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April 13, 2019Annals of Neurology109 citationsOpen Access

Direct oral anticoagulants versus vitamin K antagonists after recent ischemic stroke in patients with atrial fibrillation

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DSDavid SeiffgeMPMaurizio PaciaroniDWDuncan Wilson

Key Result

DOACs after recent cerebral ischemia in atrial fibrillation were associated with a reduced risk of recurrent ischemic stroke, ICH, or mortality compared to VKAs (HR 0.82; 95% CI 0.67-1.00; p=0.05).

Study Design

Type

Meta-Analysis (n=4,912)

Multicenter

Yes

Structured PICO

Do direct oral anticoagulants reduce the composite of recurrent ischemic stroke, intracerebral hemorrhage, or mortality compared to vitamin K antagonists in patients with atrial fibrillation and recent cerebral ischemia?

P
Population
4,912 patients (median age 78, 47.5% women) with atrial fibrillation and recent cerebral ischemia, followed for a total of 5,970 patient-years.
E
Exposure
Direct oral anticoagulants (DOACs) started at a median of 5 days after index event
C
Comparator
Vitamin K antagonists (VKAs) started at a median of 5 days after index event
O
Outcome
Composite of recurrent ischemic stroke (AIS), intracerebral hemorrhage (ICH), or mortalitycomposite

In patients with atrial fibrillation and recent cerebral ischemia, early DOAC treatment is associated with a reduced risk of the composite of recurrent stroke, ICH, or mortality compared to VKAs, largely driven by fewer ICH events.

Main Result

Hazard Ratio: 0.82 (95% CI 0.67–1)

p-value: p=0.05

Abstract

OBJECTIVE: We compared outcomes after treatment with direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and a recent cerebral ischemia. METHODS: We conducted an individual patient data analysis of seven prospective cohort studies. We included patients with AF and a recent cerebral ischemia (<3 months before starting oral anticoagulation) and a minimum follow-up of 3 months. We analyzed the association between type of anticoagulation (DOAC versus VKA) with the composite primary endpoint (recurrent ischemic stroke AIS, intracerebral hemorrhage ICH, or mortality) using mixed-effects Cox proportional hazards regression models; we calculated adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs). RESULTS: We included 4, 912 patients (median age, 78 years interquartile range IQR, 71-84; 2, 331 47. 5% women; median National Institute of Health Stroke Severity Scale at onset, 5 IQR, 2-12) ; 2, 256 (45. 9%) patients received VKAs and 2, 656 (54. 1%) DOACs. Median time from index event to starting oral anticoagulation was 5 days (IQR, 2-14) for VKAs and 5 days (IQR, 2-11) for DOACs (p = 0. 53). There were 262 acute ischemic strokes (AISs; 4. 4%/year), 71 intracranial hemorrrhages (ICHs; 1. 2%/year), and 439 deaths (7. 4%/year) during the total follow-up of 5, 970 patient-years. Compared to VKAs, DOAC treatment was associated with reduced risks of the composite endpoint (HR, 0. 82; 95% CI, 0. 67-1. 00; p = 0. 05) and ICH (HR, 0. 42; 95% CI, 0. 24-0. 71; p < 0. 01) ; we found no differences for the risk of recurrent AIS (HR, 0. 91; 95% CI, 0. 70-1. 19; p = 0. 5) and mortality (HR, 0. 83; 95% CI, 0. 68-1. 03; p = 0. 09). INTERPRETATION: DOAC treatment commenced early after recent cerebral ischemia related to AF was associated with reduced risk of poor clinical outcomes compared to VKA, mainly attributed to lower risks of ICH. ANN NEUROL 2019;85: 823-834.

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Cite This Study

Seiffge et al. (2019) conducted a meta-analysis in Atrial fibrillation and recent cerebral ischemia (n=4,912). Direct oral anticoagulants (DOACs) vs. Vitamin K antagonists (VKAs) was evaluated on Composite of recurrent ischemic stroke (AIS), intracerebral hemorrhage (ICH), or mortality (HR 0.82, 95% CI 0.67-1.00, p=0.05). DOACs after recent cerebral ischemia in atrial fibrillation were associated with a reduced risk of recurrent ischemic stroke, ICH, or mortality compared to VKAs (HR 0.82; 95% CI 0.67-1.00; p=0.05).

synapsesocial.com/papers/6a7f0b41cb17bc2d1d0d339ehttps://doi.org/10.1002/ana.25489
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