Background:
The aim of this study was to determine the effect of smoking status on subsequent stroke risk in patients with minor ischemic stroke or TIA and to determine whether smoking modifies the ...effect of clopidogrel-based DAPT on subsequent stroke risk.
Methods:
This was a post-hoc analysis of the Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, which had a 90-day follow-up period. We used multivariable Cox regression and subgroup interaction analysis to determine the effect of smoking on the risk of subsequent ischemic stroke and major hemorrhage, respectively.
Results:
Data from 4877 participants enrolled in the POINT trial were analyzed. Among these, 1004 were current smokers and 3873 were non-smokers at the time of index event. Smoking was associated with a non-significant trend toward an increased risk of subsequent ischemic stroke during follow up (adjusted HR, 1.31 (95% CI, 0.97–1.78), p = 0.076). The effect of clopidogrel on ischemic stroke did not differ between non-smokers (HR, 0.74 (95% CI, 0.56–0.98), p = 0.03) and smokers (HR, 0.63 (95% CI, 0.37–1.05), p = 0.078), p for interaction = 0.572. Similarly, the effect of clopidogrel on major hemorrhage did not differ between non-smokers (hazard ratio, 1.67 (95% CI, 0.40–7.00), p = 0.481) and smokers (HR, 2.59 (95% CI, 1.08–6.21), p = 0.032), p for interaction = 0.613.
Conclusions:
In this post-hoc analysis of the POINT trial we found that the effect of clopidogrel on reducing subsequent ischemic stroke as well as risk of major hemorrhage did not depend on smoking status, indicating that smokers benefit to a similar degree from DAPT as non-smokers.
Background: It is unknown if race/ethnicity modifies the response to blood pressure (BP) lowering treatment after intracerebral hemorrhage (ICH). We aimed to examine the race/ethnicity differences in ...the response to BP lowering treatment after ICH. Methods: This is a post hoc analysis of the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2) trial. The primary outcome is good outcome, defined as 90-day modified Rankin Scale 0–3. The primary predictor is race/ethnicity for which we included non-Hispanic categories of White, Black, Asian, and the category of Hispanic. We fit adjusted logistic regression models with the predictor of race/ethnicity and models with the interaction term of treatment*race/ethnicity. Results: We included a total of 953 patients in our analysis (White = 213, Black = 112, Asian = 554, and Hispanic = 74). In the models with the interaction between race/ethnicity and treatment, we found that White patients assigned to the intensive treatment arm had lower predicted probability of good outcome than those assigned to the standard treatment arm (Model 1: 56.2% vs. 68.1%, p = .027; Model 2: 53.4% vs. 68.3%, p = .009). When divided into White and non-White groups, intensive treatment was associated with higher odds of serious adverse events in White group but not in the non-White group. In addition, there was an association between intensive treatment and higher risk of hematoma expansion in White patients and lower risk of hematoma expansion in non-White patients. Conclusions: In the ATACH-2, there was an interaction between race/ethnicity and response to BP lowering treatment after ICH, with White patients having an association between intensive blood pressure reduction and worse outcome.
Abstract only Introduction: Six patients have been described in the published literature with a clinical and radiographic presentation consistent with posterior reversible encephalopathy syndrome ...(PRES), but who also had extensive spinal cord lesions on MRI. We add two additional cases and after analyzing all eight cases have discovered characteristic patterns. In light of the already wide definition of PRES, we propose a new syndrome named hypertensive reversible encephalomyelitis syndrome or HyRES. Methods: We searched the Medline database using the terms “spinal PRES” and “spinal hypertensive encephalopathy,” which led to the identification of four case reports, that referenced another two cases. We analyzed these six cases in addition to our two cases. Results: Average age was 31 with five male and three female. All patients had severe acute hypertension and a longitudinally extensive myelitis with a confluent, expansive central cord T2 hyperintensity greater than 4 spinal segments in length, always involving the cervical spine. (see Figure 1) Almost all patients had hypertensive retinopathy (7/8), a favorable clinical course with only antihypertensive treatment (7/8), and resolution of the spinal cord lesions on follow-up imaging (7/8). Half of the patients had symptoms referable to the spinal cord lesions. Many of the features that are commonly seen in classic PRES were not present, such as seizure (0/8). Conclusion: HyRES shares clinical, radiographic, and, presumably, pathophysiologic attributes with PRES, but is a unique and consistent entity. Clinicians should suspect HyRES when patients with PRES have neurologic signs referable to the spinal cord or MRI lesions that extend to the cervicomedullary junction. It is important that clinicians and radiologists identify HyRES when they are considering, working up, or treating other causes of longitudinally extensive myelitis, which can have significant morbidity.
Abstract only Background: Cervical artery dissection (CAD) is a frequent cause of ischemic stroke and pseudoaneurysm (PA) formation is a common complication. There is limited literature on the risk ...factors for PA formation. In particular, the influence of specific medical therapy for CAD_antiplatelet versus anticoagulation_is unknown. We hypothesized that anticoagulation in the treatment of CAD is a risk factor for PA formation. Methods: We retrospectively reviewed 250 cases of CAD admitted to a single hospital between 2011 and 2014. A neuroradiologist diagnosed CAD and PA by CTA. We reviewed patient charts for several risk factors: antithrombotic therapy, associated trauma, subsequent stroke, and age. Outcome (resolution or growth at 3 months) and largest size (at any point in time) of PA was recorded. Statistics were non-parametric. Results: 35 patients had a diagnosis of CAD, PA, and follow-up vascular imaging at 3 months after onset. 27 patients presented concomitantly with CAD and PA; 8 patients later developed PA. Median patient age was 48 years, median PA length along longest axis was 8mm, 84% were treated with antiplatelets and 16% were treated with therapeutic anticoagulation. All patients treated with anticoagulation experienced PA growth versus 44% of those treated with antiplatelet agents (Fisher’s Exact p = 0.046). Younger age was also associated with PA growth (Wilcoxon rank sum test p = 0.0198) and there was a trend towards larger median pseudoaneurysm size in patients receiving anticoagulation (median size 17mm versus 5mm, p=0.09). Traumatic dissection and ischemic stroke were not associated with pseudoaneurysm development or size. Discussion: Our study finds that in the setting of CAD, treatment with anticoagulation and younger age are risk factors for PA growth; furthermore, patients on anticoagulation tend to have larger PAs. While the natural history of PAs is typically benign, many patients undergo invasive treatments and face the fear of other complications. Given the clinical equipoise surrounding CAD treatment, our findings may have important implications for patient care and should be replicated in a larger dataset.
IntroductionIncreased blood pressure variability (BPV) is detrimental after acute ischaemic stroke, but the interaction between BPV and neuroimaging factors that directly influence stroke outcome has ...not been explored.MethodsWe retrospectively reviewed inpatients from 2007 to 2014 with acute anterior circulation ischaemic stroke, CT perfusion and angiography at hospital admission, and a modified Rankin Scale (mRS) 30–365 days after stroke onset. BPV indices included SD, coefficient of variation and successive variation of the systolic blood pressure between 0 and 120 hours after admission. Ordinal logistic regression models were fitted to mRS with predictor variables of BPV indices. Models were further stratified by CT perfusion volumetric measurements, proximal vessel occlusion and collateral score.Results110 patients met the inclusion criteria. The likelihood of a 1-point rise in the mRS increased with every 10 mm Hg increase in BPV (OR for the 3 BPV indices ranged from 2.27 to 5.54), which was more pronounced in patients with larger ischaemic core volumes (OR 8.37 to 18.0) and larger hypoperfused volumes (OR 6.02 to 15.4). This association also held true for patients with larger mismatch volume, proximal vessel occlusion and good collateral vessels.ConclusionsThese results indicate that increased BPV is associated with worse neurological outcome after stroke, particularly in patients with a large lesion core volume, concurrent viable ischaemic penumbra, proximal vessel occlusion and good collaterals. This subset of patients, who are often not candidates for or fail acute stroke therapies such as intravenous tissue plasminogen activator or endovascular thrombectomy, may benefit from interventions aimed at reducing BPV.
Abstract only Background: In late 2015, we assembled a multi-disciplinary team to analyze current emergency department (ED) processes and identify improvement opportunities in the current “brain ...attack” (BA) protocol. Using lean process engineering tools, including time study analysis, gemba walks, and cause and effect diagrams, we mapped our baseline state and identified delaying activities that did not add value to the BA process. We defined a new BA process (see Figure 1) to eliminate waste and improve team communication, including 3 Time Outs to ensure that increased speed didn’t decrease safety. Methods: To determine the effect of our intervention, we retrospectively reviewed patients who were admitted to our ED as a BA for evaluation of possible acute ischemic stroke and had a CT brain after ED arrival between April 2015 and August 2016. ED arrival was defined as the time that patients physically arrived at the ED and “time to CT” was the time from ED arrival to the first time stamp of the CT brain. The time from ED arrival to tPA bolus was also measured for "door to needle" time. The time to CT and door to needle times were compared between BA patients before and after lean process improvements using Student’s T-test. Results: Our cohort included 239 patients who presented to the ED as a BA. We included 116 BA patients from before the intervention and 123 from afterwards. The mean±SD time to CT prior to the intervention was 19.0±13.9 minutes. After our lean process improvements the time to CT was 14.2±15.6 minutes. The delta of 4.8 minutes resulted in a significant reduction in time to CT, p = 0.012. There were 14 patients who received tPA prior to the intervention and 9 afterwards, for a total of 23 door to needle times (10% of cohort). Door to needle time was significantly shortened post-intervention (46±13 minutes versus 32±12 minutes, p=0.013). Conclusions: Lean process improvement methodology significantly reduces door to CT and door to needle times, supporting current AHA Target: Stroke goals and allowing faster treatment of patients with acute ischemic stroke. Incorporating time-outs into standardized processes that aim to deliver care more quickly may improve patient safety without substantially slowing down DTN times. Further investigation is required to determine whether the new process improved safety and clinical outcomes.
Elevated systolic blood pressure (SBP) after acute ischemic stroke and transient ischemic attack (TIA) is associated with future stroke risk.
To explore the association of dual antiplatelet therapy ...(DAPT) with stroke recurrence among patients with acute ischemic stroke and TIA with or without elevated baseline SBP.
This cohort study performed a post hoc subgroup analysis of the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, which was a multicenter trial conducted from 2010 to 2018 at 269 sites in 10 countries in North America, Europe, Australia, and New Zealand. Patients enrolled in POINT with available blood pressure and outcome data were included in this cohort. Statistical analysis was performed from November 2020 to January 2021.
Baseline SBP less than 140 mm Hg vs greater than or equal to 140 mm Hg and the interaction term of SBP (<140 mm Hg vs ≥140 mm Hg) × treatment group (aspirin vs DAPT).
The primary outcome was ischemic stroke during 90 days of follow-up. The statistical analysis fit Cox proportional hazards models adjusted for patient age, race, premorbid hypertension, diabetes, and final diagnosis of the qualifying event (stroke vs TIA).
Among 4781 patients in the cohort, the mean (SD) age was 64.6 (13.1) years; 2142 (44.8%) were male individuals, 3487 (72.9%) were White individuals, and 266 (5.6%) had a primary outcome of ischemic stroke during follow-up. There were 946 patients (19.8%) with baseline SBP less than 140 mm Hg and 3835 (80.2%) with SBP greater than or equal to 140 mm Hg. The interaction term (SBP × treatment) was significant (P for interaction = .03). In the subgroup of patients with SBP less than 140 mm Hg, the hazard ratio (HR) of DAPT vs aspirin alone for ischemic stroke was 0.36 (95% CI, 0.18-0.72; P = .004), whereas the HR in the subgroup with SBP greater than or equal to 140 mm Hg was 0.79 (95% CI, 0.60-1.02; P = .08). When evaluating the outcome of ischemic stroke within 7 days of randomization, the interaction term was significant (P for interaction = .02), and the HR for patients with DAPT with SBP less than 140 mm Hg was 0.19 (95% CI, 0.07-0.55; P = .002).
In the POINT trial, patients with SBP less than 140 mm Hg at presentation received a greater benefit from 90 days of DAPT than those with higher baseline SBP, particularly for reduction of early ischemic stroke recurrence. Additional research is needed to replicate these findings and potentially test whether mild SBP reduction and DAPT within 12 hours of stroke onset lowers early risk of stroke recurrence.
Intracerebral hemorrhage (ICH) is a serious complication of brain arteriovenous malformation (AVM). Apolipoprotein E (APOE) ε4 is a well-known genetic risk factor for ICH among persons without AVM, ...and cerebral amyloid angiopathy is a vasculopathy frequently observed in APOE ε4 carriers that may increase the risk of ICH.
To assess whether APOE ε4 is associated with a higher risk of ICH in patients with a known AVM.
This cross-sectional study including 412 participants was conducted in 2 stages (discovery and replication) using individual-level data from the UK Biobank (released March 2012 and last updated October 2023) and the All of Us Research Program (commenced on May 6, 2018, with its latest update provided in October 2023). The occurrence of AVM and ICH was ascertained at the time of enrollment using validated International Classification of Diseases, Ninth Revision and Tenth Revision, codes. Genotypic data on the APOE variants rs429358 and rs7412 were used to ascertain the ε status.
For each study, the association between APOE ε4 variants and ICH risk was assessed among patients with a known AVM by using multivariable logistic regression.
The discovery phase included 253 UK Biobank participants with known AVM (mean SD age, 56.6 8.0 years, 119 47.0% female), of whom 63 (24.9%) sustained an ICH. In the multivariable analysis of 240 participants of European ancestry, APOE ε4 was associated with a higher risk of ICH (odds ratio, 4.58; 95% CI, 2.13-10.34; P < .001). The replication phase included 159 participants with known AVM enrolled in All of Us (mean SD age, 57.1 15.9 years; 106 66.7% female), of whom 29 (18.2%) sustained an ICH. In multivariable analysis of 101 participants of European ancestry, APOE ε4 was associated with higher risk of ICH (odds ratio, 4.52; 95% CI, 1.18-19.38; P = .03).
The results of this cross-sectional study of patients from the UK Biobank and All of Us suggest that information on APOE ε4 status may help identify patients with brain AVM who are at particularly high risk of ICH and that cerebral amyloid angiopathy should be evaluated as a possible mediating mechanism of the observed association.
The number of mechanical thrombectomy (MT) passes is strongly associated with angiographic reperfusion as well as clinical outcomes in patients with anterior circulation ischemic stroke. However, ...these associations have not been analyzed in patients with basilar artery occlusion (BAO). We investigated the influence of the number of MT passes on the degree of reperfusion and clinical outcomes, and compared outcome after ≤3 passes versus >3 passes.
We used data from the prospective multicentric Endovascular Treatment in Ischemic Stroke (ETIS) Registry at 18 sites in France. Patients with BAO treated with MT were included. The primary outcome was a favorable outcome, defined as a modified Rankin Scale score of 0-3 at 90 days. We fit mixed multiple regression models, with center as a random effect.
We included 275 patients. Successful recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) 2b-3) was achieved in 88.4%, and 41.8% had a favorable outcome. The odds ratio for favorable outcome with each pass above 1 was 0.41 (95% CI 0.23 to 0.73) and for recanalization (mTICI 2b-3) it was 0.70 (95% CI 0.57 to 0.87). In patients with ≤3 passes, the rate of favorable outcome in recanalized versus non-recanalized patients was 50.5% versus 10.0% (p=0.001), while in those with >3 passes it was 16.7% versus 15.2% (p=0.901).
We found that BAO patients had a significant relationship between the number of MT passes and both recanalization and favorable functional outcome. We further found that the benefit of recanalization in BAO patients was significant only when recanalization was achieved within three passes, encouraging at least three passes before stopping the procedure.
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