Warfarin

Monitoring

• INR

  • documented in clincial notes

    • on warfarin

    • condition for which warfarin has been prescribed

    • target INR range

    • planned duration of treatmnet

    • brand of warfarin

Managing warfarin treatment

• risk of bleeding greatest who have not received warfarin and in first 3 months

• Any patient on warfarin should be aware of risks and early warning signs of bleeding

  • followed closely to ensure INR not >3

• for most people testing every 2,4,6,8 weekly depending

• target = 2.5 for most (2-3)

  • prophlaxis/treatment VTE

  • AF

  • valvular heart disease

  • (mechanical valve dependent of type of valve)

• duration = 13 wks for provoked DVT or PE

• unprovoked = 13wk but indefinite use may be appropriate

• AF, cardiomyopathy, valvular heard disease = indefinite

• changes in INR

  • major changes in diet or etoh

    • consistent proportion of vit K rich food(brocooli, spinach, cabbage)

  • drug interactoins

    • plus interactions that don’t change INR and increase risk of bleeding; NSAIDS, aspriin, ssri

  • systemic or concurrent illness

    • CHF

      • hepatic congestion

    • hypothyroidism

      • decrease catabolism of vit K clotting factors

    • hyperthyroidism

      • increase catabolism of vit k clotting factors

    • liver failure

  • non-adherence to dosage regime

    • change in INR 2-5d after missed dose

  • unknown

• computerised decision support > human

  • better control

  • fewer tests

• stop antiplatelets if starting warfarin for anything other than complicated ACSwhere clopidogrel/aspriin short term may be useful in those with low bleeding risk

Drug interactions

Inhibit: increase risk of bleeding

• Antibiotics

  • most

  • macrolides

  • metronidazole

  • quinolones

  • cotrimoxazole

• antifungazole

  • fluconazole, miconazole

    • including gel and vaginal preparations

• SSRI

  • inhibit with platelet function

    • increase risk without change INR

  • fluoxetine also inhibit warfarin metabolism

• Antiplatelet

  • aspirin, clopidogrel, dipyridamole

    • interfere priamry haemostasis

• Amiodarone

• NSAIDS

  • direct mucozal injury

• Paracetamol

  • direct interference with Vit K cycle

  • unlikely with short term use

Induction - increased thromboisis

• rifampicin

• St John’s wort

• foods with high vit K content

bleeding risk

• concomitant use of aspirin

• polypharmacy - 7 or more medications

• other comorbidities

• rate of spontaneous intracranial haemorrhage >70yo = 0.15%

• BAFTA = significantly lower risk of stroke, intracranial haemorrhage or arterial embolism but same risk of bleeding as aspirin

• HAS BLED = ≥ 3 = high risk of bleeding

  • Hypertension (sbP >160)

  • abnormal renal and liver function (1each)

  • stroke (1)

  • bleeding

  • labile INR

  • elderly >65

  • Drugs or etoh (1 each)

  • max = 9

over anti-coagulation:

• INR 5-9

  • stop warfarin

  • test daily until therapeutic

  • restart wiht reduced dose when INR \<5

  • Give vit K 1-2.5mg orally if INR fails to reduce or if high risk of serious bleeding

• INR >9 without bleeding

  • stop

  • vit K 2.5-5mg orally

  • measure in 24hrs

  • restart at reduced dose when INR \<5

• INR ≥ 9 with minor bleeding

  • stop

  • vit k 1-5mg

  • test daily

  • restart warfarin

• major bleeding

  • stop

  • vit k 10mg slow IV

  • refer for factor replacement

Dabigatran

Indications

• prevention of stroke in non-valvular atrial fibrillation

  • requires at least one other risk factor

    • previous TIA/Stroke

    • LVEF \< 40%

    • symptomatic heart failure

    • age ≥ 75uo

    • age ≥ 65 + DM or HTN or CAD

  • NOT indicated valvular heart disease or mechanical heart valves

  • NOT been evaluated with bioprosthetic valves

• VTE prophlaxis after major orthopaedic surgery

• (treatment of VTE)

• contraindicated with ketoconazole

Dosing

• 150mg bd provided CrCl >30mL/min

• 110mg bd aged ≥ 80yo

• aged 75-80 with CrCl 30-50 consider 110mg bd: if risk of bleeding high and risk of thrombosis low

• for VTE prophlaxis

  • 220mg OD CrCl >50

  • 150mg OD Cr 30-50

advantages over warfarin

• more convient

• effective anti-coagulation in those who previously difficult to ontrol on warfarin

  • assuming adherence good

• fewer drug and dietary interactions than warfarin

• reduction in risk of intracranial haemorrhage

initiating

• all patients should have assessment of renal function

  • CI in CrCl\<30

• if already anti-coagulated

  • warfarin stopped

  • started when INR \<2

• Change back - warfarin

  • check CrCl

    • if >50mL/min warfarin started 3 days prior before discontinuing dabigatran

    • if 30-50mL intiiate warfarin 2 days before stopping dabigatran

• stopping prior to planned surgical procedure

  • CrCl >50

    • 24hours prior

    • or 48hrs if high risk of bleeding/major

  • 30-50

    • 2-4 days - action prolonged

Monitoring

• renal function

  • initiation

  • change in clincial situation

  • annually >75

  • annually (but pref 3-6mo) cr cl 30-50

• wide therapeutic window, predictable pharmacokinetics and pharmacodynamic

• rapid onset of action

• if bleeding

  • stop

    • Thrombin time

    • activated partial thromboplastin time

    • fibrinogen

    • ecarin clotting time

Adverse effects

• non-haemorrhagic GI adverse effects = most frequent

  • dyspepsia

    • treat with PPI

      • not significant interaction

• bleeding

  • can be minimised

    • correct dose

    • inr \<2 on initiation

    • used in caution with other medicines that increase bleeding