Alejandro Rodríguez-Vázquez, MD

Du H, Wilson D, Ambler G , Banerjee G, Shakeshaft C, Cohen H, Yousry T, Al-Shahi Salman R, Lip GYH, Houlden H, et al. Small Vessel Disease and Ischemic Stroke Risk During Anticoagulation for Atrial Fibrillation After Cerebral Ischemia. Stroke. 2021;52:91–99.

Atrial fibrillation (AF) is one of the most important risk factors associated with ischemic stroke, with a 4.7 to 7.7%/year risk of cerebrovascular events despite anticoagulation. These recurrences could be explained because of an inadequate anticoagulation or alternative stroke mechanisms such as small vessel disease (SVD).

The authors analyzed data from the CROMIS-2 study, a multicenter prospective inception cohort study of patients anticoagulated for AF after an ischemic stroke or transient ischemic attack. They included 1419 patients with MR imaging and a total follow-up of 24 months after the first cerebrovascular event. SVD was present in 768 (54.1%) patients, defined as the presence of ≥11 basal ganglia perivascular spaces (BGPV), ≥11 centrum semiovale perivascular spaces, cerebral microbleeds, lacunes and/or moderate to severe white matter hyperintensities (which included periventricular Fazekas grade 3 or deep white matter Fazekas grade ≥2).

Lukas Mayer, MD

Bonacina S, Grassi M, Zedde M, Zini A, Bersano A, Gandolfo C, Silvestrelli G, Baracchini C, Cerrato P, Lodigiani C, et al. Clinical Features of Patients With Cervical Artery Dissection and Fibromuscular Dysplasia. Stroke. 2021;52:821–829.

The search for characteristic features of underlying vasculopathy and/or connective tissue disease in patients with spontaneous cervical artery dissection has been going on for quite some time now, more recently yielding progress on multiple levels. Especially in vascular imaging, the coexistence of radiological hallmarks supposedly attributed to fibromuscular dysplasia (FMD) has been of interest in these subjects.

Through their recently published study, Bonacina et al. add to this interesting and highly relevant topic. The authors reviewed case files and imaging data of 1283 subjects enrolled in the multicenter Italian Project of Stroke in Young Adults Cervical Artery Dissection (IPSYS CeAD) study with the inclusion criterion being first-ever spontaneous cervical artery dissection (sCeAD) between January 2000 and June 2019. Through their work-up, they generated a cohort clinically consistent with most previously described sCeAD studies, as patients were in their mid 40s at sCeAD onset, males predominated, coexistent cerebrovascular risk factors were infrequent at baseline and cerebral ischemia was evident in more than 80% of sCeAD cases. Solely, the 60 to 40% split of internal carotid to vertebral artery affection might suggest an older sample of patients as more recent sCeAD-cohorts support an equal distribution of anterior and posterior circulation dissection. The latter has predominantly been attributed to the increased availability of advanced cerebrovascular imaging (e.g., 3T MRI – fat saturated T1 imaging). In 8% of subjects, according to the most recent expert consensus guidelines, vascular imaging was consistent with cerebrovascular FMD. Acute management and clinical manifestation did not differ in those with or without these signs. Subjects did, however, differ in some demographics and clinical characteristics, as those with imaging findings suggestive of FMD were more frequently women, more likely to have intracranial aneurysms and first-degree relatives with sCeAD. Upon follow-up, they also were more likely to have pseudoaneurysms, multivessel involvement of sCeAD and sCeAD recurrence. Bonacina et al. further describe pathophysiological mechanisms possibly linking migraine with aura, cerebrovascular FMD and sCeAD.

Kevin O’Connor, MD

Boulouis G, Hak JF, Kerleroux B, Benichi S, Stricker S, Gariel F, Alias Q, Bourgeois M, Meyer P, Kossorotoff M, et al. Hemorrhage Expansion After Pediatric Intracerebral Hemorrhage. Stroke. 2021;52:588-594.

Intracerebral hemorrhage (ICH), similar to most aspects of pediatric stroke, is not as well-studied as it is in adults, in part due to its lower incidence in children. Boulouis et al. retrospectively assessed a cohort of pediatric ICH patients at a single center in Paris, France (2000-2019). Various exclusion criteria reduced their patient population from 243 to 52. Of these children, 18 had hemorrhage expansion (HE; 34.6%) and 8 of these had significant hemorrhage expansion (sHE; 15.4%). Children with sHE were more likely to have coagulation disorders (50.0% versus 2.3%; P=0.022) and tended to more frequently have focal deficits on presentation, although the difference was not significant (75.0% versus 43.2%; P=0.08). Underlying coagulation disorders were independently associated with any HE (adjusted OR, 14.4 [95% CI, 1.04–217]; P=0.048).

Outcomes were assessed using the King’s Outcome Scale for Childhood Head Injury (KOSCHI) score at 12 months. Scores <5 were poor, with scores of 2-3 reflecting severe disabilities, and score of 1 representing death. Just under half of the 52 children had a poor outcome (n=21, 40.4%) with 8 being severely disabled or dying (15.4%). Significant HE was associated with poor outcome in general (adjusted OR, 6.01 [95% CI, 0.91–39.82]; P=0.048) and with severe disability or death in particular (adjusted OR 21.71 [95% CI, 3.35–140.64]; P=0.001).

Walter Valesky, MD

Labovitz AJ, Rose DZ, Fradley MG, Meriwether J, Renati S, Martin R, Kasprowicz T, Murtagh R, Kip K, Beck T, et al. Early Apixaban Use Following Stroke in Patients With Atrial Fibrillation: Results of the AREST Trial. Stroke. 2021;52:1164-1171.

In the era of direct oral anticoagulant (DOAC) therapy, a paucity of clinical trials exist guiding anticoagulation for atrial fibrillation (AF) after acute ischemic stroke (AIS). European Heart Rhythm Association guidelines promoted (by expert panel) a 1-3-6-12 day approach with anticoagulation started after 1 day in patients with a transient ischemic attack (TIA), after 3 days in those with small strokes, after 6 days in those patients with moderate strokes and approximately 2 weeks in those with large arterial distribution strokes._­¹ Guidelines from the American Heart Association are extremely broad and recommend starting anticoagulation after 4-14 days in patients with ischemic stroke.² Additionally, these recommendations are based on data that do not adequately reflect the current management of AF using DOACs.³ Labovitz et al. attempt to give clarity to this topic with an open-label, randomized trial to evaluate the safety of early use of apixaban in patients with recent stroke compared to warfarin. 

In the AREST trial, the authors enrolled patients with onset of symptoms of AIS or TIA within 3-5 days or within 3 days, respectively. These patients also had a history of AF or newly diagnosed AF confirmed using usual methods by an electrophysiologist. Once randomized, patients in the apixaban group were started on day 0-3 for TIA, day 3-5 for small-sized AIS (<1.5cm in largest dimension), and day 7-9 for medium-sized AIS (>1.5cm but less than a full vascular territory). Patients randomized to receive warfarin were started at 1-week post-TIA or 2 weeks post-stroke. Patients with large-sized AIS (entire vascular territory) and brainstem strokes were excluded. In addition, patients with obvious contraindications to anticoagulation use such as intracranial hemorrhage (ICH), hemorrhagic transformation, as well as those with AIS believed to be from non-embolic etiologies were excluded.

Kevin O’Connor, MD

Lefeber GJ, Knol W, Souverein PC, Bouvy ML, de Boer A, Koek HL. Statins After Ischemic Stroke in the Oldest: A Cohort Study Using the Clinical Practice Research Datalink Database. Stroke. 2021;52:1244–1252.

Statins are a component of usual care following ischemic stroke, but evidence for their initiation in patients age >80-years is limited. Lefeber et al. conducted an observational cohort study to examine the effect of statin initiation on recurrence of cardiovascular events and mortality in those age >80-years following a first stroke. They performed the same analyses on patients aged 65-80 for comparison.

Patients ≥80 and 65-80 had reductions in cardiovascular events when prescribed statins for > 2 years (≥80 adjusted HR, 0.70 [95% CI, 0.52–0.92]; 65-80 adjusted HR, 0.67 [95% CI, 0.49–0.91]) compared to no statin use. There was no significant difference in event rates for either cohort when treated for 1-2 years compared to untreated patients (≥80 adjusted HR, 0.79 [95% CI, 0.59–1.07]; 65-80 adjusted HR, 1.00 [95% CI, 0.69–1.46]). Using a statin for less than one year was associated with reductions in both groups (≥80 adjusted HR, 0.43 [95% CI, 0.29–0.41]; 65-80 adjusted HR, 0.43 [95% CI, 0.34–0.54]). Compared to < 2 years of statin use (or no use), there was a nonsignificant trend toward lower risk for the ≥80 cohort (adjusted HR, 0.80 [95% CI, 0.62–1.02]) and a significant reduction in the 65-80 group (adjusted HR, 0.74 [95% CI, 0.57–0.96]) with use >2 years. Adjusted for mortality, the NNT to reduce cardiovascular events in the ≥80 group and the 65-80 group were 48.8 and 68, respectively.