-
Continuum (Minneapolis, Minn.) Apr 2020The article "Update on Treatment of Acute Ischemic Stroke" by Dr Rabinstein was first published in the February 2017 Cerebrovascular Disease issue of Continuum: Lifelong... (Review)
Review
EDITOR'S NOTE
The article "Update on Treatment of Acute Ischemic Stroke" by Dr Rabinstein was first published in the February 2017 Cerebrovascular Disease issue of Continuum: Lifelong Learning in Neurology as "Treatment of Acute Ischemic Stroke" and has been updated by Dr Rabinstein for this issue at the request of the Editor-in-Chief.
ABSTRACT
PURPOSE OF REVIEWThis article provides an update on the state of the art of the treatment of acute ischemic stroke with particular emphasis on the indications for reperfusion therapy.RECENT FINDINGSIn addition to the previously established indications for intravenous (IV) thrombolysis with recombinant tissue plasminogen activator (rtPA) within 4.5 hours of stroke symptom onset and endovascular therapy with mechanical thrombectomy for patients with large artery occlusion who can be treated within 6 hours of symptom onset, recent randomized controlled trials have now established new indications for emergency reperfusion in patients with wake-up stroke or delayed presentation (up to 24 hours from last known well in the case of mechanical thrombectomy). Identification of patients who may benefit from acute reperfusion therapy within this extended time window requires screening with perfusion brain imaging or, in the case of IV thrombolysis for wake-up strokes, emergency brain MRI. Collateral status and time to reperfusion remain the primary determinants of outcome.SUMMARYTimely successful reperfusion is the most effective treatment for patients with acute ischemic stroke. Recent evidence supports the expansion of the time window for reperfusion treatment in carefully selected patients.
Topics: Fibrinolytic Agents; Humans; Ischemic Stroke; Mechanical Thrombolysis; Outcome and Process Assessment, Health Care; Reperfusion; Thrombolytic Therapy
PubMed: 32224752
DOI: 10.1212/CON.0000000000000840 -
Intensive Care Medicine Apr 2021The European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) have collaborated to produce these post-resuscitation care...
The European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) have collaborated to produce these post-resuscitation care guidelines for adults, which are based on the 2020 International Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations. The topics covered include the post-cardiac arrest syndrome, diagnosis of cause of cardiac arrest, control of oxygenation and ventilation, coronary reperfusion, haemodynamic monitoring and management, control of seizures, temperature control, general intensive care management, prognostication, long-term outcome, rehabilitation and organ donation.
Topics: Adult; Cardiopulmonary Resuscitation; Critical Care; Heart Arrest; Humans; Myocardial Reperfusion; Resuscitation; Seizures
PubMed: 33765189
DOI: 10.1007/s00134-021-06368-4 -
European Heart Journal Apr 2023During the last 5-7 years, tremendous progress was achieved in the reperfusion treatment of acute ischaemic stroke during its first few hours from symptom onset. This... (Review)
Review
During the last 5-7 years, tremendous progress was achieved in the reperfusion treatment of acute ischaemic stroke during its first few hours from symptom onset. This review summarizes the latest evidence from randomized clinical trials and prospective registries with a focus on endovascular treatment using stent retrievers, aspiration catheters, thrombolytics, and (in selected patients) carotid stenting. Novel approaches in prehospital (mobile interventional stroke teams) and early hospital (direct transfer to angiography) management are described, and future perspectives ('all-in-one' laboratories with angiography and computed tomography integrated) are discussed. There is reasonable chance for patients with moderate-to-severe acute ischaemic stroke to survive without permanent sequelae when the large-vessel occlusion is removed by means of modern pharmaco-mechanic approach. Catheter thrombectomy is now the golden standard of acute stroke treatment. The role of cardiologists in stroke is expanding from diagnostic help (to reveal the cause of stroke) to acute therapy in those regions where such up-to-date Class I. A treatment is not yet available.
Topics: Humans; Stroke; Brain Ischemia; Prospective Studies; Endovascular Procedures; Thrombectomy; Ischemic Stroke; Stents; Reperfusion; Treatment Outcome
PubMed: 36477996
DOI: 10.1093/eurheartj/ehac684 -
Journal of Cardiology Feb 2023Owing to recent advances in early reperfusion strategies, pharmacological therapy, standardized care, and the identification of vulnerable patient subsets, the prognosis... (Review)
Review
Owing to recent advances in early reperfusion strategies, pharmacological therapy, standardized care, and the identification of vulnerable patient subsets, the prognosis of acute myocardial infarction has improved. However, there is still considerable room for improvement. This review article summarizes the latest evidence concerning clinical diagnosis and treatment of acute myocardial infarction.
Topics: Humans; Myocardial Infarction; Myocardial Reperfusion; Thrombolytic Therapy; Prognosis; Percutaneous Coronary Intervention; Treatment Outcome; Myocardial Revascularization
PubMed: 35882613
DOI: 10.1016/j.jjcc.2022.07.003 -
Oxidative Medicine and Cellular... 2021Myocardial ischemia is a disease with high morbidity and mortality, for which reperfusion is currently the standard intervention. However, the reperfusion may lead to... (Review)
Review
Myocardial ischemia is a disease with high morbidity and mortality, for which reperfusion is currently the standard intervention. However, the reperfusion may lead to further myocardial damage, known as myocardial ischemia/reperfusion injury (MI/RI). Oxidative stress is one of the most important pathological mechanisms in reperfusion injury, which causes apoptosis, autophagy, inflammation, and some other damage in cardiomyocytes through multiple pathways, thus causing irreversible cardiomyocyte damage and cardiac dysfunction. This article reviews the pathological mechanisms of oxidative stress involved in reperfusion injury and the interventions for different pathways and targets, so as to form systematic treatments for oxidative stress-induced myocardial reperfusion injury and make up for the lack of monotherapy.
Topics: Humans; Myocardial Ischemia; Oxidative Stress; Reperfusion
PubMed: 34055195
DOI: 10.1155/2021/6614009 -
Nature Reviews. Neurology Apr 2022For over 40 years, attempts to develop treatments that protect neurons and other brain cells against the cellular and biochemical consequences of cerebral ischaemia in... (Review)
Review
For over 40 years, attempts to develop treatments that protect neurons and other brain cells against the cellular and biochemical consequences of cerebral ischaemia in acute ischaemic stroke (AIS) have been unsuccessful. However, the advent of intravenous thrombolysis and endovascular thrombectomy has taken us into a new era of treatment for AIS in which highly effective reperfusion therapy is widely available. In this context, cytoprotective treatments should be revisited as adjunctive treatment to reperfusion therapy. Renewed efforts should focus on developing new drugs that target multiple aspects of the ischaemic cascade, and previously developed drugs should be reconsidered if they produced robust cytoprotective effects in preclinical models and their safety profiles were reasonable in previous clinical trials. Several development pathways for cytoprotection as an adjunct to reperfusion can be envisioned. In this Review, we outline the targets for cytoprotective therapy and discuss considerations for future drug development, highlighting the recent ESCAPE-NA1 trial of nerinetide, which produced the most promising results to date. We review new types of clinical trial to evaluate whether cytoprotective drugs can slow infarct growth prior to reperfusion and/or ameliorate the consequences of reperfusion, such as haemorrhagic transformation. We also highlight how advanced brain imaging can help to identify patients with salvageable ischaemic tissue who are likely to benefit from cytoprotective therapy.
Topics: Brain; Brain Ischemia; Cytoprotection; Endovascular Procedures; Humans; Ischemic Stroke; Reperfusion; Stroke; Thrombectomy; Treatment Outcome
PubMed: 35079135
DOI: 10.1038/s41582-021-00605-6 -
FP Essentials Jan 2022Urgent evaluation of patients with acute ischemic stroke allows for a comprehensive assessment of management options. These include thrombolysis and thrombectomy,...
Urgent evaluation of patients with acute ischemic stroke allows for a comprehensive assessment of management options. These include thrombolysis and thrombectomy, depending on symptom onset and severity, the presumed location of the occlusion, and patient comorbidities and potential for improvement. For patients who present within 4.5 hours of onset of disabling symptoms consistent with acute ischemic stroke and with no contraindications, intravenous thrombolysis is indicated. Acute mechanical thrombectomy may be indicated for patients who present within 24 hours of symptom onset and have symptoms consistent with a large vessel occlusion. After reperfusion therapy, patients require close neurologic monitoring. Patients who receive reperfusion therapy tend to have better functional outcomes than patients who do not. Secondary prevention includes use of antithrombotics and glycemic control. Common issues in the acute setting include cerebral edema, hemorrhagic transformation, and symptomatic carotid disease.
Topics: Brain Ischemia; Hospitals; Humans; Reperfusion; Stroke; Thrombectomy
PubMed: 35006662
DOI: No ID Found -
JAMA Sep 2021Mechanical thrombectomy using a stent retriever or contact aspiration is widely used for treatment of patients with acute ischemic stroke due to anterior circulation... (Comparative Study)
Comparative Study Randomized Controlled Trial
Effect of Thrombectomy With Combined Contact Aspiration and Stent Retriever vs Stent Retriever Alone on Revascularization in Patients With Acute Ischemic Stroke and Large Vessel Occlusion: The ASTER2 Randomized Clinical Trial.
IMPORTANCE
Mechanical thrombectomy using a stent retriever or contact aspiration is widely used for treatment of patients with acute ischemic stroke due to anterior circulation large vessel occlusion, but the additional benefit of combining contact aspiration with stent retriever is uncertain.
OBJECTIVE
To determine whether mechanical thrombectomy for treatment of anterior circulation large vessel occlusion stroke with initial contact aspiration and stent retriever combined results in better final angiographic outcome than with standard stent retriever alone.
DESIGN, SETTING, AND PARTICIPANTS
This trial was a multicenter randomized, open-label, blinded end point evaluation that enrolled 408 patients from October 16, 2017, to May 29, 2018, in 11 French comprehensive stroke centers, with a 12-month outcome follow-up. Patients with a large vessel occlusion in the anterior circulation were included up to 8 hours after symptom onset. The final date of follow-up was June, 19, 2019.
INTERVENTIONS
Patients were randomly assigned (1:1 allocation) to receive initial thrombectomy with contact aspiration and stent retriever combined (205) or stent retriever alone (203).
MAIN OUTCOMES AND MEASURES
The primary outcome was the rate of expanded Thrombolysis In Cerebral Infarction score of 2c or 3 (eTICI 2c/3; ie, scores indicate near-total and total reperfusion grades) at the end of the procedure.
RESULTS
Among the 408 patients who were randomized, 3 were excluded, and 405 (99.3%) patients (mean age, 73 years; 220 [54%] women and 185 [46%] men) were included in the primary analysis. The rate of eTICI 2c/3 at the end of the endovascular procedure was not significantly different between the 2 thrombectomy groups (64.5% [131 of 203 patients] for contact aspiration and stent retriever combined vs 57.9% [117 of 202 patients] for stent retriever alone; risk difference, 6.6% [95% CI, -3.0% to 16.2%]; adjusted odds ratio [OR], 1.33 [95% CI, 0.88 to 1.99]; P = .17). Of 14 prespecified secondary efficacy end points, 12 showed no significant difference. A higher rate of successful reperfusion was achieved in the contact aspiration combined with stent retriever group vs the stent retriever alone group (eTICI 2b50/2c/3, 86.2% vs 72.3%; adjusted OR, 2.54 [95% CI, 1.51 to 4.28]; P < .001) and of near-total or total reperfusion (eTICI 2c/3, 59.6% vs 49.5%; adjusted OR, 1.52 [95% CI, 1.02 to 2.27]; P = .04) after the assigned initial intervention alone.
CONCLUSIONS AND RELEVANCE
Among patients with acute ischemic stroke due to large vessel occlusion, an initial thrombectomy technique consisting of contact aspiration and stent retriever combined, compared with stent retriever alone, did not significantly improve the rate of near-total or total reperfusion (eTICI 2c/3) at the end of the endovascular procedure, although the trial may have been underpowered to detect smaller differences between groups.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03290885.
Topics: Aged; Arterial Occlusive Diseases; Combined Modality Therapy; Device Removal; Female; Humans; Ischemic Stroke; Male; Reperfusion; Stents; Thrombectomy; Treatment Outcome
PubMed: 34581737
DOI: 10.1001/jama.2021.13827 -
Kidney International Oct 2023Ischemia-reperfusion (IR) injury, a leading cause of acute kidney injury (AKI), is still without effective therapies. Succinate accumulation during ischemia followed by...
Inhibition of pyruvate dehydrogenase kinase 4 ameliorates kidney ischemia-reperfusion injury by reducing succinate accumulation during ischemia and preserving mitochondrial function during reperfusion.
Ischemia-reperfusion (IR) injury, a leading cause of acute kidney injury (AKI), is still without effective therapies. Succinate accumulation during ischemia followed by its oxidation during reperfusion leads to excessive reactive oxygen species (ROS) and severe kidney damage. Consequently, the targeting of succinate accumulation may represent a rational approach to the prevention of IR-induced kidney injury. Since ROS are generated primarily in mitochondria, which are abundant in the proximal tubule of the kidney, we explored the role of pyruvate dehydrogenase kinase 4 (PDK4), a mitochondrial enzyme, in IR-induced kidney injury using proximal tubule cell-specific Pdk4 knockout (Pdk4) mice. Knockout or pharmacological inhibition of PDK4 ameliorated IR-induced kidney damage. Succinate accumulation during ischemia, which is responsible for mitochondrial ROS production during reperfusion, was reduced by PDK4 inhibition. PDK4 deficiency established conditions prior to ischemia resulting in less succinate accumulation, possibly because of a reduction in electron flow reversal in complex II, which provides electrons for the reduction of fumarate to succinate by succinate dehydrogenase during ischemia. The administration of dimethyl succinate, a cell-permeable form of succinate, attenuated the beneficial effects of PDK4 deficiency, suggesting that the kidney-protective effect is succinate-dependent. Finally, genetic or pharmacological inhibition of PDK4 prevented IR-induced mitochondrial damage in mice and normalized mitochondrial function in an in vitro model of IR injury. Thus, inhibition of PDK4 represents a novel means of preventing IR-induced kidney injury, and involves the inhibition of ROS-induced kidney toxicity through reduction in succinate accumulation and mitochondrial dysfunction.
Topics: Mice; Animals; Succinic Acid; Reactive Oxygen Species; Mice, Knockout; Reperfusion Injury; Ischemia; Kidney; Mitochondria; Reperfusion
PubMed: 37399974
DOI: 10.1016/j.kint.2023.06.022 -
Stroke and Vascular Neurology Feb 2024Recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) was not inferior to alteplase for ischaemic stroke within 4.5 hours. Our study aimed to investigate... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND PURPOSE
Recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) was not inferior to alteplase for ischaemic stroke within 4.5 hours. Our study aimed to investigate the efficacy and safety of rhTNK-tPA in patients who had an ischaemic stroke due to large vessel occlusion (LVO) of anterior circulation beyond 4.5 hours.
METHODS AND DESIGN
Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-III (TRACE III) is a multicentre, prospective, randomised, open-label, blind endpoint, controlled clinical trial. Patients who had an ischaemic stroke due to anterior circulation LVO (internal carotid artery, middle cerebral artery M1 and M2 segments) within 4.5-24 hours from last known well (including wake-up stroke and no witness stroke) and with salvageable tissue (ischaemic core volume <70 mL, mismatch ratio ≥1.8 and mismatch volume ≥15 mL) based on CT perfusion or MRI perfusion-weighted imaging (PWI) were included and randomised to rhTNK-tPA 0.25 mg/kg (single bolus) to a maximum of 25 mg or standard medical therapy. Specially, we will exclude patients who are intended for direct thrombectomy. All will be followed up for 90 days.
STUDY OUTCOMES
Primary efficacy outcome is modified Rankin Scale (mRS) score ≤1 at 90 days. Secondary efficacy outcomes include ordinal distribution of mRS at 90 days, major neurological improvement defined by a decrease ≥8 points compared with the initial deficit or a score ≤1 on the National Institutes of Health Stroke Scale (NIHSS) at 72 hours, mRS score ≤2 at 90 days, the rate of improvement on Tmax >6 s at 24 hours and NIHSS score change from baseline at 7 days. Safety outcomes are symptomatic intracerebral haemorrhage within 36 hours and mortality at 90 days.
DISCUSSION
TRACE III will provide evidence for the efficacy and safety of rhTNK-tPA in patients who had an ischaemic strokes due to anterior circulation LVO beyond 4.5 hours.
TRIAL REGISTRATION NUMBER
NCT05141305.
Topics: United States; Humans; Tenecteplase; Fibrinolytic Agents; Stroke; Brain Ischemia; Prospective Studies; Treatment Outcome; Ischemic Stroke; Reperfusion
PubMed: 37247876
DOI: 10.1136/svn-2023-002310