American Heart Association

Pooled Risk-Benefit Analysis of Long-Term Antiplatelet Therapies for Non-Cardioembolic Transient Ischemic Attack or Stroke

Dixon Yang, MD

Hilkens NA, Algra A, Diener HC, Bath PM, Csiba L, Hacke W, Kappelle LJ, Koudstaal PJ, Leys D, Mas J-L, et al. Balancing Benefits and Risks of Long-Term Antiplatelet Therapy in Noncardioembolic Transient Ischemic Attack or Stroke. Stroke. 2021.

Aspirin monotherapy, aspirin with dipyridamole, and clopidogrel alone are the first-line antithrombotic therapies for long-term secondary prevention of non-cardioembolic stroke and transient ischemic attack (TIA). In clinical practice, we often consider an individual patient’s bleeding risks against potential benefits of reduced ischemic events from these single antiplatelet agents. Assessing risk-benefit by stratification of bleeding risk may help guide clinical decision-making. Therefore, Hilkens et al. sought to investigate the net benefit of antiplatelet treatment according to an individual’s bleeding risk through pooled analysis of six randomized control trials.

The authors pooled individual patient data from CAPRIE, ESPS-2, MATCH, CHARISMA, ESPRIT, and PRoFESS, which investigated antiplatelet therapy in the subacute or chronic phase after non-cardioembolic stroke or TIA. The authors stratified patients into quintiles by their individually calculated S2TOP-BLEED score, derived from sex, smoking, modified Rankin Scale, prior stroke, hypertension, body mass index, age, and diabetes. For each quintile, the authors determined the annual rate of major bleeding and recurrent ischemic events of: 1) aspirin monotherapy; 2) aspirin-clopidogrel versus monotherapy; 3) aspirin-dipyridamole versus clopidogrel; and 4) aspirin versus clopidogrel. In the second, third, and fourth comparisons, the authors calculated net benefit.

Anti-Hypertensive Drugs for Secondary Prevention of Stroke: Is It Time to Move On?

Wern Yew Ding, MBChB

Boncoraglio GB, Del Giovane C, Tramacere I. Antihypertensive Drugs for Secondary Prevention After Ischemic Stroke or Transient Ischemic Attack: A Systematic Review and Meta-Analysis. Stroke. 2021;52:1974–1982.

Hypertension is well-recognized as a major risk factor for primary and recurrent strokes. Previous studies have shown that the use of blood pressure (BP)-lowering drugs among patients who have suffered an initial stroke is beneficial at reducing the risk of recurrent stroke, regardless of whether or not these patients had a documented history of hypertension. However, there is limited evidence focusing on patients with ischemic stroke (instead of all stroke types).

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: “Targeting Cardiac Disease in Stroke Prevention: Joint Session With the European Society of Cardiology (ESC)”

Thomas Meinel, MD
@TotoMynell

European Stroke Organisation Conference
September 1–3, 2021

Stroke prevention — especially in patients with atrial fibrillation — is a team effort of cardiologists and vascular neurologists. Vice-versa, work-up of cardiac disease and cardioaortic sources of embolism is a joint effort of stroke physicians and cardiologists. Several novel diagnostic options, medical therapies and devices are available in the cardiovascular field. Hence, this joint session of the ESO and ESC was a logical consequence of intensified collaboration of these two big societies.

The first speaker was Marta Rubiera from Spain, who elaborated on the diagnostic options to identify structural cardioaortic sources of embolism in stroke patients. Presenting the expected diagnostic findings and weighing nicely the pros and cons of each modality, she guided the audience to choose the correct test according to the patient and the stroke characteristics. Cardiac MRI and cardiac CT represent novel diagnostic options in selected patients, but echocardiography remains the working horse of stroke work-up. However, the lack of randomized diagnostic studies with clinical outcomes and the uncertainty of what to do with minor sources of embolism remain a major drawback of this daily task during stroke unit rounds. Joint efforts of cardiology and neurology are necessary to overcome this evidence gap.

ESOC 2021 Session: “Large Artery Stroke: Carotid Disease, Plaque and Beyond”

Karissa Arthur, MD

European Stroke Organisation Conference
September 1–3, 2021

Cervical Artery Dissection: Christopher Traenka, University Hospital Basel

Dr. Traenka discussed carotid artery dissection (CeAD) in this talk. He first discussed CeAD and sports. Patients with CeAD obtained during stroke should refrain from any sports activities for at least one month, and this period may need to be prolonged considering the patient’s clinical course. When resuming activities, patients should start at low intensity and gradually increase activity. Most patients will go back to full activity in 6-12 months.

ESOC 2021 Session: “Closing Ceremony and Large Clinical Trials 2”

Vignan Yogendrakumar, MD, MSc
@VYogendrakumar

European Stroke Organisation Conference
September 1–3, 2021

Wrapping up our coverage of this year’s ESOC, the second round of results from major clinical trials!

APACHE-AF: Apixaban after Anticoagulation-Associated Intracerebral Hemorrhage In Patients with Atrial Fibrillation: A Randomized, Open-Label, Phase 2 Trial

APACHE-AF was a prospective, randomized, open-label clinical trial, recruiting adults with a history of atrial fibrillation and anticoagulation associated ICH. Following their ICH event (days 7-90 days post ICH event), participants were randomized to apixaban 5mg twice daily or to avoiding anticoagulation. Primary outcome was vascular death or non-fatal stroke and was evaluated using a Cox proportional hazards regression model. Between January 16, 2015 and July 6, 2020, 101 participants (46% female, median age 77 years) were recruited at a median of 46 (IQR 21-74) days after ICH in an intention to treat analysis. Participants were followed for a median of 1.9 (IQR 1.0-3.1) years. There were 10 patients who crossed over. For the primary outcome, comparing Apixaban to Avoiding Anticoagulation: Adjusted HR: 1.05 (0.48-2.31), indicating no major difference between the two groups. There were no major differences in subsequent ICH between the two groups.

ESOC 2021 Session: “Presidential Symposium Awards and Large Clinical Studies”

Thomas Meinel, MD
@TotoMynell

European Stroke Organisation Conference
September 1–3, 2021

The first part of the symposium was the awards ceremony for the presidential awards for 2021 and 2020 for exceptional late-stage researchers. The awardees were Professor Michael Brainin, past ESO and WSO president and founder of the ESO European Stroke Master programme, followed by Professor Bo Norrving, editor-in-chief of the European Stroke Journal, ESO founding member, past WSO president, and past ESO vice-president. Both were honored for their outstanding contributions to both stroke research and development of the ESO.

Next up were the awardees of the Scientific Excellence Award of 2021 and 2020. The first awardee was Professor Georgios Tsivgoulis, the vice-president of ESO. He not only contributed significantly to the recent guidelines on intravenous thrombolysis and blood pressure management, but he also has an impressive scientific track record with a special focus on evidence synthesis. The second awardee was Professor Urs Fischer, the former ESO secretary general. He is the principal investigator of several multicenter international trials answering burning questions of present stroke care with important results presented at this conference. Both awardees pointed out that clinical research is a team effort and dedicated their award to the study teams, collaborators, and PhD students.

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.