Dear Sir:
Recently, the large international observational Endovascular Treatment for Isolated Cervical Internal Carotid Artery Occlusion (ETIICA) study investigated the safety and efficacy of acute endovascular therapy (EVT) in patients with acute ischemic stroke and isolated cervical internal carotid artery occlusion (c-ICA-O) [1]. Three-month functional outcomes after EVT were similar to those in patients receiving best medical treatment (BMT) alone [1]. As other registries report similar findings, a randomized controlled trial seems warranted [2]. However, safety concerns in a subset of patients remain, as an increased risk of symptomatic intracranial hemorrhage (ICH) was observed in the EVT group of ETIICA compared with those receiving BMT alone (8 [1.6%] vs. 0 [0.0%]) [1]. This raises the question of the potential risk of EVT in patients with an increased risk of ICH, such as those taking oral anticoagulation (OAC) at the time of stroke.
Studies in patients undergoing EVT due to intracranial largevessel occlusion stroke have reported that prior OAC intake does not place patients at a higher risk of ICH, especially if taking a direct oral anticoagulant (DOAC) [3,4]. However, whether this holds true for patients with isolated c-ICA-O remains unknown [5].
Therefore, we aimed to evaluate the effect of OAC intake before the index stroke on the safety and efficacy of EVT in patients with isolated c-ICA-O.
Details of the ETIICA study have been published [1]. In short, the registry included patients with ischemic stroke and isolated c-ICA-Os presenting within 24 hours from the last-seen-well. This study compared BMT alone with BMT plus EVT. ETIICA included patients treated between 2018 and 2022 at 42 sites in Europe and North America. This subgroup analysis compared patients with ETIICA who underwent EVT and were on pre-stroke OAC (vitamin K antagonists or DOACs) with those who underwent EVT and were not on OAC. Patients who received bridging intravenous thrombolysis (IVT) were excluded because IVT is a confounder of ICH. Outcomes of interest were symptomatic ICH (defined as parenchymal hematoma type 2 [PH2] with an increase of at least four points on the National Institutes of Health Stroke Scale [NIHSS] score) or any hemorrhage at 24-36 hours postintervention, as well as ordinal 3-month modified Rankin Scale (mRS) scores (shift) [6].
Continuous variables are presented as mean with standard deviation and median with interquartile range, depending on the data distribution. Categorical variables are presented as absolute numbers and percentages. The baseline characteristics of patients with and without prior OAC use were compared using the chi-square test for categorical variables and either the independent t-test or the Mann-Whitney U test for continuous variables, as appropriate.
Shift analysis was performed for the 3-month mRS scores. Binary logistic regression analysis was performed for both ICH and symptomatic ICH. To adjust for potential confounding factors, we applied normalized Inverse Probability of Treatment Weighting based on a propensity score estimated using logistic regression. The model included the following predefined covariates: age, sex, pre-mRS score, NIHSS score at admission, atrial fibrillation, heart failure, arterial hypertension, current or recent smoking, previous stroke or transient ischemic attack, atherosclerosis, cardioembolism, dissection, antiplatelet use, and carotid artery stenting. Age and NIHSS score were modelled as restricted cubic splines with three knots. Statistical testing was done within an exploratory framework at a two-sided significance level of α=0.05. Statistical analyses were performed using Stata MP/18 (StataCorp. 2023, College Station, TX, USA).
A total of 285 of the 998 (28.6%) patients with ETIICA were eligible for this analysis (exclusions: 511 patients did not undergo EVT and 202 patients underwent bridging thrombolysis), of whom 64 patients had prior OAC. Table 1 presents the patient characteristics, including risk factors, stroke etiology, and clinical status at admission and during treatment.
Notably, even though there was a numerical difference in PH2 between patients with and without prior OAC (2 [3.2%] vs. 2 [0.9%]), no difference in occurrence risk of any ICH (9/63 [14.3%] vs. 29/220 [13.2%]; adjusted odds ratio, aOR, 1.31 [95% confidence interval, CI, 0.39-4.44]) or symptomatic ICH (2/63 [3.2%] vs. 3/220 [1.4%]; aOR, 1.26 [95% CI, 0.19-8.51]) (Figure 1 for details) was observed. This was also true in the crude, unadjusted analysis (data not shown). Furthermore, the mRS-defined functional outcome at 3 months was similar between patients with and without OAC use before EVT (aOR, 1.00 [95% CI, 0.35- 2.90]).
To date, the optimal care for isolated c-ICA-O remains unknown, with the safety and efficacy of acute revascularization measures being in question [2,7-9]. The ETIICA registry, the largest international registry collecting observational data of this patient population, has enabled a detailed assessment of individual treatment aspects [1]. Our subgroup analysis adds data to the safety of EVT in patients with acute stroke and isolated c-ICA-O [1]. Although ETIICA found higher rates of ICH in patients undergoing EVT compared with BMT alone, this increased risk of ICH did not stem from prior OAC use.
Our results support the notion that prior OAC use does not increase the risk of adverse bleeding outcomes in stroke patients with c-ICA-O undergoing EVT (Figure 1). This is reassuring, as approximately 1 in 7 patients with isolated c-ICA-O presented with OAC, indicating that c-ICA-O is not exclusively caused by atherosclerosis or dissection but by comorbidities requiring OAC [1]. As the call for randomized controlled clinical trials in this patient population continues, observational data defining patient characteristics that may or may not be recruited safely into such trials in the future are crucial. Although acknowledging the retrospective data collection, selection bias, lack of central reading, unblinded outcome assessment, and the missing data on OAC type (i.e., vitamin K antagonists, DOACs) and compliance, we contend that prior OAC should not be an exclusion criterion when designing a future treatment trial.
PDF Links
PubReader
ePub Link
XML Download
Full text via DOI
Download Citation
Print
