Anti-xa activity and event risk in patients with direct factor xa inhibitors initiated early after stroke

Background: Measuring anti-Xa activity (AXA) has been reported as useful for predicting future risk of hemorrhagic and ischemic events in stroke patients taking direct factor Xa inhibitors. We evaluated AXA levels of rivaroxaban or apixaban in acute stroke patients with non-valvular atrial fibrillation. Methods and Results: This was a single-center, prospective, observational study. Consecutive patients with acute ischemic stroke or transient ischemic attack who were admitted within 7 days of onset and started taking rivaroxaban or apixaban for NVAF between January 2012 and April 2017 were enrolled. AXA was measured at 2 time points: just before (AXA_trough) and 4 h after (AXA_peak) taking rivaroxaban or apixaban on the 2nd day or later of administration. Of 156 patients taking rivaroxaban, hemorrhagic events occurred in 13. Patients with hemorrhagic events had higher AXA_peak than those without [median (interquartile range): 1.93 (1.11–3.75) vs. 1.35 (0.80–2.00) IU/mL; P<0.01]. Multivariable-adjusted Cox models showed that AXA_peak was independently related to the incidence of hemorrhagic events. Of 169 patients taking apixaban, hemorrhagic events occurred in 11. Patients with hemorrhagic events had higher AXA_trough [2.78 (1.90–3.53) vs. 1.42 (0.93–2.08) IU/mL, P<0.01] and AXA_peak [4.05 (3.44–4.72) vs. 2.43 (1.79–3.35) IU/mL, P<0.01] than those without. Both AXA_trough and AXA_peak were independently related to the incidence of hemorrhagic events. Conclusions: In these patients who started rivaroxaban or apixaban early after stroke, AXA levels in the early period were related to future hemorrhagic events.