Monthly Archives: August 2020

Kevin O’Connor, MD

Mikulík R, Eckstein J, Pearce LA, Mundl H, Rudilosso S, Olavarría VV, Shoamanesh A, Chamorro Á, Martí-Fàbregas J, Veltkamp R, et al. Frequency and Predictors of Major Bleeding in Patients With Embolic Strokes of Undetermined Source: NAVIGATE-ESUS Trial. Stroke. 2020;51:2139-2147.

About a third of ischemic strokes are categorized as being cryptogenic. Embolic strokes of unknown source (ESUS) represent a subset of these cryptogenic strokes. Clinicians are often faced with choosing between an anticoagulant and a platelet antiaggregant as one component of secondary prevention in patients having an ESUS. The NAVIGATE-ESUS trial provides data on the frequency and predictors of major bleeding in ESUS patients based on antithrombotic therapy choice, which can help inform treatment decisions.

NAVIGATE-ESUS was an international, double-blind, phase III trial that included 7213 participants from 31 countries who were randomized to receive rivaroxaban 15 mg once daily or aspirin 100 mg once daily. Sites were in Europe, East Asia, North America, and Latin America. The primary outcome of this analysis was major bleeding. Clinically-relevant nonmajor bleeding (CRNMB) was excluded for several reasons: CRNMB determinations were not determined centrally, whereas there was centralized adjudication of major bleeding events; intracranial bleeding was not considered to be a CRNMB; and analysis of independent predictors of major bleeding and CRNMBs such as epistaxis requiring medical attention would have been potentially spurious. NAVIGATE-ESUS was terminated before targeted enrollment was completed after an interim analysis found increased bleeding among rivaroxaban-treated participants, but no reduction in recurrent stroke.

Song J. Kim, MD

Mac Grory B, Nackenoff A, Poli S, Spitzer SM, Nedelmann M, Guillon B, Preterre C, Chen CS, Lee AW, Yaghi S, et al. Intravenous Fibrinolysis for Central Retinal Artery Occlusion: A Cohort Study and Updated Patient-Level Meta-Analysis. Stroke. 2020;51:2018–2025.

Patients presenting with complete retinal artery occlusion (CRAO), often first evaluated by ophthalmologists, are advised to seek emergent neurological evaluation. On the receiving end, even when the patient arrives within the typical thrombolysis window of <4.5 hours, some vascular neurologists may demur on offering reperfusion therapy owing to : 1) lack of robust evidence with regards to outcomes, and 2) absence of a comprehensive ophthalmological evaluation in excluding other non-ischemic differentials. 

To address the above, Mac Grory and co-authors developed a protocol for a rapid evaluation of CRAO including a dilated ophthalmologic evaluation and other work-up, ruling out mimics such as optic neuritis, giant cell arteritis, and retinal detachment. Barring any contraindications, patients received tPa if CRAO was deemed the most likely diagnosis, with visual acuity of less than 20/200 in the affected eye and presenting within 4.5 hours of symptom onset. Over a 10-year time span, 112 were diagnosed with acute CRAO. They were subsequently included in a retrospective observational analysis on post-tPa visual outcomes, as well as an updated subject-level meta-analysis expanding upon the authors’ 2015 study.

Elena Zapata-Arriaza, MD
@ElenaZaps

Johnston SC, Amarenco P, Denison H, Evans SR, Himmelmann A, James S, Knutsson M, Ladenvall P, Molina CA, Wang Y, for the THALES Investigators. Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA. N Engl J Med. 2020;383:207-217.

Without urgent treatment, the risk of major stroke in the week after a transient ischemic attack (TIA) or minor stroke can be as high as 10%. Some studies have shown that the combination of aspirin (ASA) plus Clopidogrel reduces the risk of stroke and other major ischemic events. Given the limitations in Clopidogrel due to hepatic conversion and the high resistance rates, Ticagrelor emerges as an interesting alternative, not dependent on metabolic activation.

With the aim of testing the effect of Ticagrelor and aspirin combination on stroke prevention, Johnston et al performed this randomized, placebo-controlled, double-blind trial involving patients who had had a mild-to-moderate acute noncardioembolic ischemic stroke, with a NIHSS≤5 or TIA, and who were not undergoing thrombolysis or thrombectomy. The patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive a 30-day regimen of either Ticagrelor (180-mg loading dose followed by 90 mg twice daily) plus aspirin (300 to 325 mg on the first day followed by 75 to 100 mg daily) or matching placebo plus aspirin. The primary outcome was a composite of stroke or death within 30 days. Secondary outcomes were first subsequent ischemic stroke and the incidence of disability within 30 days. The primary safety outcome was severe bleeding.

Richard Jackson, MD

Mac Grory B, Nackenoff A, Poli S, Spitzer MS, Nedelmann M, Guillon B, Preterre C, Chen CS, Lee AW, Yaghi S, et al. Intravenous Fibrinolysis for Central Retinal Artery Occlusion: A Cohort Study and Updated Patient-Level Meta-Analysis. Stroke. 2020;51:2018–2025.

Mac Grory et al. have published data that all stroke neurologists on call have been waiting for. In hospital systems where there are ophthalmologists taking calls, usually the neurologist on call for stroke gets the stroke code page for acute onset loss of vision or the patient is referred to the ER for a diagnosis of CRAO for evaluation. There is an ensuing debate between the on-call neurologist and ER physician about what to do for this patient. As neurologists, we are taught that the eye is an extension of the brain, and infarcts to the eye are technically infarcts to the brain. However, there is no data on whether or not thrombolysis with alteplase is efficacious. The ophthalmologists cite a lack of efficacy in trials and only one randomized trial with a small sample of 25 that showed no benefit when treated with standard dose 0.9mg/kg IV-tPA but within 24 hours of onset. An even more difficult situation arises in the primary stroke centers that do not have ophthalmologists on call where the neurologist on call for stroke has to make a decision based on clinical judgement. Both of these scenarios usually end in poor visual acuity for the patient after medical treatment with monotherapy or dual therapy antiplatelet with or without permissive hypertension and statin treatment.