Table of contents
- 1. Bottom Line
- 2. Oral Anticoagulants
- 3. Trials
.
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) Dabigatran 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) Apixaban Less stroke and less major bleeding
(superior to warfarin)
Edoxaban - When to use:
-
Drug When to use Warfarin - Mechanical heart valves or valvular AF
- Hepatic dysfunction (esp if baseline INR elevated)
- Renal dysfunction (CrCl < 30)
Dabigatran - DO NOT use if dyspesia (or gi complaints), dabi worsens by 10%
- Low risk of stroke
Rivaroxaban - Poorly compliant with BID drugs (prefers OD)
- CrCl 30-50 ml/Min
- High risk of stroke (higher risk pts in ROCKET-AF)
Apixaban - 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) | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Dabigatran Trade Name: Pradaxa | Direct Thrombin Inhibitor
Excretion: Hepatic Metab. Urine (80%) Half-life: 12-17h
| Warning: doses for general knowledge only (check manufacturer labeling)
CrCl 30-49 = use 110mg (caution CrCl < 30 = do not use |
| ||||||||||
Rivaroxaban Trade name: Xarelto Canada: Bayer Pharm. | Factor Xa Inhibitor
Excretion: 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 |
| ||||||||||
Apixaban Trade Name: Eliquis by Pfizer and Bristol-Myers Squibb | Direct Factor Xa Inhibitor
Excretion: 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 |
|
Trials
- 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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