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Carotid Stenting vs. Endarterectomy: Vascular Anatomy Predicts Stroke Risk

Hatim Attar, MD

Müller MD, Ahlhelm FJ, von Hessling A, Doig D, Nederkoorn PJ, Macdonald S, et al. Vascular Anatomy Predicts the Risk of Cerebral Ischemia in Patients Randomized to Carotid Stenting Versus Endarterectomy. Stroke. 2017

There has been a longstanding debate on management of patients with carotid disease. In the ICSS study, patients were randomly assigned to Carotid Artery Stent (CAS) vs. Carotid Endarterectomy (CEA). CAS was related to higher peri-procedural stroke risk, but both therapies were equally effective in long-term stroke prevention. This study is a post-hoc analysis on a sub group of the ICSS study, providing the first randomized trial on vascular anatomy as an independent procedural risk factor for stroke during CAS and CEA. Studies have been completed assessing vascular anatomy for procedural risks with CAS, but none have compared the risk between CAS and CEA, making this study unique and its results invaluable.

In the ICSS MRI subgroup, brain MRI was performed before and 1-3 days after CAS or CEA; primary outcome was new diffusion restricted lesions. Patients in this study underwent Contrast Enhanced Magnetic Resonance Angiography (CE- MRA) or Computed Tomographic Angiography (CTA) to define vascular anatomy. Vascular anatomy was objectified with measurable criteria. Aortic arches were divided into three types based on origins of supra aortic arteries, and angles between all large vessels were defined, as shown below in the images.

 The authors validated the inter-rater reliability on reading these anatomic parameters. Associations were made between the laterality, stenosis length and degree, plaque ulcerations and vasculature angles.

There were 184 patients with vessel imaging; 97 were assigned to CAS, 87 to CEA. Procedural cerebral ischemia was found in 49 of the CAS group (51%), with only 14 after CEA (16%). After correcting for age, only two factors were found to be statistically significant in the CAS group—aortic arch configuration type 2 and 3, and larger ICA angulation (≥ 60 degrees). 

Author Interview: Alexandros Rentzos, MD, and Pia Löwhagen Hendén, MD, PhD

Alexandros Rentzos, MD, and Pia Löwhagen Hendén, MD, PhD

Alexandros Rentzos, MD, and Pia Löwhagen Hendén, MD, PhD

A conversation with Alexandros Rentzos, MD, Diagnostic and Interventional Neuroradiology, Sahlgrenska University Hospital, and Pia Löwhagen Hendén, MD, PhD, Anesthesiology and Intensive Care department, Sahlgrenska University Hospital, about the role of anesthesia and conscious sedation for patients undergoing embolectomy for stroke.

Interviewed by José G. Merino, MD, Associate Professor of Neurology, University of Maryland School of Medicine.

They will be discussing the paper, “General Anesthesia Versus Conscious Sedation for Endovascular Treatment of Acute Ischemic Stroke: The AnStroke Trial (Anesthesia During Stroke),” published in the June 2017 issue of Stroke.

Dr. Merino: Could you please summarize the key findings of your study and put them in context of what was known on the topic?

Drs. Rentzos and Löwhagen: Since a number of retrospective studies showed that general anesthesia during endovascular stroke treatment was associated with poor neurological outcome, conscious sedation became the main method in most neurointerventional centers after 2010. However, the retrospective studies were limited by important selection bias, such as inclusion of posterior strokes (in some of the series) and, importantly, more severe stroke in patients treated under GA. Furthermore, most retrospective studies on anesthesia technique did not describe the anesthesia technique, nor the anesthetic management!

At our institute, we have used mainly general anesthesia since 1991 when we started with endovascular stroke treatment, and, in our experience, patients treated with GA did not have worse neurological outcome. That is why we started the randomized trial AnStroke in 2013. The results were presented in ESOC 2017 in Prague on May 18. In our trial, general anesthesia did not lead to worse neurological outcome compared to conscious sedation.

Higher Admission Heart Rate Associated with Death and Poor Functional Outcome in ICH

Alexander E. Merkler, MD

Qiu M, Sato S, Zheng D, Wang X, Carcel C, Hirakawa Y, et al. Admission Heart Rate Predicts Poor Outcomes in Acute Intracerebral Hemorrhage: The Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial Studies. Stroke. 2016

Intracerebral hemorrhage is a devastating disease with a one-month mortality of 40%. Larger ICH volume, older age, and hematoma expansion are some of the factors associated with both poor functional outcome and death. Admission heart rate (HR) has previously been shown to predict higher mortality in coronary artery disease and ischemic stroke, but its impact on patients with ICH is unknown. 


In this study, Drs. Qiu et al perform a post-hoc analysis on data from the INTERACT trials to evaluate the effect of admission heart rate on outcome in ICH. Clinical outcomes included mortality and functional outcome (mRS) at 90 days. Imaging outcome was hematoma growth on 24 hour CT. HR was divided into quartiles (<65, 65-74, 75-84, ≥85) and Cox logistic regression was used to account for possible confounders in the relationship between admission HR and the outcomes of interest.

Of 3185 patients with ICH, patients with higher admission HR had higher BP, more frequent intraventricular extension of hematoma, and were less likely enrolled in China; patients with lower admission HR were more likely older, more often were taking a beta-blocker or antithrombotic, and had larger hematomas that were less likely to be in a lobar location.  Overall, higher admission HR was associated with higher mortality (adjusted hazard ratio for HR ≥85 vs. <65: 1.5; CI, 1.07-2.11). In addition, higher admission HR was associated with worse functional outcome at 90 days (adjusted odds ratio 1.33; CI 1.08-1.63). There was no significant association between admission HR and hematoma expansion on 24 hour CT.

Similar to coronary artery disease and ischemic stroke, admission HR appears to be associated with increased mortality and poor functional outcomes in patients with ICH. As the authors suggest, perhaps higher admission HR is a marker of poor general health, dehydration, anemia, or a marker of cardiac disease, all of which are predictors of poor outcome after stroke. One major limitation is the lack of adjustment for heart rate variability, which has also been shown to be associated with poor outcomes after stroke.  

In conclusion, admission HR is associated with increased mortality and poor functional outcome in patients with ICH. 

Residual Arterial Stenosis after Endovascular Thrombectomy: a Relationship with in Situ Thrombo-occlusion and Reocclusion Rates

Mark R. Etherton, MD, PhD
The advent of efficacious endovascular thrombectomy (EVT) for ischemic stroke secondary to acute occlusion of proximal anterior circulation vessels has allowed for the characterization of occlusive lesions. Understanding the underlying pathology of these occlusive lesions could be informative for predicting the success of the endovascular intervention as well as prognostication of clinical outcomes.

In the present study, Hwang et al. characterized residual stenosis post EVT at the site of the arterial occlusive lesion in an Asian population with acute ischemic stroke secondary to middle cerebral artery M1 occlusion. In this population with a high prevalence of intracranial atherosclerotic disease (ICAD), the authors’ hypothesis was that residual stenosis, as defined by the Arterial Occlusive Lesion (AOL) scale, would be sequelae of in situ thrombo-occlusion (IST) with underlying ICAD. Angiographic imaging during EVT and follow up imaging (MR or CT angiography) 5 to 7 days post-procedure was performed to assess stenosis.
Out of 163 patients enrolled in the study, 74 patients (45.5%) had partial recanalization (AOL 2) on post-procedural angiography. Rates of favorable clinical outcomes at 3 months (defined as mRS of 2 or less) did not differ between the group with partial (AOL 2) versus complete recanalization (AOL 3). Forty patients (24.5%) in the study were determined to have IST as their stroke etiology, and all of these patients had residual stenosis present on the post-procedural angiogram (AOL 2). 27% of patients with partial recanalization compared to only 1.1% of patients with complete recanalization developed instant reocclusion during EVT. In addition, those patients with partial recanalization during EVT were more likely to have worse stenosis or occlusion (10.8% vs 1.1%) on follow-up imaging. On multivariable regression analysis, delayed reocclusion in patients with partial recanalization was predicted by excellent baseline collateral-flow (OR 8.477; 95%CI 1.169-61.464) and neurological worsening post-procedure (OR 10.388; 95%CI 1.287-83.876).

It is important to note that the authors used a radiologic-based approach to identify IST that was based on the presence and severity (>50%) of residual stenosis and the presence of ICAD. The majority of patients with IST determined using these criteria were classified as partial recanalization with residual stenosis exceeding 50% on follow-up angiography. This study suggests that IST is a common cause of large vessel occlusion in an Asian population and that residual stenosis is associated with increased risk of reocclusion and early neurologic deterioration. Going forward, work should include controlling for endovascular approach utilized and characterizing the pathologic correlates for radiographic-determined IST.

Results of the Japanese Primary Prevention Project

Neal S. Parikh, MD

In Stroke, Dr. Uchiyama and colleagues report on their investigation of aspirin for primary stroke prevention in an at-risk, elderly cohort in Japan.

The Japanese Primary Prevention Project was intended to investigate the utility of aspirin for primary prevention in an Asian population–a population thought to be at greater baseline risk of intracranial hemorrhage (ICH). In this paper, the authors present results of a post-hoc analysis regarding ischemic stroke, TIA and ICH.

The study was a nationwide, multicenter, randomized, open-label trial. Patients between the ages of 60-85 and with at least one vascular risk factor were recruited from 2005 to 2007 by primary care doctors. Patients with a prior vascular event and those with atrial fibrillation were excluded, as were those with bleeding disorders and those already on a different anti-platelet agent. Patients were randomized to 100 mg of aspirin or no aspirin.

The primary outcome was a composite of cardiovascular death, nonfatal stroke, and nonfatal MI. Ischemic stroke, ICH, TIA were among the secondary endpoints, of which ischemic stroke, TIA, and ICH are specifically discussed in this article.


Over 14,000 patients were followed for median of 5 years. The mean age was 70, and approximately 60% of patients were female. 85% of patients in both groups had hypertension, 72% had dyslipidemia, and 34% had diabetes. Self-reported adherence in the aspirin group at 5 years was 76%; adherence to the no aspirin assignment was 90%.

At 5 years, there was not a significant difference in the cumulative rate of any stroke or TIA: 2.068% in the aspirin group versus 2.299% in the no aspirin group; adjusted HR 0.927 (95% CI, 0.74-1.16). Similarly, there was not a significant difference in the individual outcomes of any stroke, ischemic stroke, and ICH. In Cox regression analysis, aspirin use was not significantly associated with cerebrovascular outcome rates.

The results are consistent with prior studies conducted in Western populations in which aspirin was not effective for stroke primary prevention. The key take home message may be the explanation of low outcome rates: aggressive risk factor management, particularly of hypertension.

Declining Rate of IV Heparin Use in Acute Ischemic Stroke in Korea

Jay Shah, MD

Chung J-W, Kim BJ, Han M-K, Ko Y, Lee S, Kang K, et al. Impact of Guidelines on Clinical Practice: Intravenous Heparin Use for Acute Ischemic Stroke. Stroke. 2016

IV heparin has been available since the 1940’s and its role in ischemic stroke has been constantly debated. IV heparin has a clear indication in cardiac ischemia and many presume its efficacy should translate in acute ischemic stroke as well. However, numerous studies have failed to show benefit and American Stroke Association does not recommend anticoagulation acutely. Because heparin has been available for numerous years, there is little information on contemporary use and this study evaluated recent IV heparin trends across 12 hospitals in Korea in a 5 year span from 2008-2013.


Data was obtained from an acute stroke registry that included consecutive stroke patients. Information regarding stroke characteristics, recanalization treatment and antithrombotic treatment during hospitalization and post-discharge were collected. In total, 23,425 patients were included in the study. In the study period, the rate of recanalization treatment increased. Use of IV heparin decreased consecutively during the study period with use of 4.3% in 2013 compared to 9.7% initially. In the small proportion of patients that were treated with IV heparin, atrial fibrillation was associated with more frequent use.

This study shows declining rates of IV heparin use in acute ischemic stroke. This coincides with a 2009 publication of a Korean stroke clinical practice guideline and supports adherence to guidelines by neurologist. Interestingly, atrial fibrillation was associated with use of IV heparin. Typically, cardioembolic strokes are generally larger and acute anticoagulation is not pursued due to hemorrhage risk. Furthermore, subsequent short-term stroke risk following a cardioembolic stroke is relatively lower (unlike large vessel disease) and delaying anticoagulation until hemorrhage risk is lower has become the standard practice. Use of IV heparin is sometimes reserved for patients with critical carotid stenosis awaiting carotid endarterectomy but such decisions are made on case-by-case basis. This study further affirms that clinical guideline recommendations impact clinical decision making and have the ability to impact outcomes as well.

Is Anticoagulation Safe in ENT/CNS Infection Associated Central Venous Thrombosis?

Alexander E. Merkler, MD


Head and Neck Infections are not uncommonly associated with central venous thrombosis (CVT). Previous studies claimed that in as many as 60% of cases of CVT, there is an associated ENT or CNS infection, although more recent publications state that the rates of associated infections are much less, likely due to improved antibiotic treatment. Despite the presence of intracerebral hemorrhage, CVT is typically treated with anticoagulation. On the other hand, there is insufficient evidence to support treatment with anticoagulation for CVT due to or associated with a concurrent head or neck infection.

In the current study, Dr. Zuurbier et al. assess the differences between CVT patients with and without concurrent head or neck infection. In addition, the authors assess the use and effect of anticoagulation in patients with CVT and concurrent infection. This study data was collected as part of the prospectively gathered International Study on Cerebral Venous and Dural Venous Thrombosis (ISCVT) which included 624 adults with CVT.

Out of the 624 patients with CVT, 77 patients had an infection. Twenty had an infection outside of the head or neck and were excluded. Thus, out of the 600 patients that remained, 57 patients had a head or neck infection, out of which an ENT infection (mastoiditis) was the most common. Thirteen (22.8%) had a CNS infection. As compared to patients without an infection, cavernous sinus thrombosis was more common in patients with an infection (7.7 versus 0.7%). In addition, an ICH at baseline was less common in patients with an infection (21.1 versus 41.6%). The proportion of patients who received therapeutic anticoagulation was the same in patients with or without an infection (82.% versus 83.7%). Of the patients with an infection, there were no significant baseline differences between those who received anticoagulation and those who did not.

Neurological outcomes (as defined by mRS upon last follow-up) were similar between patients with or without infections; 15.8 versus 13.7% of patients were dead or dependent (mRS>2) at last follow-up. In addition, mortality was similar between patients with and without infection (5.3% versus 3.3%). A new ICH was more common in patients with an infection than without an associated infection (12.3 versus 5.3%) and although not statistically significant due to low numbers of patients, clinical worsening was more frequent in patients with an infection who were treated with anticoagulation (31.9 versus 10%). On the other hand, despite clinical worsening, clinical outcomes at last follow-up and mortality were very similar in patients with an infection treated or not treated with anticoagulation.

One of the most surprising findings of this study was the fact that clinicians were not deterred in prescribing full dose anticoagulation in patients with active ENT/CNS infection. Although overall mortality and neurological outcomes were similar in patients with CVT and concurrent infections treated or not treated with anticoagulation, only 10 patients with CVT and concurrent infection were not treated with anticoagulation and therefore it is hard to attest to the efficacy/safety of anticoagulation in this particularly challenging subgroup of patients.

IV-tPA Treatment Prior to Mechanical Thrombectomy Did Not Improve Outcome in a Retrospective Matched Analysis

Jay Shah, MD

Broeg-Morvay A, Mordasini P, Bernasconi C, Bühlmann M, Pult F, Arnold M, et al. Direct Mechanical Intervention Versus Combined Intravenous and Mechanical Intervention in Large Artery Anterior Circulation Stroke: A Matched-Pairs Analysis. Stroke. 2016

Recently, 5 trials have consistently shown that mechanical thromectomy (MT) improves outcomes in acute ischemia due to proximal occlusion within the anterior circulation. In these trials, rates of intravenous tissue-type plasminogen activator (IV-tPA) were similar among treatment and medical arms thus raising the question whether pre-treatment with IV-tPA is necessary. In this study, the investigators compared clinical outcomes and safety of direct MT alone versus bridging IV-tPA.

This retrospective study is based on a stroke registry that registered stroke patients across a 5 year span. In total, 156 patients were treated with bridging tPA and 239 with direct MT. 40 patients within the latter group had no contraindications to IV-tPA but were opted for direct MT therapy. These patients were matched with patients receiving bridging therapy. Clinical outcomes at three months did not differ between groups; however, there was a trend toward better improvement in the direct MT group. While the rate of symptomatic hemorrhage did not differ, there was higher rates of asymptomatic hemorrhage in the bridging group. Lastly, recanalization and reperfusion rates were similar in both groups.

This study raises an interesting clinical question. Certainly, IV-tPA has been the standard of care for acute ischemic stroke patients. However, in the current new era of endovascular intervention, its role has been questioned in patients who qualify for MT. The majority of patients within the 5 randomized trials did receive IV-tPA per standard practice. Thus, guidelines have recommended to treat with IV-tPA if patients are eligible. tPA can usually be administered quicker and may aid in recanalization. However, recanalization rates of large vessel occlusions are poor and these patients will require MT. IV-tPA treatment in this group, as this study points out, does not improve clinical outcome and may increase rate of hemorrhage. This study was a retrospective study and the number of patients are relatively small. The reason for excluding IV-tPA to the 40 eligible patients is not clear and thus subject to selection bias. tPA may recanalize small vessels particularly within the penumbra and this may be important until recanalization of the proximal occluded artery can be achieved. From a practical standpoint, most hospitals are not endovascular-capable and thus need to transported to a comprehensive stroke center leading to an extensive time difference between tPA administration and MT. Therefore, IV-tPA use should follow current established guidelines. However, future prospective trials should address bridging IV-tPA in combination with MT.

By |April 8th, 2016|treatment|0 Comments

Intra-Arterial Therapy, Post-Treatment Infarct Volumes, and Functional Outcomes in the ESCAPE Trial

Peggy Nguyen, MD

Al-Ajlan FS, Goyal M, Demchuk AM, Minhas P, Sabiq F, Assis Z, et al. Intra-Arterial Therapy and Post-Treatment Infarct Volumes: Insights From the ESCAPE Randomized Controlled Trial. Stroke. 2016

Outcome measurements in stroke trials commonly use measurements such as the mRS, NIHSS, or Barthel index as surrogates of functional improvement; the primary outcome measurement in the ESCAPE trial was the commonly used 3-month mRS. However, the relationship between outcomes at the functional level versus outcomes at a radiologic or anatomical level are not always delineated. Here, the authors perform a post-hoc analysis of the ESCAPE trial data, to evaluate the effect of IAT on saving brain tissue, and secondarily analyzed (1) clinical and imaging variables at baseline associated with post treatment infarct volume as well (2) the relationship between post treatment infarct volume and the 3-month mRS.

In the ESCAPE trial, the median post treatment infarct volume in the IAT group was significantly
lower than the control group (15.5 mL vs 33.5 mL, p < 0.01). Similarly, regardless of the intervention, successful recanalization in both groups was associated with smaller infarct volumes (14.5 mL vs 35 mL, p < 0.01). Baseline variables that were independently associated with smaller post treatment infarct volume were baseline NIHSS, site of occlusion, baseline ASPECTS and recanalization status, while age, sex, treatment type, IV tPA and time from onset to randomization were not. Post treatment infarct volume was found to strongly predict the 3-month mRS, particularly when including the change from baseline NIHSS.

Some interesting points came out of this study. The results reinforce the finding that recanalization, regardless of intervention, is a significant predictor of smaller infarct volumes. Interestingly, age had no interaction with the infarct volumes; one of the current debates in the stroke world these days is the benefit of IAT in older populations and this finding seems to suggest that age might not be a criteria for intervention if other variables are equal. Thirdly, the association of post treatment infarct volume with 3-month mRS was strongest when modeled with the change in baseline NIHSS, which makes sense, given large strokes in silent areas do not necessarily lead to better (or worse) outcomes, and small strokes in eloquent areas may have small post-treatment infarct volumes, but poor functional outcomes. This last finding, in a roundabout way, reinforces the utility of functional measures, such as mRS or Barthel index as outcome measures for clinical trials, rather than anatomical or radiological markers. 
By |April 4th, 2016|treatment|0 Comments

Clear and Robust Benefit From Solitaire Stent Retriever in Acute Ischemic Stroke: Pooled Analysis From 4 Clinical Trials

Jay Shah, MD

Campbell BCV, Hill MD, Rubiera M, Menon BK, Demchuk A, Donnan GA, et al. Safety and Efficacy of Solitaire Stent Thrombectomy: Individual Patient Data Meta-Analysis of Randomized Trials. Stroke. 2016

The five positive endovascular trials in acute ischemic stroke have revolutionized the management of acute cerebral ischemia and established endovascular revascularization as standard of care in eligible patients. However, there were differences in device type and procedures in the trials. Thus, the authors of all trials agreed to pool patient data in order to potentially detect subgroup differences. In this study, data from 4 trials (SWIFT PRIME, ESCAPE, EXTEND-IA, and REVASCAT) were pooled to examine treatment effects in patients specifically treated with Solitaire stent retriever. The primary outcome was degree of disability at 90 days as evaluated by modified rankin scale (mRS). 

In total, 787 anterior circulation ischemic strokes were included and 401 were randomized to thrombectomy. The odds ratio for improvement in mRS was 2.7 with a number needed to treat of 2.5 patients to improve at least one level on the mRS. There was benefit in secondary outcomes as well such as early neurological recovery. These benefits were consistent across various patient characteristics such age, gender, stroke severity, site of occlusion, presence of tandem cervical carotid occlusion, ASPECT score, and time to randomization. 

There is clear benefit to endovascular intervention in patients with acute ischemic stroke. The benefit is likely a direct result of recanalization and reestablishing perfusion rather than a direct effect of the device itself. With increasing experience, the use of stent retrievers such as Solitaire will likely increase and patient selection will broaden. The subgroup analysis of this study suggests that patients >80 age showed benefit and age should not be sole exclusion criterion. Similarly, there was equal benefit in “low” stroke scale < 15 compared to >20 although decision to intervene on NIHSS < 6 should be made on an individual basis as the trials had very few patients within this category. Lastly, similar to IV-tPA, there is a declining probability of good outcome with time so once a treatment decision is made in an expedited but judicious manner, the focus should then tailor to minimizing delays. However, clinical utility in patients with low ASPECT scores and poor collaterals is unclear and should be addressed in future trials. 

By |March 31st, 2016|treatment|0 Comments