Lack long-term safety and efficacy data

Landmark AF trials were approximately 1.5–2 y

Reduces the risk of stroke by 64%

Depends on time spent in therapeutic range

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

Risk of nonhemorrhagic stroke when INR < 2

Risk of bleed when INR > 3, particularly with an INR > 4.5

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

Vitamin K 1–10 mg

If no significant bleeding and INR >10:

• - hold warfarin and give vitamin K 2.5–5 mg orally, then

• - reduce weekly dose by 20% and resume once INR in therapeutic range

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

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

Longer half-life (2.5 d)

• - Benefit: therapeutic levels despite a few missed doses

Shorter half-life (8–17 h)

• - Benefit: shorter half-life allows drug to be cleared more quickly, but half-life extended with renal impairment

Concern in noncompliant patients

Numerous well-documented drug interactions

INR monitoring and dosage adjustments often required with concomitant acute and chronic therapy

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)

Once daily

Target INR 2–3

Might require more than 1 pill per d or alternating dosing schedule

Dose and frequency depends on the indication

Stroke-prevention regimens are as follows:

• - apixaban 5 mg twice daily

• - apixaban 2.5 mg twice daily in patients with ≥ 2 of the following criteria: age ≥ 80 y, body weight ≤ 60 kg, and SCr ≥ 133 μmol/L

• - dabigatran 150 mg twice daily

• - dabigatran 110 mg twice daily in patients who are ≥ 80 y or who are 75–79 y with ≥ 1 bleeding risk factor

• - rivaroxaban 20 mg once daily with food

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

Approximately $40 (includes INR monitoring cost)

Warfarin remains more cost effective than the new oral anticoagulant even after considering the cost of INR monitoring¹⁹

Apixaban $150–$290

Dabigatran $110

Rivaroxaban $100

Might not be covered by provincial or hospital formularies

monitoring efficiency and

time in therapeutic range

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