Risk of Recurrent Ischemic Stroke with Unintended Low-Dose Oral Anticoagulant Therapy and Optimal Timing of Review

Abstract

Direct oral anticoagulant (DOAC) dose is adjusted according to manufacturer's recommendations when introduced. However, subsequent changes from appropriate DOAC doses to "unintended" inappropriate low-dose DOAC (ILD) due to increased body weight (BW) or decreased serum creatinine concentration might be overlooked. We investigated outcomes in patients receiving appropriate DOAC, "intended" ILD, or unintended ILD, to determine the optimal review time for DOAC doses and associated factors. This single-center, retrospective cohort study included inpatients receiving apixaban for stroke prevention between August 2015 and July 2017. Primary outcome was whether starting DOAC dose was selected according to manufacturer's recommendations and whether that dose remained appropriate thereafter. Secondary outcome was the incidence of recurrent ischemic stroke and intracranial bleeding during therapy. Average rates of change in BW, creatinine, and creatinine clearance (CrCl) were evaluated after hospitalization every 10 ± 3 days. During the study period, 120 patients received apixaban; 112 (93.3%) commenced appropriate DOAC doses, and 8 (6.7%) commenced intended ILD doses. Of the 112 patients on appropriate DOAC doses, 7 (6.3%) changed to unintended ILD doses because of increased BW (n = 4) or decreased creatinine (n = 3). The rate of recurrent ischemic stroke differed significantly between the appropriate DOAC dose and the intended or unintended ILD dose group (1.9% [2 of 105] versus 20.0% [3 of 15], P = .014). BW and renal function had stabilized after 20 ± 3 days posthospitalization. Receiving ILD doses, especially unintended, might be a risk factor for recurrent ischemic stroke and DOAC dose should be reviewed around 20 ± 3 days posthospitalization.