Acute Ischemic Events in Patient Receiving Direct Oral Anticoagulants for Atrial Fibrilation: Incidence, Outcome and Clinical Profile

Introduction

The use of direct oral anticoagulants (DOACs) is increasing for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). Despite the good efficacy/safety balance, clinicians will be confronted with patients under treatment with DOAC presenting with ischemic events. Currently, there is a paucity of data from investigational studies regarding the clinical profile, risk factors and most suitable therapeutic intervention after therapeutic failure with these anticoagulants.

Aims

To describe the clinical profile and assess the rate of subsequent ischemic events appearing during the course of anticoagulant therapy and tried to identify risk factors for these events in "real life" population treated with DOACs.

Methods

In this multicenter and retrospective study we included patients with NVAF who had recived DOACs. Ischemic Events during february 2013 to february 2016 was analyzed.

Results

We enrolled, 3353 patients with NVAF who had recived DOACs. During the course of anticoagulation (mean, 9.4 months), 39 patients (1.16%) developed ischemic events (stroke, 22; transient ischemic attack (TIA), 7; peripheral embolism, 10). Rate of ischemic events was 0.9/100 patient-years. Median age was 76 years (range: 51-92) and 25 (64.1%) were female. Among them, 19 patients received dabigatran, 14 rivaroxaban and 6 apixaban. As per the thrombotic risk score, 66.7% of the patients were classified as "high risk" (CHA2DS2-VASc score > 5). Thirty-eight patients (97.4%) received vitamin K antagonists (VKA) prior to use of DOAC. Ischemic events patients had a higher incidence of hypertention (94.9% ), diabetes (64.1%), history of previous ischemic stroke (74.4%) and therapeutic failure with VKA (79.5%). Nonadherence to treatment was identified only in 6 patients (15.4%). On multivariable analysis, previous ischemic stroke/ TIA (hazard ratio [HR], 1.77; 95% confidence interval [CI], 1.21-2.61), female sex (HR, 1.54; 95% CI, 1.05-2.26), and CHA2DS2-VASc score>5 (HR, 1.72; 95% CI, 1.25-2.36) were independently associated with the risk for ischemic events.

For the management of acute ischemic event, 20 patients received endovascular treatment, 12 patients switched from DOAC to unfractionated heparin or low molecular weight heparin and intravenous fibrinolysis was performed in 7 patients; intracranial hemorrhage being observed in two patients after treatment with thrombolytic therapy. Regarding the subsequent anticoagulation continuation at discharge, 19 patients switched to concomitant therapy with DOAC and antiplatelets, 12 patients to other DOAC and only 8 to VKA. There was a 5.1% 30 day mortality after ischemic event and 15.4% of patients had neurologic complications after ischemic event.

Conclusions

We described a low rate of stroke in patients treated with DOACs, but further studies are necessary in order to identify very high-risk patients with special emphasis in those with high CHA2DS2-VASC score, previous stroke and a correct anticoagulation.