Apixaban Scores on Efficacy and Safety Over Warfarin in AF

The ARISTOTLE results hit the trifecta, winning on efficacy, safety, and mortality.

The results achieved what everyone has been striving for: to reduce strokes, bleeding, and mortality in atrial fibrillation (AF) patients, compared with the standard drug for stroke protection, warfarin. There are now two large, randomized, controlled trials that show the benefit of apixaban versus warfarin, both ARISTOTLE and AVERROES, which compared apixaban and aspirin in AF patients who were ineligible for or who had failed warfarin treatment.

Do these data give apixaban an edge over the other two new oral anticoagulants, dabigatran and rivaroxaban? That is a question that many people will ask and debate. With the data available now, apixaban looks pretty good. Apixaban’s significant reduction of mortality in the ARISTOTLE results is a key end point. Physicians, patients, and third-party payers may prefer to go with the agent that was proven to reduce all-cause mortality. Neither dabigatran nor rivaroxaban produced a significant survival benefit in their respective pivotal trials, although dabigatran came very close at the 150 mg b.i.d. dosage. I think people will gravitate to the ARISTOTLE results because the study was large, was well conducted, and had a very vigorous design.

But other factors will also come into play. Rivaroxaban offers once-daily dosing. And there is the issue of cost, which has cropped up for dabigatran, the only one of the new alternatives to warfarin for patients with AF currently on the U.S. market. I have seen limited uptake of dabigatran since its Food and Drug Administration approval for AF patients last October because of its cost, and because of the relatively high rate of gastrointestinal adverse effects it can cause.

Physicians want their reliance on warfarin to fade away because of the drug’s many limitations. But it is also familiar and cheap, and in a good warfarin clinic and with good patient compliance it works pretty well and is difficult to beat. With warfarin monitoring you know your patient’s anticoagulant state. Warfarin clinics won’t be shutting down any time soon, but all three of the new anticoagulants – dabigatran, rivaroxaban, and apixaban – beat warfarin on the important end point of reducing intracranial bleeds.

If a patient is doing well on warfarin it’s attractive to not rock the boat and change things. But there seems to be a real benefit from apixaban that holds up among the various subgroups examined. If I thought a patient would be compliant and cost was not an issue then I would consider switching even patients who are well maintained on warfarin to apixaban because the data look so strong.

Dr. Deepak L. Bhatt is chief of cardiology at VA Boston Health System and is a cardiologist at Brigham and Women’s Hospital in Boston. He has received research grants from Bristol-Myers Squibb and several other drug and device companies, and has served on the steering committee for the APPRAISE-2 trial of apixaban and on the executive committee for the ATLAS-2 trial of rivaroxaban.