Evaluation of the safety and tolerability of rivaroxaban in dogs with presumed primary immune-mediated hemolytic anemia

Objective - To evaluate the safety and tolerability of rivaroxaban (RIV), an oral direct factor Xa inhibitory drug, in dogs with presumed primary immune-mediated hemolytic anemia (pIMHA). Design - Prospective, multicenter, positive-controlled, unblinded clinical trial. Client-owned dogs were enrolled between October 2012 and March 2014. Setting - Private referral centers. Animals - Twenty-four client-owned dogs with pIMHA. Enrolled dogs were randomized in 2 treatment groups to receive by mouth RIV or clopidogrel (CL) and low-dose aspirin (LDA). All dogs were monitored for 90 days from the enrollment in the study. Interventions - Enrolled dogs were given a standardized immunosuppressive protocol and RIV or CL and LDA. Measurements and Main Results - There was no identifiable adverse drug reaction, evidence of hemorrhage, significant prolongation of prothrombin time or activated partial thromboplastin time, or increase in transfusion requirements associated with RIV therapy compared to CL and LDA in dogs with pIMHA. There was no significant difference between treatment groups with respect to thrombotic events, survival rates to discharge, at 1 month and 3 months from diagnosis. Conclusions - This study suggests that RIV at a median dose of 0.89 mg/kg by mouth once daily was safe and well tolerated in a small group of dogs with presumed pIMHA able to tolerate oral medications and treated with a standardized immunosuppressive treatment protocol. Conclusions regarding the relative efficacy of RIV as compared to CL and LDA cannot be made due to the small size of the treatment groups and because pharmacodynamic effects were not assessed.