 60,000)• Consider desmopressin for coagulopathy or thrombopathy• For dabigatran, maintain diuresis (unless hypotensive or volume

depleted)• For dabigatran, consider hemodialysis• Wait

Additional measures for life-threatening bleeding

DTI (dabigatran) Factor Xa inhibitors

Oral charcoal for recent doses May be effective

Hemodialysis Effective in CKD Not likely to be effective

Andexanet alfa FDA-approved for bleeding complications in patients taking rivaroxaban or apixaban

Off-label therapies:

Unactivated prothrombin complex concentrate (Kcentra, Profilnine)

No effect Highly effective in experimental models

Activated prothrombin complex concentrate (Feiba NF)

Effective in experimental models

Effective in experimental models

Recombinant factor VIIa Effective in experimental models

Effective in experimental models

Factor II, IX, X concentrates Effective in experimental models

Andexanet alfa

• Factor Xa decoy• Recombinant engineered form of factor Xa produced in

CHO cells• Serine alanine change eliminates catalytic activity,

prevents cleavage of prothrombin

• Complete correction of coagulation parameters within 2 minutes of bolus; effects last 1-2 hours

• Approved for reversal of rivaroxaban (ANNEXA-R study)• Approved for reversal of apixaban (ANNEXA-A study)• Undergoing evaluation for reversal of edoxaban, betrixaban

Reversal agents in development

• Idarucizamab (aDabi-Fab)

– Antibody fragment against dabigatran

• Aripazine (ciraparantag, PER977)

– Small molecule binds to heparin, LMWH, oral factor Xa inhibitors

Antiplatelet and anticoagulant therapy for the patient with atrial fibrillation who also has ACS or a PCI procedure

Dewilde WJM, et al. Lancet 2013;381:1107-1115.

WOEST trial bleeding events:• 19.4% in patients

taking clopidogrel+ OAC

• 44.4% in patients taking aspirin + clopidogrel + OAC

Antiplatelet and anticoagulant therapy for the patient with atrial fibrillation who also has ACS or a PCI procedure

• Rivaroxaban PIONEER

• Apixaban AUGUSTUS

• Edoxaban EVOLVE

• Dabigatran RE-DUAL

Antiplatelet and anticoagulant therapy for the patient with atrial fibrillation who also has ACS or a PCI procedure

• Triple therapy (aspirin 81 mg daily + clopidogrel 75 mg daily + anticoagulant) for 1-3 months, then stop aspirin

• Individualize according to risk for bleeding and stent thrombosis.

NOACs in the cath lab

• Planned procedures for a patient on a NOAC:– Hold NOAC according to institutional protocols and individual

patient situations

• Emergency procedures (STEMI) for a patient on a NOAC:– Use radial access– Notify hematology/blood bank and prepare to manage any

bleeding complications

• Antiplatelet and anticoagulant therapy for a patient with PCI and atrial fibrillation – Individualize according to patient’s risk for bleeding

complications and stent thrombosis

Analyzing Clinical Trial Findings of the Efficacy and Safety Profiles of Novel Anticoagulants for Stroke Prevention in Atrial Fibrillation

Drew Baldwin, MDVirginia Mason

Seattle, WashingtonNCVH | May 29, 2015 | 2:15 pm