Standard or Low Dose Alteplase in Acute Ischemic Stroke–Does It Matter?

MedicalResearch.com Interview with:

Craig Anderson | MD PhD FRACP Executive Director  Professor of Neurology and Epidemiology, Faculty of Medicine, UNSW Sydney Neurologist, Neurology Department, Royal Prince Alfred Hospital The George Institute for Global Health at Peking University Health Science Center Haidian District | Beijing, 100088 P.R. China

Prof. Anderson

Craig Anderson | MD PhD FRACP
Executive Director
Professor of Neurology and Epidemiology, Faculty of Medicine, UNSW Sydney
Neurologist, Neurology Department, Royal Prince Alfred Hospital
The George Institute for Global Health at Peking University Health Science Center
Haidian District | Beijing, 100088 P.R. China

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:  There is much controversy over the benefits of a lower dose of intravenous alteplase, particularly in Asia, after the Japanese regulatory authorities approved a dose of 0.6 mg/kg 10 years ago compared to the US FDA and other regulatory authorities approving 0.9 mg/kg 20 years ago.  The investigator inititiated and conducted ENCHANTED trial aimed to determine the effectiveness and safety of these two doses in an international multicentre pragmatic open design.

The main results did not confirm the low-dose to be statistically ‘non-inferior’ partly due to the primary outcome measure chosen and partly due to the statistical approach, but it did confirm that the lower dose was safer with less risk of the major complication of this treatment, that of major bleeding in the brain.  However, it would appear that this safety effect was offset by some reduce efficacy in terms of functional recovery.

The aim of this secondary analysis of the trial data was to examine in more detail the differences between low and standard dose alteplase according to the participants’ age, ethnicity (Asian vs non-Asian) and severity of neurological deficit at the time of treatment.  We did this because the popular belief is that a lower dose might be preferred in older people, and Asians, because of the potential for more likelihood of bleeding, and preferentially to use the standard dose in those with more severe strokes potentially due to greater ‘clot burden’ from a blocked artery to the brain.

The results showed that the main findings on the outcome of surviving free of disability were the same according to age, ethnicity and stroke severity – that is, there was no preferential dose in any of these groups.  Similarly, the safety benefit of low dose alteplase on brain haemorrhage, did not clearly translate into clinical disability outcomes in any of the patient groups studied.

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Ischemic Stroke As Cancer Predecessor and Associated Predictors

MedicalResearch.com Interview with:

Jacobo Rogado

Dr. Rogado

Dr Jacobo Rogado
Medical oncology fellow
Hospital de La Princesa
Madrid, Spain

MedicalResearch.com: What is the background for this study?

Response: Some publications have suggested that there is an association between stroke and the subsequent diagnosis of cancer, although others have not confirmed this.

We have addressed this issue with a study conducted at our hospital during two years. We studied a population of about 1000 patients with stroke. We evaluated the incidence of cancer in this population during the follow-up of 18 months, as well as whether there were factors associated with its occurrence.

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Which Is Better? Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke

MedicalResearch.com Interview with:

Prof. Jean-Louis MAS Université Paris Descartes INSERM UMR S 894 Service de Neurologie et Unité Neurovasculaire Hôpital Sainte-Anne Paris 

Prof. Jean Louis MAS

Prof. Jean-Louis MAS
Université Paris Descartes
INSERM UMR S 894
Service de Neurologie et Unité Neurovasculaire
Hôpital Sainte-Anne
Paris 

MedicalResearch.com: What is the background for this study?

Response: Stroke is a major cause of death, disability and dementia affecting 17 million people each year worldwide. About 80% of strokes are ischemic strokes due to occlusion of a cerebral artery by a thrombus, itself the consequence of various arterial or heart diseases. In 30 to 40% of cases, no definite cause of ischemic stroke can be identified. Cryptogenic stroke is the term used to refer to these strokes of unknown etiology.

The patent foramen ovale (PFO) is a defect between the upper two heart chambers (called atria) though which a thrombus of venous origin may reach the systemic circulation and cause a stroke. This mechanism is called paradoxical embolism. Several case-control studies have shown an association between PFO and cryptogenic ischemic stroke, particularly in patients less than 60 years old, in those who have an atrial septal aneurysm (defined as an abnormal protrusion of the interatrial septum in the right or the left atrium or both) in addition to a PFO, and in those who have a PFO with a large right-to-left shunt. These findings suggested that a PFO might be responsible for stroke and that PFO closure with a device may decrease the risk of stroke recurrence. However, the causative relationship between PFO and stroke and the best strategy to prevent stroke recurrence have long been a hot topic of debate. Three previous randomized clinical trials failed to demonstrate any superiority of PFO closure over antithrombotic therapy.

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CDC Reports Progress In Reducing Strokes Has Stalled

MedicalResearch.com Interview with:

Quanhe Yang, PhD Division for Heart Disease and Stroke Prevention National Center for Chronic Disease Prevention and Health Promotion CDC

Dr. Yang

Quanhe Yang, PhD
Division for Heart Disease and Stroke Prevention
National Center for Chronic Disease Prevention and Health Promotion
CDC

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The prominent decline in U.S. stroke death rates observed for more than 4 decades has slowed in recent years. CDC examined trends and patterns in recent stroke death rates among U.S. adults aged ≥ 35 years by age, sex, race/ethnicity, state, and census region.

Declines in stroke death rates have slowed down in 3 out of every 4 states from 2000 to 2015, and the stroke death rates increased significantly in southern states and among Hispanics from 2013 to 2015.

An estimated 30,000 excess stroke deaths might have occurred because of the unfavorable changes in the rate of decline in stroke mortality during 2013–2015.

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ASTER Study Opens Door To New Tool To Remove Clot in Ischemic Stroke

MedicalResearch.com Interview with:
Bertrand LAPERGUE, MD, PhD
Hôpital Foch, University Versailles Saint Quentin en Yvelynes
Department of Stroke Center, Diagnostic and Interventional Neuroradiology
Suresnes, France.
Michel PIOTIN, MD
Department of Diagnostic and Interventional Neuroradiology
Fondation Rothschild, Paris, France.
on behalf of the ASTER Trial Investigators.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Mechanical thrombectomy (MT) with a stent retriever (SR), in association with intravenous (IV) rtPA, is now the standard of care in anterior circulation ischemic stroke caused by large vessel occlusion (LVO).

Favorable outcome is strongly associated with the successful reperfusion status (TICI 2b/3= 71% with SR, Hermes Study group).
New techniques for MT such as ADAPT (A Direct first pass Aspiration Technique) seem promising to increase reperfusion status and clinical outcome in retrospective studies.

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Obesity Paradox: Overweight and Mildly Obese Stroke Patients Have Better Prognosis

MedicalResearch.com Interview with:

Hugo J. Aparicio, MD, MPH Assistant Professor Vascular Neurology, Department of Neurology Investigator, The Framingham Heart Study www.framinghamheartstudy.org Boston University School of Medicine Boston, MA 02118-2526

Dr. Aparicio

Hugo J. Aparicio, MD, MPH
Assistant Professor
Vascular Neurology, Department of Neurology
Investigator, The Framingham Heart Study
www.framinghamheartstudy.org
Boston University School of Medicine
Boston, MA 02118-2526

MedicalResearch.com: What is the background for this study?

Response: The association of body weight with survival after stroke has been studied before and is a controversial topic. Results have varied between studies and have often been contradictory. The observational findings that carrying extra weight can be protective after having a disease, like stroke or heart attack, has been called an obesity paradox, since obesity in itself is a risk factor for cardiovascular disease and mortality in the general population. Stroke research has focused on hospitalized stroke patients with weight measured at the time of the stroke. BMI is often missing in this group of patients, especially when a stroke is severe or the patients cannot report their weight. In the FHS we have data regarding weight prior to stroke, obtained during regularly scheduled research exams, with multiple data points on body weight and vascular risk factors over time. All before the stroke occurs. And have also compared survival outcomes with a group of control participants, those without stroke, to see if the so-called ‘obesity paradox’ is a non-specific finding seen in older adults or seen specifically in stroke patients.

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Does Head Positioning Matter In Acute Stroke?

MedicalResearch.com Interview with:

Craig Anderson | MD PhD FRACP Executive Director  Professor of Neurology and Epidemiology, Faculty of Medicine, UNSW Sydney Neurologist, Neurology Department, Royal Prince Alfred Hospital The George Institute for Global Health at Peking University Health Science Center Haidian District | Beijing, 100088 P.R. China

Prof. Anderson

Craig Anderson | MD PhD FRACP
Executive Director
Professor of Neurology and Epidemiology, Faculty of Medicine, UNSW Sydney
Neurologist, Neurology Department, Royal Prince Alfred Hospital
The George Institute for Global Health at Peking University Health Science Center
Haidian District | Beijing, 100088 P.R. China

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Preliminary small studies indicate that lying flat increases blood flow and oxygenation to the brain.  Thus, patients with acute ischemic stroke may benefit from lying flat in bed.  Conversely, sitting up in bed, with the head elevated to at least 30 degrees, may reduce swelling in the brain for patients who have large ischemic or hemorrhagic forms of stroke.  The optimal head position to produce the best outcome from acute stroke, and avoid potential risks, such as aspiration pneumonia, is unknown.  We undertook a large scale multicentre randomized controlled trial where 114 hospitals were randomised to sequentially apply lying flat or sitting up head positioning as a policy of care to a consecutive series of patients, that overall totalled over 11000 patients, presenting with acute stroke.  The study showed there was no difference in the chance of good physical recovery for patients between the two head positions but also that there were no excessive harms for either.

In other words, head positioning alone didn’t produce any benefits or harms in patients with acute stroke

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Intensive Blood Pressure Reduction and Spot Sign in Intracerebral Hemorrhage

MedicalResearch.com Interview with:
Andrea Morotti, M.D.
Research Fellow in Neurology
Massachusetts General Hospital
Harvard Medical School

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The CT angiography (CTA) spot sign is a validated marker of Intracerebral Hemorrhage (ICH) expansion and may identify those subjects more likely to benefit from intensive blood pressure reduction.

We observed that less than 20% of ICH patients received a CTA as part of their diagnostic workup in a large, international randomized clinical trial. The performance of the spot sign in predicting ICH growth was suboptimal compared with what was reported in previous studies. Intensive blood pressure reduction did not improve functional outcome in spot sign positive patients.

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Increase In Risk Factors Contribute To More Strokes in Rural Areas

MedicalResearch.com Interview with:

George Howard, Dr.PH PI of the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study Department of Biostatistics University of Alabama at Birmingham Birmingham, AL

Dr. Howard

George Howard, Dr.PH
PI of the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study
Department of Biostatistics
University of Alabama at Birmingham
Birmingham, AL

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Rural areas have been known to have a higher death rate than urban, and higher death from stroke in rural areas is a major contributor to this disparity.

The goal of the research was to assess if the higher deaths from stroke was because rural people are more likely to have a stroke, or more likely to die from a stroke once it occurs.   This distinction is critically important, since intervention to reduce stroke deaths in rural area would focus on stroke prevention if the former, but would focus on improving stroke care (after the stroke) if the latter.

We found that the higher mortality from stroke appears to be almost completely due to more people having stroke.   As such, we need to focus on efforts to reduce the risk of rural areas.   While there are well-documented differences in stroke care between urban and rural areas, resolving these differences will not be likely reduce the rural excess death from stroke.

It would seem that the higher risk of having a stroke could be due to the observation that those in rural areas are more likely to have major stroke risk factors, including hypertension, diabetes and cigarette smoking; however, the higher prevalence of these risk factors don’t seem to explain the higher risk.   So what causes the higher risk remains a mystery.

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Comparison of NOACs with Warfarin In Atrial Fibrillation Patients With Single Stroke Risk Factor

MedicalResearch.com Interview with:

Gregory Y. H. Lip, MD Professor of Cardiovascular Medicine University of Birmingham, UK; Adjunct Professor of Cardiovascular Sciences, Thrombosis Research Unit, Aalborg University, Denmark National Institute for Health Research (NIHR) Senior Investigator. Visiting Professor of Haemostasis Thrombosis & Vascular Sciences, Aston University, Birmingham, UK Visiting Professor of Cardiology, University of Belgrade, Serbia; Visiting Professor, University of Leeds, UK Honorary Professor, Chinese PLA Medical School, Beijing, China; Honorary Professor, Nanjing Medical University, Nanjing, China; Visiting Professor, National Yang-Ming University, Taipei, Taiwan Institute of Cardiovascular Sciences City Hospital Birmingham England UK

Dr. Lip

Gregory Y. H. Lip, MD
Professor of Cardiovascular Medicine
University of Birmingham
Adjunct Professor of Cardiovascular Sciences, Thrombosis Research Unit, Aalborg University, Denmark
National Institute for Health Research (NIHR) Senior Investigator.
Visiting Professor of Haemostasis Thrombosis & Vascular Sciences, Aston University, Birmingham, UK
Institute of Cardiovascular Sciences
City Hospital
Birmingham England UK

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The randomized clinical trials comparing non-Vitamin K antagonist oral anticoagulants (NOACs) vs warfarin largely focused on recruitment of high risk atrial fibrillation(AF) patients with >2 stroke risk factors, with only the trials testing dabigatran or apixaban including a minority of patients with 1 stroke risk factor.

Despite this, regulatory approvals of all NOACs have been for stroke prevention in AF patients with ≥1 stroke risk factors. No difference between NOACs compared to warfarin in risk of ischemic stroke/systemic embolism, was seen but for ‘any bleeding’, this was lower for apixaban and dabigatran compared to warfarin.

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