Cardiology Resident II University of California, Davis Davis, California, United States
Abstract:
Background: Feline cardiogenic arterial thromboembolism has a recurrence rate of approximately 36% with clopidogrel monotherapy. Studies suggest that dual antithrombotic therapy (DAT) with clopidogrel and rivaroxaban is superior to treatment with clopidogrel alone. Whether DAT with clopidogrel and apixaban yields similar synergistic effects remains unknown.
Hypothesis/
Objectives: We compared the safety and antithrombotic effects of clopidogrel monotherapy versus DAT with rivaroxaban or apixaban.
Animals: Ten healthy, purpose-bred, mixed-breed, domestic cats.
Methods: In this blinded, randomized, ex vivo crossover design, cats received seven days each of clopidogrel (18.75 mg PO q24h), clopidogrel plus rivaroxaban (2.5 mg/cat PO q24h; 0.42-0.68 mg/kg), and clopidogrel plus apixaban (1.25 mg/cat PO q12h; 0.21-0.34 mg/kg), followed by seven days of placebo. Post-treatment, platelet activation, aggregation, platelet-dependent thrombin generation, prothrombin time (PT), and activated partial thromboplastin time (aPTT) were evaluated.
Results: No cats exhibited adverse effects. Unlike clopidogrel monotherapy, DAT with rivaroxaban or apixaban suppressed maximum adenosine diphosphate (ADP)-induced platelet aggregation compared to placebo (p = 0.029 and p = 0.011, respectively). Clopidogrel monotherapy and DAT with rivaroxaban significantly inhibited ADP-induced platelet activation compared to placebo (p = 0.014 and p = 0.049, respectively). Only DAT with rivaroxaban significantly prolonged time to platelet-dependent thrombin generation (p = 0.029), time to 50% platelet-dependent thrombin generation (p = 0.035), PT (p = 0.0029), and aPTT (p = 0.0065) compared to clopidogrel monotherapy.
Conclusions: DAT safely decreases platelet activation, aggregation, and thrombin generation. Rivaroxaban-based DAT exerts greater synergistic antithrombotic effects than apixaban-based DAT compared to clopidogrel monotherapy at published doses.
