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Direct Oral Anticoagulants Versus Warfarin in Cancer Patients with Atrial Fibrillation

Mona Al Banna, MB BCh, MSc

Chan YH, Chao TF, Lee HF, Chen SW, Li PR, Liu JR, et al. Clinical Outcomes in Atrial Fibrillation Patients With a History of Cancer Treated With Non-Vitamin K Antagonist Oral Anticoagulants: A Nationwide Cohort Study. Stroke. 2021.

Atrial fibrillation is a known risk factor for stroke, increasing stroke risk 5-fold and mortality 2-fold compared to patients without atrial fibrillation. Cancer causing a hypercoagulable state is another well-known risk factor for stroke. Current guidelines recommend direct oral anticoagulants (DOACs) in patients with non-valvular atrial fibrillation. In patients with cancer who develop atrial fibrillation, warfarin or low-molecular weight heparin have traditionally been preferred over the direct oral anticoagulants.

In this study, Chan et al. investigated the effectiveness and safety of the DOACs when compared to warfarin in this population. A nationwide retrospective cohort study was performed using the Taiwan National Health Insurance Research Database. They identified 85,641 patients diagnosed with atrial fibrillation and treated with an anticoagulation over a 5-year period. Of those AF patients with a diagnosis of cancer, 6274 were treated with DOACs and 1681 were treated with warfarin. The DOAC group had a lower risk of ischemic stroke, acute myocardial infarction, major adverse limb events and venous thrombosis compared to the warfarin group. DOAC use was associated with a lower risk of ICH and major bleeding when compared to warfarin. Subgroup analysis was also performed to determine how different DOACs or different dosages of DOACs compared to warfarin. In general, there was lower risk of thrombotic events and major bleeding for DOACs over warfarin irrespective of DOAC type and whether it was standard-dose or low-dose. In addition, this benefit of DOACs over warfarin was consistent across patients with different types of cancer and at different stages of disease activity.

By |September 24th, 2021|clinical, treatment|0 Comments

Article Commentary: “Fluid-Attenuated Inversion Recovery May Serve As a Tissue Clock in Patients Treated With Endovascular Thrombectomy”

Parth Upadhyaya, DO

Aoki J, Sakamoto Y, Suzuki K, Nishi Y, Kutsuna A, Takei Y, et al. Fluid-Attenuated Inversion Recovery May Serve As a Tissue Clock in Patients Treated With Endovascular Thrombectomy. Stroke. 2021;52:2232–2240.

Based on WAKE-UP (2018), THAWS (2020), and smaller single-center trails, the concept of FLAIR signal change as a surrogate timekeeper in hyperacute stroke has shown both safety and efficacy for intravenous thrombolysis. Now, in the age of extended window endovascular thrombectomy (EVT), predictors of good clinical outcome beyond time, age and medical risk factors become prudent for patient selection. In this study, Aoki et al. hypothesize if FLAIR signal change can predict clinical outcome after EVT.

From a prospective registry of 324 consecutive EVT patients presenting with acute ischemic stroke, 227 were retrospectively enrolled from September 2014 to December 2018. Those with premorbid mRS score 0 to 1 with available FLAIR imaging were included; patients with contraindications to MRI were excluded. FLAIR positivity was defined by new hyper-intense signal at DWI-positive lesion site; subtle changes were measured using contralateral signal intensity ratio of 1.2. The median age of patients was 74, NIHSS 15, and symptoms onset to imaging 155 minutes. Ischemic core volume and NIHSS were not significantly different in timing to FLAIR imaging from less than 2 hours to greater than 12 hours. 

By |September 10th, 2021|clinical, treatment|0 Comments

ESOC 2021 Session: “Non-Reperfusion Therapies for Acute Ischemic Stroke Treatment: Something New in the Pipeline?”

Karissa Arthur, MD

European Stroke Organisation Conference
September 1–3, 2021

Dual Antiplatelet Therapy for Minor Acute Ischemic Stroke: Clopidogrel vs Ticagrelor: Pierre Amarenco, Paris University

In this session, Dr. Amarenco compared clopidogrel versus ticagrelor for minor acute ischemic stroke. He first summarized data for aspirin monotherapy showing that it reduces the risk of ischemic stroke by 60%, and the 6-week risk of disabling stroke by 70%. He then called to attention the CHANCE and POINT trials, as well as a pooled analysis of both, showing that dual antiplatelet therapy with aspirin plus clopidogrel after a minor stroke or TIA is 34% superior to aspirin alone in preventing stroke in the first 21 days. Dr. Amarenco went on to discuss the shortcomings of clopidogrel, with specific regard to CYP2C19 loss of function carriers in which there is less efficacy for stroke prevention. In contrast to clopidogrel, ticagrelor is a direct acting drug which does not require biotransformation, binds reversibly to platelets, has faster onset, higher platelet inhibition, and faster offset and therefore has a more attractive profile than clopidogrel. 

ESOC 2021 Session: “Scientific Communication 06 – Acute Treatment and Thrombolysis”

Vignan Yogendrakumar, MD, MSc
@VYogendrakumar

European Stroke Organisation Conference
September 1–3, 2021

This session opened with a presentation by Dr. Mikhail Kalinin and the CEREHETIS Investigators on the potential neuroprotective effect of Cerebrolysin as an add-on therapy during acute reperfusion. In a pilot RCT designed to assess safety, patients were randomized to cerebrolysin + IV tPA versus IV tPA alone. The primary outcome of the study was post-treatment symptomatic hemorrhagic transformation. 117 patients were randomized to the intervention arm, while 201 were randomized to the control arm.  Symptomatic hemorrhagic transformation occurred at lower rates in those who received cerebrolysin + thrombolysis, compared to thrombolysis alone. However, functional outcomes (mRS ≤ 2) did not differ between the two groups.

This was followed by a presentation by Dr. Wayneho Kan and the American Heart Association Get With The Guidelines-Stroke group. Using the registry of 160,000+ patients, Dr. Kan presented on the outcomes of tPA use in patients who were on a NOAC versus those not on anticoagulation using propensity score overlap weighting and regression modelling. Adjusting for baseline clinical factors, the risks of symptomatic intracranial hemorrhage did not differ between the two groups (sICH: aOR, 0.88 [95%CI, 0.70-1.10]; in-hospital mortality: aOR, 0.84 [95%CI, 0.69-1.01]). Of note, the exact time of last NOAC dose was not measured in this registry, and levels of factor Xa were also not available. Based on an analysis of a smaller registry used within this study which reported time of NOAC dose, a large majority of NOAC patients treated with lysis had taken their last dose more than 24 hours prior to the stroke event.

Fluoxetine in Stroke Fails to Deliver

Muhammad Rizwan Husain, MD
@RIZWANHUSAINMD  

Lundström E, Isaksson E, Greilert Norin N, Näsman P, Wester P, Mårtensson B, Norrving B, Wallén H, Borg J, Hankey GJ, et al. Effects of Fluoxetine on Outcomes at 12 Months After Acute Stroke: Results From EFFECTS, a Randomized Controlled Trial. Stroke. 2021.

The Efficacy oF Fluoxetine—a randomisEd Controlled Trial in Stroke (EFFECTS) was a randomized clinical trial whose primary outcome was to assess if oral fluoxetine initiated within 2-15 days of an acute stroke (ischemic or hemorrhagic) and taken up to 6 months improved functional outcomes. The initial trial results, which were published in August 2020, demonstrated no improvement in functional outcomes (modified Rankin Score-mRS-adjusted odds ratio: 0.94 [95% CI 0.78–1.13]) at 6 months with fluoxetine use and noted an increased rate of fractures and hyponatremia, though occurrence of depression was reduced (by 4%).

The authors now report 12-month follow-up results on outcomes that include the mRS, health status, quality of life, fatigue, mood and depression to see if any effects of fluoxetine persisted or were delayed.

Article Commentary: “Switching to Tenecteplase for Stroke Thrombolysis: Real-World Experience and Outcomes in a Regional Stroke Network”

Ericka Samantha Teleg, MD

Mahawish K, Gommans J, Kleinig T, Lallu B, Tyson A, Ranta A. Switching to Tenecteplase for Stroke Thrombolysis: Real-World Experience and Outcomes in a Regional Stroke Network. Stroke. 2021.

Accessibility to stroke services, timely treatment and management differ in regions and locations throughout the world. Each geographic location is different in terms of barriers to stroke treatment. Evidence translated to real-world findings is an important key element in this article by Mahawish et al. The New Zealand Central Region Hyper-Acute Stroke Network switched to tenecteplase driven by data supporting probable improvement of large vessel occlusion (LVO) recanalization in areas wherein, first, endovascular accessibility is a challenge due to geographical limitations, and second, the ease of tenecteplase administration. This model can contribute to other regions that have similar landscape in terms of medical resources and accessibility to tertiary or regional centers with endovascular administration infrastructure.

Does Thrombus Equal Thrombus? Mechanical Characterization of Thrombi Retrieved During Endovascular Thrombectomy in Stroke Patients

Tolga D. Dittrich, MD

Boodt N, Snouckaert van Schauburg PRW, Hund HM, Fereidoonnezhad B, McGarry JP, Akyildiz AC, van Es ACGM, De Meyer SF, Dippel DWJ, Lingsma HF, et al. Mechanical Characterization of Thrombi Retrieved With Endovascular Thrombectomy in Patients With Acute Ischemic Stroke. Stroke. 2021;52:2510–2517.

Mechanical thrombectomy (MT) for acute stroke has made remarkable advances over the last few years. Despite technological improvements, revascularization still is not successful in a considerable fraction of treated patients. This inevitably raises the question of why MT is so difficult in some patients and how we might treat them better in the future.

An important starting point could be a more comprehensive understanding of the biological composition of thrombi and their mechanical properties. Experimental studies have shown that increasing thrombus stiffness is associated with unsuccessful or incomplete recanalization. For example, particularly stiff platelet-rich thrombi could not be removed by aspiration alone or combined with a stent retriever in an animal model.

Tenecteplase for Thrombolysis of Acute Ischemic Stroke: The Debate Continues

Ammad Mahmood, MBChB
@AMahmoodNeuro

Putaala J, Saver JL, Nour M, Kleindorfer D, McDermott M, Kaste M. Should Tenecteplase be Given in Clinical Practice for Acute Ischemic Stroke Thrombolysis? Stroke. 2021;52:3075–3080.

Guaranteed to feature on the program at this year’s stroke meetings (virtual or otherwise), the debate regarding the potential use of tenecteplase for thrombolysis in acute ischemic stroke rolls on. The authors of this commentary present an excellent summary of the pros and cons of choosing tenecteplase over alteplase, summarizing and critiquing the evidence base in both camps, before reaching a balanced conclusion reflecting the current equipoise in the stroke community.

Article Commentary: “Treatment and Outcomes of Patients With Ischemic Stroke During COVID-19”

Ericka Teleg, MD

Srivastava PK, Zhang S, Xian Y, Xu H, Rutan C, Alger HM, Walchok JG, Williams JH, de Lemos JA, Decker-Palmer MR, et al. Treatment and Outcomes of Patients With Ischemic Stroke During COVID-19: An Analysis From Get With The Guidelines-Stroke. Stroke. 2021.

The COVID-19 pandemic has caused a shift in stroke systems and has changed the way stroke approach and management are put in place. The impact of this is that time is still brain. Time and stroke outcomes still matter more so during this time. From a patient’s perspective in experiencing and reporting symptoms to the way emergency room systems tackle stroke during the pandemic, remain a challenge.

The objective of this study was to analyze characteristics, evaluation, treatment, and in-hospital outcomes of patients presenting with acute ischemic stroke pre-COVID-19 and during COVID-19 time. This study is important as it allows us to be able to navigate the time-sensitive nature of stroke during COVID-19. With the COVID-19 restrictions and concern for infection and transmission, several studies have demonstrated no difference in diagnostic and treatment times pre-COVID 19 versus the COVID-19 era. On the other hand, some studies showed a decline in stroke presentations. One reason emphasized in this article is underreporting of symptoms due to fear of COVID-19 exposure in-hospital.

The Reversibly Stunned Brain After Successful Endovascular Reperfusion in Acute Anterior Circulation Ischemic Stroke

Tolga D. Dittrich, MD

Talavera B, Gómez-Vicente B, Martínez-Galdámez M, López-Cancio E, García-Cabo C, Castellanos M, Roel A, Tejada-Meza H, Marta-Moreno J, Pérez-Lázaro C, et al. Delayed Neurological Improvement After Full Endovascular Reperfusion in Acute Anterior Circulation Ischemic Stroke. Stroke. 2021;52:2210-2217.

Endovascular thrombectomy (EVT) is an essential part of acute therapy for ischemic stroke due to large vessel occlusion. As early clinical improvement after successful reperfusion therapy is a reliable predictor of long-term independence, the absence of such clinical progress can discourage the treating stroke team. But does this necessarily mean that the long-term prognosis in such patients is unfavorable? This is one of the questions addressed by Talavera et al. in their paper.

A total of 628 patients with proximal occlusions of the anterior circulation, all of whom received successful EVT (i.e., mTICI 3), were included in the study. After EVT, 142 (22.6%) showed no early neurological improvement. However, 32 (22.5%) still had a favorable long-term outcome. In contrast, 323 (66.5%) of a total of 486 patients with early neurological improvement demonstrated a favorable long-term outcome. Baseline predictors of delayed neurological improvement were male sex (OR 6.4 [95% CI, 2.1-22.3] p=.002), lower baseline NIHSS score (OR 1.4 [95% CI, 1.2-1.5]. p=<.001) and treatment with rtPA (OR 9.1, [95% CI, 2.7-30.9], p=<.001).