Choosing a DOAC? Apixaban May Have an Edge Over Rivaroxaban

In everyday practice, patients with atrial fibrillation or flutter who are newly started on apixaban (Eliquis; Bristol-Myers Squibb) have lower ischemic and bleeding risks compared with those started on rivaroxaban (Xarelto; Bayer/Janssen), a claims-based study shows.

Apixaban users had lower risks of ischemic stroke/systemic embolism (6.6 vs 8.0 per 1,000 person-years; HR 0.82; 95% CI 0.68-0.98) and GI bleeding/intracranial hemorrhage (12.9 vs 21.9 per 1,000 person-years; HR 0.58; 95% CI 0.52-0.66), according to researchers led by Michael Fralick, MD, PhD (Brigham and Women’s Hospital, Boston, MA).

An analysis restricted to patients older than 70 provided similar results, they report in a study published online March 9, 2020, ahead of print in the Annals of Internal Medicine.

“I had a gut feeling that apixaban might be safer and more effective, but I was pretty impressed to see that the rate of bleeding was much lower with apixaban compared to rivaroxaban,” Fralick told TCTMD. “So that was certainly both surprising and reassuring, and fits with some of the prior literature.”

It’s difficult to draw firm conclusions without a randomized comparison of the two drugs, Fralick said, but “I think that there’s enough evidence out there now to suggest that apixaban might be the ideal medication for adults with atrial fibrillation. Of course, that’s a general rule and each patient is unique.” If patients say they won’t take a twice-daily medication like apixaban, for instance, rivaroxaban—which is dosed once daily—remains a reasonable option, he added.

Deciding on a DOAC

Fralick said that when he sees patients with A-fib, the question isn’t whether to give warfarin or a direct oral anticoagulant (DOAC), it’s which DOAC to choose. Although there have not yet been any randomized trials comparing apixaban and rivaroxaban, the two most commonly prescribed DOACs, some prior studies have suggested that apixaban might have slightly better safety and efficacy compared with the other newer anticoagulants.

A 2012 study using indirect comparisons indicated that apixaban had a lower risk of major hemorrhage compared with other DOACs. And a 2018 analysis based on claims data showed that apixaban carried lower risks of stroke/systemic embolism and major bleeding compared with rivaroxaban and dabigatran (Pradaxa; Boehringer Ingelheim).

To further explore the issue, Fralick et al turned to the Optum Clinformatics database of commercial healthcare claims. Most patients were covered by employer-sponsored insurance, but 10% received coverage through Medicare Advantage plans. The analysis included patients who received a new diagnosis of atrial fibrillation or flutter and were started on either apixaban 5 mg (n = 59,172) or rivaroxaban 20 mg (n = 40,706) between December 28, 2012, and January 1, 2019. After propensity-score matching, there were 39,351 matched patient pairs (mean age 69 years; 40% women).

Mean follow-up was 288 days in the apixaban group and 291 days in the rivaroxaban group. During that time, new users of apixaban had lower ischemic and bleeding risks.

The investigators also examined risks of hepatitis and vasculitis because of case reports suggesting elevated risks of both outcomes with rivaroxaban. There were, however, no significant differences between groups.

Fralick et al also looked at risks of heart failure as a negative control because that risk is expected to be similar in patients treated with either apixaban or rivaroxaban; indeed, risk did not differ between groups. “This finding provides reassurance that our analyses were internally valid but, of course, does not guarantee it because the risk factors for heart failure and our study outcomes may differ,” the authors write in their paper.

What Explains Apixaban Advantage?

Asked what might explain the better safety and effectiveness seen with apixaban, Fralick pointed to prior pharmacokinetic studies showing that apixaban appears to have more stable levels in the blood compared with rivaroxaban. “Because the levels of rivaroxaban are a bit more erratic, that might potentially explain why we found a lower rate of bleeding as well as a lower rate of stroke with apixaban,” he explained.

Commenting for TCTMD, Margaret Fang, MD (University of California, San Francisco), said this study, though it has all of the limitations inherent to observational analyses, “is another point in favor of apixaban, at least over rivaroxaban, in terms of both safety and efficacy.”

Fang said that when choosing among the DOACs in her practice, potential differences in safety and efficacy are not the most important considerations. The top two factors that go into the decision are whether patients can afford a certain medication (and whether it’s covered by their insurance) and whether they can remain adherent to treatment. “If a patient is only going to take a once-a-day med and that’s the schedule that they can adhere to, then I think even if apixaban had somewhat better outcomes in this study I would pick the medication that they can most adhere to,” Fang said.

But, she continued, “if those are met and all else being equal, then between the two I think with this paper and with some of the prior studies apixaban may have an edge over rivaroxaban.” Thus, Fang said, “I think it’s reasonable to consider apixaban first for patients with atrial fibrillation.”

Fang also took a broader view to put the findings into context, noting that rates of ischemic and bleeding events were low overall and that differences between apixaban and rivaroxaban were not that great.

“Probably the larger take home is that for anticoagulants in general, if you can take one it is better than taking nothing for people with atrial fibrillation who are at higher risk for stroke,” she concluded.