Experience | Approximately 60 y |
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Efficacy |
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Apixaban and 150 mg of dabigatran twice daily had less stroke and systemic embolism versus warfarin. NNT ranged from 88–167 over approximately 2 y. Lower mortality rates with apixaban; NNT was 132 over approximately 2 y -
Rivaroxaban and 110 mg of dabigatran twice daily were as effective as warfarin for the same end point
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Safety |
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Risk of nonhemorrhagic stroke when INR < 2 -
Risk of bleed when INR > 3, particularly with an INR > 4.5
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Less intracranial bleed compared with warfarin -
NNT ranged from 96–250 over approximately 2 y -
Apixaban had least amount of bleeding -
Increased risk of GI bleed with dabigatran and rivaroxaban (NNH = 100/y for both drugs) -
Dabigatran also had more dyspepsia and an increasing trend toward MI
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Antidote |
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No established antidote or procedure for reversal -
Potential options with apixaban and rivaroxaban: prothrombin complex concentrate, recombinant factor VIIa, activated charcoal if < 2–3 h of administration -
Potential options with dabigatran: dialysis, activated charcoal if ≤ 2 h of administration
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Monitoring |
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Routine and frequent INR tests -
Frequency can be extended to every 1–3 mo once dose stabilized -
Can provide reassurance of drug efficacy and safety (ie, within target range)22
| SCr and calculated CrCl—at least annually |
Pharmacokinetics |
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Drug interactions |
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Fewer drug interactions but lacking experience to determine clinical significance of these -
Strong inhibitors of both CYP 3A4 and P-glycoprotein are contraindicated with all 3 new agents (eg, azoles, ritonavir) -
Caution with CYP 3A4 and P-glycoprotein inducers (eg, rifampin, phenytoin carbamazepine, St John’s wort) and inhibitors (eg, verapamil, amiodarone, dronedarone, quinidine)
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Dosage |
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Renal impairment (CrCl < 30 mL/min) | No dose adjustment required |
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Reduce dose -
Patients with renal impairment were excluded from trials -
Apixaban: excluded patients with CrCl < 25 mL/min. Reduce dose to 2.5 mg twice daily in patients with 2 of the following: age ≥ 80 y, body weight ≤ 60 kg, and SCr ≥ 133 μmol/L (CrCl < 25 mL/min) -
Dabigatran: excluded patients with CrCl < 30 mL/min. This degree of renal impairment is considered a contraindication in Canada. Consider 110 mg twice daily in patients with CrCl 30–50 mL/min -
Rivaroxaban: excluded patients with CrCl <30 mL/min. Reduce dose to 15 mg/d if CrCl 30–49 mL/min
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Cost/mo |
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Other | Anticoagulant-management clinics might be available and increase
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Apixaban: not approved by Health Canada for stroke prevention -
Dabigatran: capsules; packaged in blister packs or bottles; must be stored in original container (ie, cannot be pill or compliance packaged); capsules from bottles must be used within 4 mo of opening
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