Comparing the Novel Oral Anticoagulants: Effectiveness Similar, but Apixaban May Come With Less Bleeding

CHICAGO, IL—A study of administrative claims suggests that dabigatran, rivaroxaban, and apixaban perform similarly for preventing stroke or systemic embolism in patients with nonvalvular A-fib, although apixaban seems to carry a lower major bleeding risk compared with the other two drugs.

Event rates were low overall, however, with stroke or systemic embolism occurring at a rate of 1.02 to 1.21 per 100 person-years and major bleeding occurring at a rate of 2.01 to 4.55 per 100 person-years. Those figures are similar to what was seen in the pivotal clinical trials that compared these agents to warfarin, Peter Noseworthy, MD (Mayo Clinic, Rochester, MN), reported at the American College of Cardiology 2016 Scientific Sessions here.

The fact that clinicians in everyday practice are achieving results similar to what was seen in the trial setting is an important message of the study, according to Mintu Turakhia, MD (VA Palo Alto Health Care System, Palo Alto, CA), who served as co-chair of the session at which Noseworthy presented the findings.

But—though lauding the analytical approach used by the investigators—he told TCTMD that the observed differences between agents should be viewed cautiously. He said that many factors cannot be captured well in administrative databases, including the reasons a patient is given one drug over another, aspirin use, whether dosing is correct, and kidney function. Those last two factors in particular are major considerations when assessing bleeding risk, Turakhia said.

“The hard part from nonrandomized data is the ability to draw conclusive inferences from it,” even with propensity matching, which was used in the study, he said. Referring to the variation in major bleeding risk across agents, he added, “The fact is that the differences are so small in [absolute terms] that any one of these seemingly minor concerns could overturn the result, and that’s why you have to be very careful with your interpretation.”

Noseworthy and colleagues used claims data from the Optum Labs Data Warehouse to perform direct comparisons of dabigatran (Pradaxa; Boehringer Ingelheim), rivaroxaban (Xarelto; Janssen Pharmaceuticals), and apixaban (Eliquis; Bristol-Myers Squibb) in US patients with nonvalvular A-fib who initiated treatment between October 2010 and February 2015. The study did not include the newest oral anticoagulant to be approved, edoxaban (Savaysa; Daiichi Sankyo).

The researchers performed propensity matching, leaving more than 31,000 patients for the dabigatran versus rivaroxaban comparison and about 13,000 patients for the comparisons between apixaban—which has spent the least time on the market—and the other two drugs.

The primary effectiveness outcome was the composite of stroke or systemic embolism, and there were no significant differences observed between the three drugs. That finding was generally consistent in an analysis stratified by baseline risk defined by CHA₂DS₂-VASc and HAS-BLED scores, although one difference emerged: rivaroxaban had lower risk compared with dabigatran in patients with a CHA₂DS₂-VASc score of 2 or 3 (HR 0.44; 95% CI 0.23-0.85).

There were no trends favoring any one drug over the others for the secondary outcomes of ischemic or hemorrhagic stroke.

Turning to major bleeding—the primary safety outcome—rivaroxaban was associated with a higher risk compared with dabigatran (HR 1.30; 95% CI 1.10-1.53) and apixaban was associated with lower risk versus either dabigatran (HR 0.50; 95% CI 0.36-0.70) or rivaroxaban (HR 0.39; 95% CI 0.28-0.54). Baseline risk defined by HAS-BLED score did not seem to affect the findings.

For intracranial bleeding, the only between-drug difference to emerge was for rivaroxaban versus dabigatran (HR 1.79; 95% CI 1.12-2.86). Overall rates were very low, however, ranging from 0.25 to 0.53 per 100 person-years.

Choosing Among the Novel Anticoagulants

Turakhia said head-to-head randomized trials would be needed to definitively establish whether there are any differences in safety and effectiveness between these drugs, although both he and Noseworthy said such studies are unlikely. Turakhia noted that the manufacturers would not fund the trials because they would be taking a risk and that the trials would be very expensive for other entities like large healthcare systems or the National Institutes of Health.

Currently what goes into choosing among the newer agents are practical concerns, including copayments, familiarity that the prescribing clinician has with a certain drug, and dosing regimen, Turakhia said, adding that some patients have trouble taking medications twice a day (rivaroxaban is taken once daily and apixaban and dabigatran twice daily).

The decision is individualized based on the needs of the patient, he said, noting “that there’s not enough evidence to indicate that [the new oral anticoagulants are] so different that you wouldn’t tailor them.”

• Noseworthy PA. Direct comparison of dabigatran, rivaroxaban, and apixaban for effectiveness and safety in nonvalvular atrial fibrillation. Presented at: American College Cardiology 2016 Scientific Sessions. April 3, 2016. Chicago, IL.

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