Efficacy and safety of edoxaban in comparison with dabigatran, rivaroxaban and apixaban for stroke prevention in atrial fibrillation: An indirect comparison analysis

How to choose a Novel Oral Anticoagulant (NOAC) for stroke prevention in atrial fibrillation: fitting the drug to the patient (and vice versa)

Non-Vitamin K Oral Anticoagulants (NOACs, previously called new or novel oral anticoagulants) are now alternatives to the traditional vitamin-K antagonists (VKAs, eg warfarin)  for stroke prevention in patients with atrial fibrillation. However, head-to head trials of the various NOACs are lacking. Thus, all available comparisons are indirectly based on the result of the phase-III studies comparing each NOAC with warfarin.

Previously, the only available oral anticoagulants were vitamin-K antagonists. Today, with the availability of four NOACs (dabigatran, rivaroxaban, apixaban and – most recently – edoxaban) clinicians have a choice and can match the drug to the patient, and vice versa. Moreover, individual preferences of the patient may be incorporated into the final decision about any future treatment.

Following the recent publication of the ENGAGE-AF trial with the Factor Xa inhibitor, edoxaban - biostatistician Flemming Skjøth, MSc, PhD, Aalborg University Hospital, Thrombosis Center, Aalborg, Denmark, and his team performed the first indirect comparison of safety and efficacy of edoxaban against the other NOACs, i.e. dabigatran, rivaroxaban and apixaban.

This recent analysis, published in the May 2014 issue of "Thrombosis and Haemostasis" found some differences among the drugs they analyzed, allowing treatment choices according to the clinical profile of each patient. Indirect comparisons of efficacy endpoints demonstrated that high-dose edoxaban was comparable to dabigatran 110 mg bid, yet inferior to dabigatran 150 mg. Moreover, high-dose edoxaban was comparable in efficacy to apixaban, but apixaban had less bleeding endpoints.

Efficacy of low-dose edoxaban was either similar or less effective than its competitors. When safety endpoints were compared, low-dose edoxaban emerged as the best, with the least bleeding  The differences among the drugs also suggested that patient-related factors such as expected compliance, individual focus on efficacy and side-effects as well as renal function, shall be taken into account when selecting a drug.


By providing the current analysis, the authors have presented for the first time, comparisons of efficacy and safety of edoxaban with other NOACs. Still, the authors emphasized that their findings, similarly to previous indirect comparisons of NOACs, are not based on direct head-to-head comparisons (which remain the gold standaed), a reminder that the data should thus be considered with some caveats.

Skjøth F, Larsen TB, Hvilsted LR, et al. Opens external link in new windowEfficacy and safety of edoxaban in comparison with dabigatran, rivaroxaban and apixaban for stroke prevention in atrial fibrillation: An indirect comparison analysis.  Thromb Haemost 2014; 111: 981-988.

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