Ischemic Stroke despite Oral Anticoagulant Therapy in Patients with Atrial Fibrillation

Abstract

Objective It is not known whether patients with atrial fibrillation (AF) with ischemic stroke despite oral anticoagulant therapy are at increased risk for further recurrent strokes or how ongoing secondary prevention should be managed. Methods We conducted an individual patient data pooled analysis of 7 prospective cohort studies that recruited patients with AF and recent cerebral ischemia. We compared patients taking oral anticoagulants (vitamin K antagonists [VKA] or direct oral anticoagulants [DOAC]) prior to index event (OAC prior ) with those without prior oral anticoagulation (OAC naive ). We further compared those who changed the type (ie, from VKA or DOAC, vice versa, or DOAC to DOAC) of anticoagulation (OAC changed ) with those who continued the same anticoagulation as secondary prevention (OAC unchanged ). Time to recurrent acute ischemic stroke (AIS) was analyzed using multivariate competing risk Fine–Gray models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results We included 5,413 patients (median age = 78 years [interquartile range (IQR) = 71–84 years]; 5,136 [96.7%] had ischemic stroke as the index event, median National Institutes of Health Stroke Scale on admission = 6 [IQR = 2–12]). The median CHA 2 DS 2 ‐Vasc score (congestive heart failure, hypertension, age≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65–74 years, sex category) was 5 (IQR = 4–6) and was similar for OAC prior (n = 1,195) and OAC naive (n = 4,119, p = 0.103). During 6,128 patient‐years of follow‐up, 289 patients had AIS (4.7% per year, 95% CI = 4.2–5.3%). OAC prior was associated with an increased risk of AIS (HR = 1.6, 95% CI = 1.2–2.3, p = 0.005). OAC changed (n = 307) was not associated with decreased risk of AIS (HR = 1.2, 95% CI = 0.7–2.1, p = 0.415) compared with OAC unchanged (n = 585). Interpretation Patients with AF who have an ischemic stroke despite previous oral anticoagulation are at a higher risk for recurrent ischemic stroke despite a CHA 2 DS 2 ‐Vasc score similar to those without prior oral anticoagulation. Better prevention strategies are needed for this high‐risk patient group. ANN NEUROL 2020;87:677–687

Long-Term Anticoagulation in Secondary Ischemic Stroke Prevention: The Prospective Multicenter RESTAIC Registry

“…Patients with previous stroke before the index stroke presented a significantly higher rate of stroke recurrence during the follow-up. It is well-known that these patients are at higher risk of ischemic events even if on OACs, and similar findings have been previously reported (40). This should encourage us to look for better strategies to improve secondary stroke prevention, such as ensuring patients' adherence to treatment.…”

Non-vitamin K oral anticoagulants for secondary stroke prevention in patients with atrial fibrillation

“… 28 An individual patient data analysis including 4912 patients treated with oral anticoagulation after recent cerebral ischaemia related to AF revealed the following major findings: First, treatment with NOACs commenced a median of 5 days after the index event has a lower risk of adverse outcomes compared to treatment with VKA; second, this benefit is mainly attributed to lower risks of ICH; and, third, the benefit is consistent across subgroups. 29 …”

Etiology of Ischemic Strokes of Patients with Atrial Fibrillation and Therapy with Anticoagulants

“…Notably, in the primary prevention analyses, ischemic strokes occurred 2.1 to 10.1 times more often than hemorrhagic strokes and 2.2 to 27.4 times more often in the secondary prevention cohorts [ 4 , 5 , 6 , 7 ]. Recently, a pooled analysis underlined that patients with AF and oral anticoagulation before stroke were at a higher risk of recurrent stroke than patients without anticoagulation [ 8 ]. Thus, reducing the number of recurrent ischemic strokes in patients with AF despite oral anticoagulation remains an important, yet largely unsolved challenge.…”