J Stroke.  2024 Jan;26(1):13-25. 10.5853/jos.2023.01578.

Update of Anticoagulation Use in Cardioembolic Stroke With a Special Reference to Endovascular Treatment

• Safouris A
• Psychogios K
• Palaiodimou L
• Orosz P
• Magoufis G
• Kargiotis O
• Theodorou A
• Karapanayiotides T
• Spiliopoulos S
• Nardai S
• Sarraj A
• Nguyen TN
• Yaghi S
• Walter S
• Sacco S
• Turc G
• Tsivgoulis G

• KMID: 2551344
• DOI: http://doi.org/10.5853/jos.2023.01578

Abstract

Cardioembolic stroke is a major cause of morbidity, with a high risk of recurrence, and anticoagulation represents the mainstay of secondary stroke prevention in most patients. The implementation of endovascular treatment in routine clinical practice complicates the decision to initiate anticoagulation, especially in patients with early hemorrhagic transformation who are considered at higher risk of hematoma expansion. Late hemorrhagic transformation in the days and weeks following stroke remains a potentially serious complication for which we still do not have any established clinical or radiological prediction tools. The optimal time to initiate therapy is challenging to define since delaying effective secondary prevention treatment exposes patients to the risk of recurrent embolism. Consequently, there is clinical equipoise to define and individualize the optimal timepoint to initiate anticoagulation combining the lowest risk of hemorrhagic transformation and ischemic recurrence in cardioembolic stroke patients. In this narrative review, we will highlight and critically outline recent observational and randomized relevant evidence in different subtypes of cardioembolic stroke with a special focus on anticoagulation initiation following endovascular treatment. We will refer mainly to the commonest cause of cardioembolism, non-valvular atrial fibrillation, and examine the possible risk and benefit of anticoagulation before, during, and shortly after the acute phase of stroke. Other indications of anticoagulation after ischemic stroke will be briefly discussed. We provide a synthesis of available data to help clinicians individualize the timing of initiation of oral anticoagulation based on the presence and extent of hemorrhagic transformation as well as stroke severity.

Keyword

Ischemic stroke; Endovascular treatment; Anticoagulation; Symptomatic intracranial hemorrhage; Hemorrhagic transformation

Figure

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  Figure 1. A 70-year-old woman, with a history of arterial hypertension and diabetes mellitus, presented with intermittent vertigo and diplopia for 48 hours. The National Institutes of Health Stroke Scale (NIHSS) on admission was 4 and magnetic resonance imaging revealed multiple acute ischemic lesions on diffusion- weighted imaging (A). Digital subtraction angiography revealed a sub-occlusive intraluminal thrombus of the right vertebral artery in the V4 segment (B). The left posterior cerebral artery was occluded in the P1 segment but slow flow to the P2 segment was noted through a small posterior communicating artery. Thrombectomy was undertaken but was unsuccessful to recanalize the right vertebral artery. The cause of intraluminal thrombus was believed to be an underlying atherosclerotic plaque, since the patient was in sinus rhythm. The patient received clopidogrel and therapeutic dose of low-molecular weight heparin (LMWH) and was discharged 4 days later with NIHSS score of 1. She presented 2 weeks after discharge with right hemianopia and aphasia (NIHSS-score: 10 points). Paroxysmal atrial fibrillation was detected on electrocardiogram. Repeat brain computed tomography revealed an extensive lobar intracranial hemorrhage of the left occipital lobe (C). LMWH and clopidogrel were halted and the patient had a neurosurgical evacuation of the hematoma with good, but partial, recovery (NIHSS score of 6 points). She was treated with apixaban 5 mg bid 12 days after surgical evacuation.

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  Figure 2. A 63-year-old man with atrial fibrillation presented with acute left hemianopia and gait disturbance. Emergent magnetic resonance imaging revealed an acute ischemic lesion in the distribution of the right posterior cerebral artery (PCA) (A). Digital subtraction angiography revealed a complete basilar artery (BA) occlusion (B) that was recanalized with mechanical thrombectomy (C). Distal right PCA was left occluded given the extensive established infarction of the right occipital lobe (C). The patient was loaded with aspirin (500 mg) and clopidogrel (600 mg) and received a bolus of 5,000 units of unfractionated heparin and residual BA stenosis was treated with 2 intracranial stents (D). Computed tomography (CT) post-treatment showed extravasated contrast within the right occipital lobe infarction (E). The patient had abrupt neurological deterioration 20 hours after recanalization. Emergent CT revealed an extensive parenchymal hematoma type 2 originating from the right occipital lobe (F). The patient deceased hours later.

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  Figure 3. Day rules proposed for initiating anticoagulation after cardioembolic stroke/TIA and registries including patients post-EVT. Days refer to days after index event as the minimal delay for each stroke category to initiate anticoagulation. Mild AIS: NIHSS <8; Moderate AIS: NIHSS 8–15; Severe AIS: NIHSS >15; Small infarct size: Ischemic lesion ≤1.5 cm; Medium infarct size: NIHSS <8 and lesion in a cortical superficial branch of middle cerebral artery (MCA), or involving the MCA deep branch, or in internal border zone territories, or in a cortical superficial branch of posterior cerebral artery (PCA), or lesion involving the PCA branch or lesion in a cortical superficial branch of anterior cerebral artery (ACA); large infarct size: anterior circulation: lesion involving complete territory of MCA, PCA, or ACA or involving 2 cortical superficial branches of MCA or involving a cortical superficial branch of MCA associated to the MCA deep branch, or involving more than 1 artery territory (eg, MCA associated to ACA territories); posterior circulation: lesion involving brain stem or cerebellum >1.5 cm. TIA, transient ischemic attack; EVT, endovascular treatment; ESC, European Society of Cardiology; AIS, acute ischemic stroke; AHA/ASA, American Heart Association and American Stroke Association; ESO, European Stroke Organisation; HT, hemorrhagic transformation; HI, hemorrhagic infarction; PH, parenchymal hemorrhage; NIHSS, National Institutes of Health Stroke Scale.

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  Figure 4. Synthesis of available data for initiating anticoagulation (AC) after endovascular treatment (EVT). Starting non-vitamin K antagonist oral anticoagulants (NOACs) without bridging is possible at day 2 but may be safer at day 5, even in the context of hemorrhagic infarction. Delaying initiation at 7–14 days for patients with parenchymal hemorrhage may be safe. Aspirin should be given until NOAC initiation. ALESSA scores 3–4 should prompt earlier AC initiation.

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