Inhibitory effects of dual antithrombotic therapy by rivaroxaban and clopidogrel on platelet function in cats

Hypertrophic cardiomyopathy (HCM) is the most common feline cardiac disease. Cats with HCM are at risk of arterial thromboembolism, an often-fatal event with poor prognosis. Despite this outcome, little is known about the synergistic inhibitory effects of rivaroxaban and clopidogrel on platelet function. We aim to examine the safety and efficacy of dual antithrombotic treatment using rivaroxaban and clopidogrel in comparison to either rivaroxaban or clopidogrel treatment. We hypothesize that dual treatment safely reduces platelet-dependent thrombin generation, platelet activation, and platelet aggregation more effectively than single agent treatment of rivaroxaban or clopidogrel in cats. Platelet parameters were compared before and after 7 days of rivaroxaban (2.5mg PO q24h), clopidogrel (18.75mg PO q24h), or dual treatment. Thrombin generation on platelet rich plasma was measured by fluorogenic thrombin generation assay. Platelet activation, quantified by P-selectin expression, was measured by flow cytometry in the presence or absence of adenosine diphosphate (ADP). Platelet aggregation was measured by ADPinduced whole blood platelet aggregometry. Preliminary data showed no adverse events in cats receiving single agent rivaroxaban therapy. Rivaroxaban treatment lowered P-selectin expression in unstimulated platelets (Mean Fluorescence: 1157 ±197 vs 821 ±126, p=0.004) but augmented platelet responsiveness to ADP (Fold Change: 0.17 ± 0.095 vs. 0.40 ±0.21, p=0.002). Rivaroxaban prolonged (1683 s ±811 vs 3588 s ±812, p=0.01) and diminished (RFU: 5.13x107 ±4.20 vs 1.64 x107 ±1.09, p=0.004) thrombin generation. Rivaroxaban did not alter ADP-induced platelet aggregation. These findings suggest rivaroxcaban may indirectly inhibit platelet activation by modulating thrombin generation. Dual therapy data generation is ongoing.