Recent advances in cardiovascular medicines : thrombolytics

Thrombolytic therapy represents a major advance in reducing mortality following myocardial infarction. Pharmacists must be aware of the principles and problems of thrombolysis and the extant large studies conducted in hospitals and in the community. This article describes the various use and medicinal aspects of the various thrombolytic agents available on the market.peer-reviewe

EFFICACY AND SAFETY OF LOW-DOSE VERSUS STANDARD-DOSE ALTEPLASE REGIMENS IN PATIENTS WITH ACUTE ISCHAEMIC STROKE

Background: The use of intravenous recombinant tissue plasminogen activator, alteplase, at a dose of 0.9 mg/kg is an effective treatment for patients with acute ischaemic stroke; this dose is also associated with high intracerebral haemorrhage rates. The aim of this study was to evaluate whether the low-dose alteplase treatment is as effective and safe as the standard-dose regimen. Subjects and methods: This was a retrospective, single-centre study, and data were collected from the Hospital Stroke Registry. Based on the severity of stroke and the risk of intracerebral haemorrhage, patients were divided into two groups according to the alteplase doses given; the low-dose (0.6 mg/kg) group (n=45) and the standard-dose (0.9 mg/kg) group (n=165). Ninety-day outcomes measured as modified Rankin score and National Institute for Health Stroke Scale (NIHSS) score, as well as symptomatic intracerebral haemorrhage and mortality rates were analysed. Results: The standard-dose group had a slightly more favourable outcome (Rankin score 0-2) at 90 days after alteplase treatment than the low-dose group (64.24% vs. 53.33%), but the difference was not significant. The total intracerebral haemorrhage rate and mortality rate at 90 days were higher in the standard-dose group than in the low-dose group (21.2% vs. 13.3% and 6.1% vs. 0.0%, respectively), but these differences were not statistically significant. Conclusion: The low-dose alteplase treatment applied to the patients with high intracerebral haemorrhage risk had comparable efficacy and safety profile to the standard-dose regimen

EFFICACY AND SAFETY OF LOW-DOSE VERSUS STANDARD-DOSE ALTEPLASE REGIMENS IN PATIENTS WITH ACUTE ISCHAEMIC STROKE

Background: The use of intravenous recombinant tissue plasminogen activator, alteplase, at a dose of 0.9 mg/kg is an effective treatment for patients with acute ischaemic stroke; this dose is also associated with high intracerebral haemorrhage rates. The aim of this study was to evaluate whether the low-dose alteplase treatment is as effective and safe as the standard-dose regimen. Subjects and methods: This was a retrospective, single-centre study, and data were collected from the Hospital Stroke Registry. Based on the severity of stroke and the risk of intracerebral haemorrhage, patients were divided into two groups according to the alteplase doses given; the low-dose (0.6 mg/kg) group (n=45) and the standard-dose (0.9 mg/kg) group (n=165). Ninety-day outcomes measured as modified Rankin score and National Institute for Health Stroke Scale (NIHSS) score, as well as symptomatic intracerebral haemorrhage and mortality rates were analysed. Results: The standard-dose group had a slightly more favourable outcome (Rankin score 0-2) at 90 days after alteplase treatment than the low-dose group (64.24% vs. 53.33%), but the difference was not significant. The total intracerebral haemorrhage rate and mortality rate at 90 days were higher in the standard-dose group than in the low-dose group (21.2% vs. 13.3% and 6.1% vs. 0.0%, respectively), but these differences were not statistically significant. Conclusion: The low-dose alteplase treatment applied to the patients with high intracerebral haemorrhage risk had comparable efficacy and safety profile to the standard-dose regimen

Phase I and Phase II Therapies for Acute Ischemic Stroke: An Update on Currently Studied Drugs in Clinical Research.

Acute ischemic stroke is a devastating cause of death and disability, consequences of which depend on the time from ischemia onset to treatment, the affected brain region, and its size. The main targets of ischemic stroke therapy aim to restore tissue perfusion in the ischemic penumbra in order to decrease the total infarct area by maintaining blood flow. Advances in research of pathological process and pathways during acute ischemia have resulted in improvement of new treatment strategies apart from restoring perfusion. Additionally, limiting the injury severity by manipulating the molecular mechanisms during ischemia has become a promising approach, especially in animal research. The purpose of this article is to review completed and ongoing phases I and II trials for the treatment of acute ischemic stroke, reviewing studies on antithrombotic, thrombolytic, neuroprotective, and antineuroinflammatory drugs that may translate into more effective treatments

Low-dose versus standard-dose alteplase in acute ischemic stroke in Asian stroke registries: an individual patient data pooling study

10.1177/1747493019858777INTERNATIONAL JOURNAL OF STROKE147670-67

Cerebrovascular disease - Advances in management

Recent advances in the diagnosis and treatment of stroke have justified its management as a medical emergency. This article summarises current recommendations for the initial management of major types of stroke with emphasis on acute therapy for ischaemic stroke. Recommendations are based on the results of well-designed clinical trials. An acute stroke care team and an acute stroke unit should be established in all regional hospitals. Diagnosis of stroke must be accurate. General management aims for prevention and treatment of neurological and systemic complications, whereas specific management varies according to the stroke type and the underlying pathogenic mechanisms. For selected patients with ischaemic stroke, intravenous recombinant tissue plasminogen activator or a modified viper venom within 3 hours of onset, or intra-arterial pro-urokinase within 6 hours may improve functional outcomes. Neuro-surgical treatment is indicated for some patients with ischaemic or haemorrhagic strokes. Prevention of recurrence and rehabilitation are the core components of subsequent management.published_or_final_versio

Endogenous Fibrinolysis : An Important Mediator of Thrombus Formation and Cardiovascular Risk

© 2015 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION. PUBLISHED BY ELSEVIER INC.Most acute cardiovascular events are attributable to arterial thrombosis. Plaque rupture or erosion stimulates platelet activation, aggregation, and thrombosis, whilst simultaneously activating enzymatic processes that mediate endogenous fibrinolysis to physiologically maintain vessel patency. Interplay between these pathways determines clinical outcome. If proaggregatory factors predominate, the thrombus may propagate, leading to vessel occlusion. However, if balanced by a healthy fibrinolytic system, thrombosis may not occur or cause lasting occlusion. Despite abundant evidence for the fibrinolytic system regulating thrombosis, it has been overlooked compared with platelet reactivity, partly due to a lack of techniques to measure it. We evaluate evidence for endogenous fibrinolysis in arterial thrombosis and review techniques to assess it, including biomarkers and global assays, such as thromboelastography and the Global Thrombosis Test. Global assays, simultaneously assessing proaggregatory and fibrinolytic pathways, could play a role in risk stratification and in identifying impaired fibrinolysis as a potential target for pharmacological modulation.Peer reviewedFinal Published versio

Editor's choice : European Society for Vascular Surgery (ESVS) 2020 clinical practice guidelines on the management of acute limb ischaemia

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Development and Testing of Thrombolytics in Stroke

Despite recent advances in recanalization therapy, mechanical thrombectomy will never be a treatment for every ischemic stroke because access to mechanical thrombectomy is still limited in many countries. Moreover, many ischemic strokes are caused by occlusion of cerebral arteries that cannot be reached by intra-arterial catheters. Reperfusion using thrombolytic agents will therefore remain an important therapy for hyperacute ischemic stroke. However, thrombolytic drugs have shown limited efficacy and notable hemorrhagic complication rates, leaving room for improvement. A comprehensive understanding of basic and clinical research pipelines as well as the current status of thrombolytic therapy will help facilitate the development of new thrombolytics. Compared with alteplase, an ideal thrombolytic agent is expected to provide faster reperfusion in more patients; prevent re-occlusions; have higher fibrin specificity for selective activation of clot-bound plasminogen to decrease bleeding complications; be retained in the blood for a longer time to minimize dosage and allow administration as a single bolus; be more resistant to inhibitors; and be less antigenic for repetitive usage. Here, we review the currently available thrombolytics, strategies for the development of new clot-dissolving substances, and the assessment of thrombolytic efficacies in vitro and in vivo