160 Are there Differential Effects of the Novel Oral Anticoagulants on Global Thrombotic Status?

Abstract

Background Novel oral anticoagulants (NOAC) are licensed for the prevention of stroke and systemic embolism in patients with atrial fibrillation (AF). There has been no head-to-head comparison of these agents. The effect of these agents on global thrombotic status, and the relative effects of the different NOACs, is unknown. We aimed to assess the relative and absolute effect of NOACs and warfarin (VKA) on global thrombotic status. Methods We tested the thrombotic profile of 80 patients (61% male, age 72 ± 12 years) with newly diagnosed AF at baseline, and in response to different oral anticoagulant regimens. Patients were anticoagulated with apixaban (n = 20), dabigatran (n = 20), rivaroxaban (n = 20), or warfarin (n = 20). Assessment of thrombotic status was performed using the Global Thrombosis Test (GTT), an automated point-of-care test that assesses both platelet reactivity and endogenous thrombolysis from a native, non-anticoagulated blood sample. The time taken to form an occlusive thrombus under high shear stress (occlusion time, OT), and the time required to restore flow through endogenous thrombolysis (lysis time, LT) were measured at baseline and after being established on stable anticoagulation. Results Oral anticoagulation increased OT (419 ± 122s vs. 584 ± 153s; p = 0.00001), and reduced LT (1922 ± 820s vs. 1615 ± 936s; p = 0.01). Although all anticoagulant regimens prolonged OT, the relative prolongation of the OT from baseline was lower with apixaban than with other NOACs or VKA (apixaban 94 ± 135s, dabigatran 185 ± 149s, rivaroxaban 199 ± 104s, warfarin 184 ± 149s; p = 0.06). Apixaban reduced LT from baseline (2056 ± 568s vs. 1313 ± 885s; p = 0.003), but no reduction in LT was observed with other NOACs or VKA. Patients in the dabigatran group were younger than in other groups (65 ± 11; p = 0.006), but otherwise the groups were well matched for sex, diabetes, hypertension, platelet count, haematocrit and fibrinogen levels, and CHA²DS²VASc score. Conclusions All oral anticoagulants (OACs) prolong OT. Apixaban causes relatively less prolongation of OT than other OACs and also reduces LT. The relatively small increase in OT with apixaban compared to other OACs may explain the observed lower incidence of GI bleeds in large trials with this agent.