Tools for Practice

#73 Novel Oral Anti-coagulants (NOACs): is newer better?

For patients with non-valvular atrial fibrillation (AF), do the NOACs (dabigatran, rivaroxaban, apixaban) have advantages over warfarin?

Compared to warfarin, NOACs offer some benefits for patients with non-valvular atrial fibrillation. The decision to use a NOAC or warfarin should be made after reviewing the patient’s previous INR stability, kidney function and discussing the potential benefits and risks, direct and indirect costs with the patient.

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All randomized controlled trials compared NOACs to warfarin: patients mean age 70-73 years, 35-40% female, 1.8-2 years follow-up. All outcomes versus warfarin:
  • Dabigatran: 150mg BID or 110mg BID,1,2 18, 113 patients, mean CHADS2=2.1.
    • Stroke & systemic embolism:
      • 150mg: 0.60% less/year, Number Needed to Treat (NNT)=167.
      • 110 mg: No statistical difference.
    • Major Bleed:
      • 150mg: No statistical difference.
      • 110mg: 0.70% less/year, NNT=143.
    • o Mortality:
      • 150mg: Borderline significance [p=0.051, absolute difference would be 0.49% less/year, NNT=205].
      • 110mg: No statistical difference.
  • • Rivaroxaban: 20mg QD,3 14,264 patients, mean CHADS2=3.5.
    • Stroke & systemic embolism, major bleed, or mortality: No statistical difference.
  • • Apixaban: 5mg BID,4 18,201 patients, mean CHADS2=2.1
    • Stroke & systemic embolism: 0.33% less/year, NNT=303.
    • Major Bleed: 0.96% less/year, NNT=104.
    • Mortality: 0.42% less/year, NNT=238.
**Dose of rivaroxaban3 and apixaban4 adjusted for renal impairment,3,4 age,4 weight.4 Context:
  • While statistical significance was achieved in some endpoints, whether clinically meaningful differences exist between the agents is unknown.
  • In Canada, only dabigatran and rivaroxaban are currently approved for AF stroke prevention.
  • Appropriate patient selection important:
    • Use CHADS2, time in therapeutic INR range, and tools to aid discussion.
    • NOACs contra-indicated in patients with significant renal impairment (CrCl < 30 mL/min), use lower doses if moderate renal impairment (CrCl 30-50 mL/min).5
  • Major bleeding occurs with all anticoagulants:
    • NOACs: no established reversal strategy.
    • Bleeding risk factors: (primarily from dabigatran experience): age > 80 years, impaired6 or deteriorating renal function5, < 60 kg6, and starting before INR < 2.0.6
  • Potential risk of myocardial infarction (dabigatran): Number Needed to Harm (NNH)=250-500.1,2,7

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  • Michael R Kolber MD CCFP MSc
  • Tammy Bungard BSP PharmD

1. Connelly S, Ezekowitz MD, Yusuf S, et al. N Engl J Med. 2009; 361:1139-51.

2. Connelly S, Ezekowitz MD, Yusuf S, et al. N Engl J Med. 2010; 363:1875-6.

3. Patel MR, Mahaffey KW, Garg J, et al. N Engl J Med. 2011; 365:883-91.

4. Granger CB, Alexander JH, McMurray JJV, et al. N Engl J Med. 2011; 365:981-92.

5. Health Canada Endorsed Important Safety Information on Pradax (dabigatran etexilate) March 16, 2012. Available at: dhcpl.pdf. Last accessed Dec 12, 2016.

6. Harper P, Young L, Merriman E. N Engl J Med. 2012; 366:864-6.

7. Uchino K, Hernandez AV. Arch Intern Med. 2012; 172:397-402.

Authors do not have any conflicts of interest to declare.