ROCKET AF: Adverse outcomes related to major bleeding similar for Xarelto, warfarin

DALLAS — In patients with nonvalvular atrial fibrillation, outcomes after a major bleeding event were similar for patients assigned rivaroxaban and those assigned warfarin, according to a new analysis of data from the ROCKET AF study.

Researchers also found that major bleeding in patients assigned rivaroxaban (Xarelto, Janssen Pharmaceuticals) did not require greater transfusion of fresh frozen plasma or coagulation factors compared with those assigned warfarin, Jonathan P. Piccini, MD, of Duke University Medical Center, said during a presentation at AHA 2013.

Concern about bleeding

Piccini told Cardiology Today this finding is important because “we now have data from multiple mega trials showing that the novel oral anticoagulants are as effective as warfarin and have additional advantages, including ease of dosing, limited drug-drug and food-drug interactions, ease of monitoring and, very importantly, a reduction in intracranial and fatal bleeding.

Jonathan P. Piccini

“However, there’s still a great deal of anxiety and concern on the part of clinicians because there is no readily available antidote to these compounds. People are concerned that when patients do develop bleeding on these agents, the bleeding episodes may be difficult or impossible to manage. We were interested in the question of once people had a major bleeding event, what were the outcomes after that.”

For the study, patients with nonvalvular AF (n=14,264) were randomly assigned rivaroxaban or dose-adjusted warfarin. During the study period (median follow-up 1.9 years), 779 patients experienced major bleeding.

Outcomes after a major bleeding event, including stroke, non-central nervous system embolism and all-cause death were similar between the groups (HR for rivaroxiban vs. warfarin=0.68; 95% CI, 0.45-1.04).

Outcomes after bleeding similar

Major bleeding in those assigned rivaroxaban did not require greater transfusion of fresh frozen plasma or coagulation factors compared with those assigned warfarin (45 units vs. 81 units; OR=0.43; 95% CI, 0.29-0.66). Prothrombin complex concentrates were administered less often in the rivaroxaban arm (0.9%) compared with the warfarin arm (2.2%). Only one patient in the rivaroxaban arm received factor VIIa, factor VIII or factor IX within 1 day of major bleeding, compared with five in the warfarin arm.

In addition, hospitalization after bleeding events occurred at a lower rate in the rivaroxaban arm, Piccini told Cardiology Today.

“The worry that patients who experience a major bleed on these drugs are going to do worse is not supported by the data at all,” Piccini said in an interview. “It appears that outcomes are similar after a major bleed regardless of what agent people are receiving. The value of this analysis is that we have an answer for clinicians who may have been reluctant to treat their patients with novel oral anticoagulants and ask if their patients would be better off on warfarin. The answer is no, they are not better off on warfarin.” – by Erik Swain

For more information:

Piccini JP. Abstract #15879. Presented at: the American Heart Association Scientific Sessions; Nov. 16-20, 2013; Dallas.

Disclosure: The original ROCKET AF study was funded by Bayer Healthcare and Johnson & Johnson. Piccini reports financial ties with Arca BioPharma, Boston Scientific, GE Healthcare, Johnson & Johnson and Medtronic.