Acute Ischemic Stroke, Atrial Fibrillation, and Effect of Anticoagulation

Study Questions:

What is the risk of recurrent ischemic embolic events and severe bleeding in patients with acute stroke and atrial fibrillation (AF)?

Methods:

RAF (Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation) was a prospective observational study performed between January 2012 and March 2014, which enrolled consecutive patients with acute ischemic stroke and known or newly diagnosed AF without contraindications to anticoagulation. Physicians were free to decide the type of anticoagulant treatment (low molecular weight heparin [LMWH] or oral anticoagulants), as well as the day to initiate it. The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracranial bleeding within 90 days from acute stroke.

Results:

Of the 1,029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health (NIH) Stroke Scale, large ischemic lesion, and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4-14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio, 0.53 (95% confidence interval, 0.30–0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with LMWHs alone or followed by oral anticoagulants, respectively (p = 0.003).

Conclusions:

The authors concluded that acute stroke in AF patients is associated with high rates of ischemic recurrence and major bleeding at 90 days.

Perspective:

This study reports that acute stroke in AF is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study also indicates that high CHA2DS2-VASc score, high NIH Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleeding. It appears that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4-14 days from stroke onset. Furthermore, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with LMWHs alone or before oral anticoagulants. A randomized study assessing the efficacy of direct oral anticoagulants in the acute phase of stroke in patients with AF would provide additional insight.

Keywords: Anticoagulants, Arrhythmias, Cardiac, Atrial Fibrillation, Cerebral Hemorrhage, Embolism, Hemorrhage, Heparin, Low-Molecular-Weight, Ischemic Attack, Transient, Secondary Prevention, Stroke


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