Risk of hemorrhagic transformation with early use of direct oral anticoagulants after acute ischemic stroke: A pooled analysis of prospective studies and randomized trials

Abstract

Introduction: Precise risk of hemorrhagic transformation (HT) in acute ischemic stroke (AIS) remains unknown, leading to delays in anticoagulation initiation for secondary stroke prevention. We sought to assess the rate of HT associated with direct oral anticoagulant (DOAC) initiation within and beyond 48 hours post-AIS. Methods: A pooled analysis of DOAC initiation within 14 days of AIS or transient ischemic attack (TIA) was conducted with 6 studies (4 prospective open label treatment, blinded outcome studies and 2 randomized trials; NCT02295826 and NCT02283294). The primary endpoint was incident radiographic HT on follow-up imaging (day 7–30). Secondary endpoints included symptomatic HT, new parenchymal hemorrhage, recurrent ischemic events, extracranial hemorrhage, study-period mortality, and follow-up modified Rankin Scale score. The results were reported as odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI). Results: We evaluated 509 patients; median infarct volume was 1.5 (0.1–7.8) ml, and median National Institutes of Health Stroke Scale was 2 (0–3). Incident radiographic HT was seen on follow-up scan in 34 (6.8%) patients. DOAC initiation within 48 hours from index event was not associated with incident HT (adjusted OR 0.67, [0.30 – 1.50] P=0.32). No patients developed symptomatic HT. Conversely, 31 (6.1%) patients developed recurrent ischemic events, 64% of which occurred within 14 days. Initiating a DOAC within 48 hours of onset was associated with similar recurrent ischemic event rates compared to those in which treatment was delayed (HR 0.42, [0.17 – 1.008] P=0.052). In contrast to HT, recurrent ischemic events were associated with poor functional outcomes (OR=6.8, [2.84 – 16.24], p<0.001). Conclusions: In this pooled analysis, initiation of DOAC within 48 hours post-stroke was not associated with increased incident risk of HT, and none developed symptomatic HT. The analysis was underpowered to determine the effect of early DOAC use upon recurrent ischemic events.

Early Versus Late Initiation of Direct Oral Anticoagulants After Ischemic Stroke in People With Atrial Fibrillation and Hemorrhagic Transformation: Prespecified Subanalysis of the Randomized Controlled ELAN Trial

“…2,7 Recently published data from observational studies and 2 randomized controlled trials indicate that initiating anticoagulation treatment early, as opposed to later guideline-based initiation, not only is safe but also contributes to a reduction in recurrent ischemic events. 6,[8][9][10] However, it remains unclear whether early initiation of DOAC therapy is also advantageous in people known to have HT at treatment start because earlier studies either did not provide information on HT or had few participants with this condition. 6,8,9 This information carries considerable clinical relevance; clinicians frequently postpone the initiation of anticoagulation therapy when HT is detected on poststroke neuroimaging.…”

Application of radiomics in ischemic stroke

“…However, venous thrombolysis is often accompanied by the complication of intracerebral hemorrhage transformation. 43 To predict hemorrhage transformation, Meng et al. 44 introduced a multifaceted MRI radiomics-based model coupled with machine learning.…”

Diagnosis and Management of Atrial Fibrillation in Acute Ischemic Stroke in the Setting of Reperfusion Therapy: Insights and Strategies for Optimized Care

“…However, continuing anticoagulation in the acute setting of ischemic stroke is controversial, as it may increase the risk of haemorrhagic transformation (HT) [63]. The American Heart Association/American Stroke Association (AHA/ASA) recommends withholding anticoagulation for at least 24 h after IVT or EVT in patients with AF-related AIS, with early initiation of anticoagulation reserved for high-risk patients [13].…”