Table of contents




    Bottom Line

    Source: Weitz, JL and Gross PL. New oral anticoagulants: Which one should my patient use? Hematology 2012

    • Class Effect
      • ALL are non-inferior to warfarin for prevention of stroke (ischemic and hemorrhagic) or embolism
      • ALL have less intracranial bleeds than warfarin 
      • ALL have rates of major bleeding similar or lower than warfarin
      • ALL have approx. 10% reduction in mortality comp. to warfarin
      • No evidence of hepatic toxicity
    • Differentiating effects
      • Drug Benefits (comp. w/ warfarin) Drawbacks (comp. w/ warfarin)

        Less hemorrhagic and ischemic 

          stroke (superior to warfarin)

        Higher rate of MI

        Less effective than warfarin at preventing MI

        More GI bleeds (esp 150mg BID dose) than warfarin
          (esp in elderly)

        Most renal excretion (comp with riva and apix)

        Dyspepsia (or other gi complaints) in 10%

        Rivaroxaban   More GI bleeds than warfarin (esp in elderly)

        Less stroke and less major bleeding

          (superior to warfarin)

      • When to use:
      • Drug When to use

        - Mechanical heart valves or valvular AF

        - Hepatic dysfunction (esp if baseline INR elevated)

        - Renal dysfunction (CrCl < 30)


        - DO NOT use if dyspesia (or gi complaints), dabi worsens by 10%

        - Low risk of stroke


        - Poorly compliant with BID drugs (prefers OD)

        - CrCl 30-50 ml/Min

        - High risk of stroke (higher risk pts in ROCKET-AF)


        - CrCl 30-50 ml/min

        - If GI bleeding is an issue (riva and dabi150 worsen GI bleeds)

        - Low risk of stroke

        Edoxaban Not yet approved (2016)

    Oral Anticoagulants

    Drug Class Contraindications Indications (red) & Trials (blue)


    Trade Name:







    Hepatic Metab.

    Urine (80%)

    Half-life: 12-17h


    Warning: doses for 

    general knowledge only

    (check manufacturer labeling)



    CrCl 30-49 = use 110mg


    CrCl < 30 = do not use

    Non-Valvular AFib

    150mg BID

    110mg BID if high risk of bleed

    (≥1 risk factor, ≥70yo, but less efficacy)

    RE-LY Trial (2009)

    110mg dabi equals warfarin 

       for storke (but less bleeding)

    150mg dabi better than warfarin

       for stroke, but same 

       risk of major bleeds)

    RELY-ABLE Trial (2013)

    Long-term observational study

    150 and 110mg equal stroke 

    efficacy, but 150 = more bleeds

    DVT and PE Treatment & Prevention

    5-10d of UFH or LMWH then 

    150mg dabigatran BID

    (110mg if  high risk of bleed

    ≥1 risk factor, ≥70yo)


    RE-COVER 2

    both trials show dabigatran

    non-inferior to warfarin, and less

    bleeding risk


    Trade name: 



           Bayer Pharm.

    Factor Xa 




    Liver: 66%

    Unchanged: 33%

    Half-life: 5-9h


    (Check manufacturer labeling)

    CrCl ≥ 50 = OK

    CrCl 30-49 = 15mg OD

    CrCl < 30 = do not use


    Hepatic Impairment:

    Poor data

    Non-Valvular AFib

    (20mg OD with meals)

    ROCKET-AF Trial (2011)

    Non-inferior to warfarin for non-

    valvular AFib for stroke prevention

    Equal # of minor/major bleeds

    Less fatal bleeds & ICH than warfarin

    DVT Prophylaxis RECORD Trial?

    PE Treatment

    15mg BID x3w then 20mg OD x3/6/12mo)


    Non-inferior to "standard therapy" 

    (enox & warfarin) and less bleeding 

    DVT Treatment &

    Recurrence Proph

    (15mg BID x3w then 20mg OD x3mo)


    Rivaroxaban non-inferior to vitamin

    K antagonists and enox (less bleeds?)

    Post-op DVT prophylaxis

    Hip: 10mg OD x12-14d (up to 35d)

    Knee: 10mg OD  x10-14d (up to 35d)

    RECORD Trial

    (more effective than enox, equal




    Trade Name:


    by Pfizer and




    Factor Xa 




    Biliary (75%)

    Renal (25%)

    Half-life: 9-14h

    (Check manufacturer labeling)


    CrCl < 15 = do not use


    Use 2.5mg BID if: 

    (reduced dose)

    - Age ≥ 80

    - Weight ≤ 60kg

    - Creat > 133 umol/L


    Hepatic Impairment:

    Do not use in Child's 

    Pugh Class C 

    Non-Valvular AFib

    5mg BID

    2.5mg BID (for some pts)

    ARISTOTLE Trial (2011)

    SUPERIOR to warfarin in stroke/embolism

    Less fatal bleeds, LOWER mortality

    PE/DVT Treatment

    10mg BID x7d

    then 5mg BID...

    AMPLIFY Trial (2013)

    Non-inferior to "standard treatment"

    Less bleeding risk

    DVT Recurrence Proph

    2.5mg BID (after 6mo of 

    VTE treatment) [2014]

    AMPLIFY-EXT Trial (2013)

    Effective 5mg and 2.5mg

    Post-OP DVT Proph

    Hip: 2.5mg BID x35d

    Knee: 2.5mg BID x12d

    ADVANCE-1 Trial (knees)

    Did not prove non-inferiority over enox, 

    less bleeding.

    ADVANCE-2 Trial (knees)

    More effective than enox, less bleeding

    ADVANCE-3 Trial (hips)



    • ROCKET- AF Trial
      • Rivaroxaban 20mg daily vs. warfarin in 14,264 non-valvular AF pts
      • Per protocol and intention-to-treat
      • Hazard Ratio 0.79 (P= < 0.001 for non-inferiority)   
        • Non-inferior in ITT && PP analysis
      • Rivaroxaban = same # bleeding events as warfarin
      • Rivaroxaban = less fatal bleeding (0.2 vs. 0.5%) + less ICH (0.5 vs. 0.7%)
      • Drawbacks: INR therapeutic in only 55% of warfarin group
        • NOT superior to warfarin in ITT analysis
    • ARISTOTLE Trial
      • Apixaban 5mg daily vs. warfarin in 18,021pts with non-valvular AF
      • Primary Outcome: (ICH/stroke/systemic embolism)
        • 1.27%/yr vs. 1.60%/yr (HR: 0.79%, p=<0.001)
      • Apixaban = less major bleeds 2.13 vs. 3.09%/yr (p=<0.001)
      • Apixaban = less 3.52  vs. 3.94% (p=0.047)
      • Apixaban = less hemorrhagic stroke 0.24%/yr vs. 0.47%/yr (p=<0.001)
      • Drawbacks: Therapeutic INR reached  62% of time in warfarin group
    • RE-LY Trial
      • Dabigatran 110mg vs. Dabigatran 150mg vs. Warfarin (unblinded warfarin) in 18,113 pts
      • Primary Outcome: (Stroke/Systemic Embolism)
        • 1.53%/yr 110mg dabigatran BID vs.
        • 1.11%/yr 150mg dabigatran IBD vs.
        • 1.69%/yr warfarin (P=<0.001 for non-inferiority)
      • Dabigatran = Less major bleeding 2.71%/yr (110 dabi) vs. 3.11%/yr (150 dabi) vs. 3.36%/yr (warfarin) p=0.003
      • Dabigatran = Less hemorrhagic stroke: 0.12%/yr (110 dabi) vs. 0.10%/yr (150 dabi) vs.0.38%/yr (warfarin)p<0.001
      • Dabigatran = Less mortality: 3.75% (110 dabi) vs.  3.64% (150 dabi) vs. 4.13%/yr (warfarin) p<0.051
      • Drabacks: 
    • AVERROES Trial
      • Compared to ASA, apixaban has slightly increased risk of bleeding, but difference was non-significant.
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