October 03, 2016
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Xarelto associated with increased bleeding, mortality compared with Pradaxa

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Xarelto was linked to increases in both incracranial and extracranial bleeding in elderly adults being treated for nonvalvular atrial fibrillation compared with Pradaxa, according to data published in JAMA Internal Medicine.

Xarelto (rivaroxaban, Janssen) also reduced risk of thromboembolic stroke and increased risk for mortality compared with Pradaxa (dabigatran, Boehringer-Ingelheim), David J. Graham, MD, MPH, from the Center for Drug Evaluation and Research at the FDA, and colleagues found. However, the increase in intracranial hemorrhage due to treatment with rivaroxaban outweighed reductions in thromboembolic stroke.

"Warfarin sodium, a vitamin K antagonist, has been a mainstay of therapy to reduce thromboembolic stroke risk in patients with atrial fibrillation (AF), but it substantially increases the risk of intracranial and extracranial hemorrhage and it can be difficult to maintain patients in the therapeutic range," Graham and colleagues wrote. "Dabigatran etexilate mesylate, a direct thrombin inhibitor, and rivaroxaban, a factor Xa inhibitor, are non–vitamin K antagonist oral anticoagulants, which are simpler to dose than warfarin and do not require therapeutic monitoring."

They noted that previous research had not definitively concluded whether dabigatran and rivaroxaban "are therapeutically similar or whether clinically important differences exist that might lead prescribers and patients to prefer one over the other."

Graham and colleagues conducted a retrospective new-user cohort study of 118,891 patients who were enrolled in fee-for-service Medicare. The participants were aged at least 65 years and had nonvalvular AF. They began treatment with either rivaroxaban (20 mg, once daily) or dabigatran (150 mg, twice daily) between November 2011 and June 2014.

The researchers reported that 52,240 patients were treated with dabigatran and 66,651 patients were treated with rivaroxaban.

Results showed that, compared with dabigatran, rivaroxaban was associated with increases in mortality (HR = 1.15; 95% CI, 1-1.32; P = .051), reductions in thromboembolic stroke (HR = 0.81; 95% CI, 0.65-1.01; P = .07), increases in intracranial hemorrhage (HR = 1.65; 95% CI, 1.2-2.26; P = .002) and major extracranial bleeding (HR = 1.48; 95% CI, 1.32-1.67; P < .001), which included major gastrointestinal bleeding (HR = 1.4; 95% CI, 1.23-1.59; P < .001).

They also noted that rivaroxaban was associated with significantly increased mortality in patients aged at least 75 years or patients with a CHADS2 score of at least two.

"In this large direct comparison of patients with AF treated with dabigatran or rivaroxaban, rivaroxaban use was associated with statistically significant increases in the risk of [intracranial hemorrhage and major extracranial bleeding, including major gastrointestinal bleeding, and possibly with increased mortality in older patients or those with higher baseline risk of stroke," Graham and colleagues concluded. "The greater anticoagulant effect observed with rivaroxaban treatment may be due to the higher dose required for once-daily dosing. A contribution to this effect by off-label use of standard-dose rivaroxaban in patients with impaired renal function cannot be excluded." – by Chelsea Frajerman Pardes

Disclosure: The authors report no relevant financial disclosures.