prevention

Victor J. Del Brutto, MD

Ntaios G, Pearce LA, Meseguer E, Endres M, Amarenco P, Ozturk S, et al. Aortic Arch Atherosclerosis in Patients With Embolic Stroke of Undetermined Source: An Exploratory Analysis of the NAVIGATE ESUS Trial. Stroke. 2019

When it comes to establishing the mechanism of injury in a stroke victim, the label “unknown/undetermined” deprives the patient of receiving the appropriate prognosis and strategy for secondary prevention. One-fourth of ischemic strokes are identified as cryptogenic without a definite understanding of the cause, and a sizable proportion of them will fit into the concept of embolic stroke of undetermined source (ESUS). The cause of ESUS could be an under-recognized cardiac source or a non-stenosing arterial lesion. Despite seminal studies in the 1990s that have identified a causal association between protruding plaques in the aortic arch and ischemic stroke, aortic arch atherosclerosis (AAA) is often overlooked during routine stroke work-up, thus falling into the category of stroke of undetermined etiology.

The current manuscript published by Ntaios and colleagues reports the exploratory analysis of the subgroup of individuals who participated in the New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source (NAVIGATE-ESUS) trial and underwent transesophageal echocardiogram (TEE) for evaluation of AAA. The authors found a prevalence of 19% of AAA among patients with ESUS, from which one-third (8% of the total cohort) were considered to have high-risk complex plaques as defined by the presence of ulceration, thickness greater than 4 mm, or presence of a mobile thrombus. As noticed by the authors, the prevalence of AAA might be underestimated due to lower atherosclerotic risk factors in those who underwent TEE. Increasing age, diabetes mellitus and aortic valve disease, as well as geographic region (east Asia and eastern Europe), were significant determinants of AAA in the multivariable analysis. In addition, chronic infarcts and multi-territorial infarcts were associated with AAA, arguing against the common belief that multifocal strokes are exclusively cardioembolic. There was a non-significant trend for higher rate of stroke recurrence in patients with complex AAA (7.2% annualized rate) when compared to those without AAA (5.6% annualized rate). Data from this analysis was merged with two other randomized controlled trials to construct a meta-analysis of anticoagulation versus antiplatelet therapy in patients with cryptogenic stroke and AAA. The meta-analysis found no significant difference in the rate of stroke recurrence between the two antithrombotic approaches.

Yan Hou, MD, PhD

Paciaroni M, Agnelli G, Caso V, Silvestrelli G, Seiffge DJ, Engelter S, et al. Causes and Risk Factors of Cerebral Ischemic Events in Patients With Atrial Fibrillation Treated With Non–Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention: The RENo Study. Stroke. 2019;50:2168–2174

Non–vitamin K antagonist oral anticoagulants (NOACs) are currently recommended as the stroke prevention for patients with nonvalvular atrial fibrillation (AF). Despite compliance with NOAC, patients with nonvalvular AF may still experience ischemic cerebrovascular events. The RENO study is a multicenter case-control study to identify the etiology and risk factors for ischemic events occurring during NOACs (dabigatran, apixaban, rivaroxaban, or edoxaban) therapy in patients with nonvalvular AF.

The study included 713 cases (641 ischemic strokes and 72 TIA) and 700 controls (patients did not experience cerebrovascular events). Cases who did not guarantee compliance or who had suspended NOAC at least 24 hours before the cerebrovascular event were excluded. Most strokes (64%) occurring during NOACs therapy were caused by cardioembolism, but about 30% of strokes were found due to non-cardioembolic etiology. Among the risk factors (age, sex, hypertension, diabetes mellitus, current cigarette smoking, hyperlipidemia, ischemic heart disease, peripheral artery disease, alcohol abuse, obesity, previous stroke/transient ischemic attack, creatinine clearance, duration of NOAC treatment, doses of NOACs, AF classification, CHA₂DS₂-VASc score, left atrial enlargement on echo), off-label low doses of NOACs (OR, 3.18), atrial enlargement (OR, 6.64), hyperlipidemia (OR, 2.40), and high CHA₂DS₂-VASc score (OR, 1.72 for each point increase) were associated with ischemic events. The reasons for prescribing low doses of NOAC included fear of bleeding, history of bleeding, concomitant antiplatelet therapy, recurrent falls, amyloid angiopathy, anemia, history of cancer, age, gastrointestinal discomfort, and hypertension or other causes. Low clearance of creatinine (OR, 0.98 for 1 mL/min increase) and high CHA₂DS₂-VASc score (OR, 1.35 for each point increase) were also found associated with prescription of low-dose NOACs.   

Alan C. Cameron, MB ChB, BSc (Hons), MRCP

Rahman H, Khan SU, Nasir F, Hammad T, Meyer MA, Kaluski E. Optimal Duration of Aspirin Plus Clopidogrel After Ischemic Stroke or Transient Ischemic Attack: A Systematic Review and Meta-Analysis. Stroke. 2019;50:947–953.

Through a systemic review and meta-analysis of 10 randomised trials comparing dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel versus aspirin alone in over 15,000 patients with ischaemic stroke (IS) or transient ischaemic attack (TIA), Rahman and colleagues demonstrate that £1 month of DAPT reduces the relative risk of recurrent IS by almost 50% with no increase in major bleeding. In contrast, £3 months of DAPT reduces IS by 28% but increases major bleeding, whilst >3 months of DAPT does not reduce recurrent IS and increases major bleeding. The reduction in risk of recurrent IS with £3 months of DAPT may be due to substantial early benefit within the first few days or weeks. The POINT and CHANCE trials suggest maximum benefit is achieved when DAPT is initiated within the first 24 hours after minor IS or high-risk TIA, which highlights a need for services that allow patients to be reviewed within this timeframe.

The risk of bleeding was greater in aspirin naïve patients in analysis of the EXPRESS and FASTER studies, highlighting a need to screen carefully for bleeding risk factors in this group of patients. Better blood pressure control combined with screening and management of bleeding risk factors is essential to ensure benefits from antiplatelet therapy are not offset by increased bleeding. Overall, we can be confident that DAPT is most effective and safe in the early weeks after minor IS or high-risk TIA to reduce the risk of recurrence.

Mohammad Anadani, MD

Ijäs P, Aro E, Eriksson H, Vikatmaa P, Soinne L, Venermo M. Prior Intravenous Stroke Thrombolysis Does Not Increase Complications of Carotid Endarterectomy. Stroke. 2018

The benefit of carotid endarterectomy (CEA) for symptomatic carotid stenosis is well established; however, the optimal timing of procedure after stroke is still a matter of debate. Although few studies showed an increased risk of periprocedural stroke and death with early CEA (within 48 hours), others did not. In patients who receive intravenous thrombolysis (IVT), CEA is often delayed due to a concern of increased risk of intracerebral hemorrhage (ICH). However, this delay may result in a theoretical increase in risk of recurrent stroke while waiting for CEA.

In this study, Ijäs and colleagues underwent a retrospective registry study to investigate the safety and optimal timing of CEA after IV thrombolysis (IVT).