New Oral Anticoagulants GuidelinesKAI YAP

What’s wrong with traditional anticoagulants???

Development

Traditional anticoagulants have 2 major limitations:

- Narrow therapeutic window of adequate anticoagulation without bleeding

- Highly variable dose-response, requiring monitoring by lab testing

These limitations have provided impetus for development of other antithrombotic agents.

3 new oral anticoagulants (NOAC) dagibatran, rivaroxaban, apixaban listed on PBS.

MechanismDagibatran – direct thrombin inhibitorRivaroxaban – factor Xa inhibitorApixaban – factor Xa inhibitor

Indications

1. Prevention of venous thromboembolism in a patient undergoing total hip or knee replacement

2. Prevention of stroke or systemic embolism in patients who have non-valvular atrial fibrillation and has one or more risk factors for developing stroke or systemic embolism

3. Rivaroxaban for the prevention of recurrent venous thromboembolism and for the treatment of deep vein thrombosis and pulmonary embolism.

Contraindications

Known hypersensitivity to ingredients of NOAC

Clinically significant active bleeding

Renal impairment <30ml/min

Hepatic disease (child pugh – C)

Recent high risk bleeding lesion (eg. ICH < 6 months)

Pregnancy or breast feeding

Recent stroke, surgery, GI bleed or ulcer

Recent fibronolytic therapy <10days

Concomitant warfarin therapy

Features of NOAC

Features to consider

- Faster onset

- Shorter ½ life

- Less drug-drug interactions

- No need for monitoring with NOACs

- No antidotes

Dosing – Total hip / knee replacement (VTE prophylaxis)

Dagibatran Rivaroxaban Apixaban

Crcl > 50ml / min 220mg once daily 10mg once daily

Crcl 30–50ml / min 150mg once daily 10mg once daily 2.5mg once daily

Crcl 15-30ml / min contraindicated contraindicated

Dosing – Non-valvular Atrial Fibrillation

Dagibatran Rivaroxaban Apixaban

Crcl > 50ml / min 150mg twice daily

20mg once daily

Crcl 30-50ml / min

110mg twice daily

15mg once daily 5mg twice daily

Crcl 15-30ml / min

Contraindicated Contraindicated

Special populations

Older than 75 years old110mg twice daily

Not applicable At least two of following:-older than 80 yo-Weight less than 60kg-Scr > 133micromol/L

-2.5mg twice daily

Dosing – treatment of DVT / PE

Rivaroxaban

Crcl > 30ml / min

15mg twice daily for three weeks, followed by 20mg daily

Switching anticoagulants

Switching from Switching to Instructions

LMW Heparin NOACs When next dose of LMW Heparin is due

Heparin NOACs Immediately when heparin ceased

Warfarin NOACs Start once INR < 2

Dagibatran LMW heparin / UFH No bolus required. Start 12 hrs after last dose

Rivaroxaban / Apixaban LMW heparin / UFH No bolus required. Start 24 hrs after last dose

NOACs Warfarin Continue NOAC and give warfarin ≤ 5 mg Stop NOAC once INR ≥ 2 on 2 consecutive days

What do we do when patients bleed?

Management of bleeding (Initial Ix)

Seek early haematology advice

Dagibatran:

Measure: FBC, U&E, LFT, coagulation profile, Haemoclot and dabigatran level

normal TT excludes dabigatran activity

normal aPTT suggests bleeding not due to dabigatran

Management of bleeding (Initial Ix)

Rivaroxaban / Apixaban:

Measure: FBC, U&E, LFT, coagulation profile, anti-Xa and rivaroxaban level

normal PT suggests rivaroxaban level not high

aPTT cannot predict anticoagulant effect

tests are currently inconclusive for apixaban

Management of bleeding (mild)

Mild bleeding -

- local haemostatic measures

- delay or discontinue NOAC as required

Management of bleeding (clinically significant)

reduction in Hb >20 g/L or requiring RBC transfusion > 2 units

Stop NOAC therapy

Give oral charcoal if NOAC ingested < 2 hours ago

Maintain adequate hydration to aid drug clearance

Local haemostatic measures: mechanical compression

Transfusion support: RBC transfusion as per Hb level

Consider platelet transfusion if on antiplatelet therapy or if platelets < 50 x 109/L

Consider radiological and surgical interventions to identify and treat source of bleeding

Management of life threatening bleeding

bleeding in critical area or organ, loss of Hb > 50 g/L, hypotension not responding to resuscitation

Get advice of haematologist!!! T/f to SCGH or RPH

a)FEIBA (factor eight inhibitor bypass activity) 25 -100 International Units/kg, repeat at 12 hours (probably beneficial)

b)rVIIa 90 microgram/kg every 2-3 hours (possibly beneficial) c)prothrombinex – VF 25-50 International Units/kg (if not

administered earlier) d)tranexamic acid 15-30 mg/kg IV for mucosal bleeds

Prescribing a new oral anticoagulant

1. Lab tests – FBC, EUC, LFTs

Contraindications:

-Poor renal function (CrCl ≤ 30 mL/ min, apixaban: ≤ 15 mL/min)

-Liver disease (e.g. ALT > 3x upper limit of normal)

-Hb ≤ 100 g/L (assess risk vs. benefit)

Prescribing a new oral anticoagulant

2. Detailed History

EXCLUSION Criteria:

-Known hypersensitivity to NOAC preparation

-Pregnant or breastfeeding

-Stable warfarin therapy

-Prosthetic heart valve

-Recent stroke

Prescribing a new oral anticoagulant

3. Assess bleeding risk

-Disorder of haemostasis

-Recent surgery (≤ 1 month ago)

-GI bleed ≤ 12 months ago

-Ulcer ≤ 30 days ago

-Fibrinolytic treatment last 10 days

-Dual antiplatelet therapy

Prescribing a new oral anticoagulant

4. Consider contaminant medications

Rivaroxaban / apixaban

-Systemic azole antifungals (except fluconazole)

-HIV-protease inhibitors

Dabigatran

-Systemic azole antifungals (except fluconazole)

-dronedarone

-Simultaneous initiation with verapamil

-cyclosporin and tacrolimus

Prescribing a new oral anticoagulant

Is patient on warfarin?

Stop warfarin

Start NOAC once INR < 2

Western Australia Therapeutic Advisory Group Guidelines

Please visit http://www.watag.org.au/watag/publications.cfm#guidelines