COMMENTARY

The Future for NOACs in Light of ENGAGE-AF

E Magnus Ohman, MD; Jessica L Mega, MD, MPH

Disclosures

December 10, 2013

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In This Article

E Magnus Ohman MD: Hello, I'm Magnus Ohman from Duke University Medical Center in North Carolina, and with me today is Dr Jessica Mega, who's assistant professor of medicine at Brigham and Women's in Boston. Jessica, we are here at the AHA Scientific Sessions, with yet another novel oral anticoagulant being presented with striking results. What did the ENGAGE-AF trial of edoxaban show?

ENGAGE-AF Findings

Jessica L Mega, MD: This was really exciting when we think about the series of trials that we've seen before. This was a trial of over 20 000 patients with atrial fibrillation.[1] These patients were being treated with warfarin, a low-dose strategy of edoxaban, or a high dose strategy of edoxaban. We should note that edoxaban is a factor Xa inhibitor. Overall, what was seen in this trial is that the edoxaban, the novel oral anticoagulant, met its noninferiority boundary, so what does that mean? It means it was at least as good as warfarin when we think about stroke or systemic embolic events. These drugs were safer in terms of major bleeding and ICH, and interestingly, both doses led to a mortality benefit when we think about cardiovascular mortality. When we think about the totality of the data, this is really exciting news here at the American Heart Association meeting.

Dr Ohman: Help me put this into context now. We have two oral Xa inhibitors and one direct thrombin inhibitor (all oral agents). How would you ever pick any one of these over our standard?

Lumper vs Splitter

Dr Mega: It makes me think about the way you think. Are you a lumper or are you a splitter? If you're a lumper, what you would say is this is really great news because if you look at dabigatran, you look at rivaroxaban, apixaban, and now edoxaban, all of these have very similar messages—at least as good as warfarin on the efficacy side, definitely safer, and this mortality benefit that we're seeing. Again, a lumper would say great news. We have a better way that we can treat atrial-fibrillation patients. If you're a splitter and you're trying to find some of the nuances, I think there are three key pieces. One is that the patient populations were slightly different, so the sickest patients were in the ROCKET-AF trial with rivaroxaban,[2] and then as you get to some of the other trials, patients with lower CHADS2 scores. So that's one thing, maybe the patient population. What about the drug itself? Dabigatran and apixaban are twice a day, whereas edoxaban and rivaroxaban are once a day, and then finally there's varying degrees of creatinine-clearance impact on the drug, but again I tend to be a lumper, and I see these as really supporting the same biologic hypothesis.

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