Rajbeer Singh Sangha, MD

Paciaroni M, Agnelli G, Falocci N, Caso V, Becattini C, Marcheselli S, et al. Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation: Effect of Anticoagulation and Its Timing: The RAF Study. Stroke. 2015 

The authors of this study tackled an important question and one that has always been a grey area for stroke neurologists. They looked to answer the question of when anticoagulation should be initiated following a cardioembolic stroke. This international prospective multicenter study looked at three main questions which included the risk of recurrent ischemic events and bleeding following a cardioembolic stroke, the risk factors which are associated with these events and finally what is the rate of recurrence and bleeding when anticoagulation has been initiated.

The study looked at 1029 patients out of which 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or TIA or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding and 14 (1.4%) major extracranial bleeding. Primary study outcome looked at recurrent ischemic cerebrovascular events (stroke or TIA) and symptomatic systemic Embolisms and also symptomatic cerebral bleedings and major extra-cerebral bleeding at 90 days. At 90 days, 50% of the patients were either deceased or disabled (mRS≥3), and 10.9% were deceased. Factors predictive of the primary study outcomes included CHA2DS2-VASc score, high NIHSS, large ischemic lesion and type of anticoagulant. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared to initiating treatment before the aforementioned time period. About 7% of the patients treated with oral anticoagulants alone had an outcome event compared to 16.8% and 12.3% of the patients treated with low molecular weight heparins (LMWHs) alone or followed by oral anticoagulants, respectively (p=0.003).

Patients who received a direct oral anticoagulant were found to have low risks for both
symptomatic intracranial bleeding (2.1%) and ischemic event (4.3%), suggesting the need for further testing the new class of novel anticoagulant drugs in the acute phase of ischemic stroke in patients with AF. The advent of the novel anticoagulants has allowed for a reduction not only in ischemic events secondary to AF but also reduced bleed rates and thus I ask how far can we push the boundaries of starting these medications before we run into greater risks than benefits. This topic continues to be one of contention as the point in time to start anticoagulation is likely to be stratified secondary to multiple factors; perhaps a composite score should be created and tested in future studies.