OBJECTIVETo assess the frequency and utilization trends of dabigatran reversal with idarucizumab and compare associated complications, outcomes, and door-to-needle times to those of patients not ...exposed to idarucizumab in a nationwide cohort of thrombolyzed patients over a 24-month period.
METHODSThis is an observational cohort study of all New Zealand patients with stroke treated with stroke reperfusion entered into a mandatory online national registry. Each hospital records data including patient demographics, treatment delays, complications, 7-day outcomes, and idarucizumab use.
RESULTSBetween 1 January 2017 and 31 December 2018, 1,336 patients received thrombolysis. Fifty-one patients received idarucizumab prior to thrombolysis (median interquartile range age 73 57–83 years)8 (1.3%) in 2017 and 43 (6%) in 2018 (p < 0.001). Over the same 24-month period, 386 patients had stroke clot retrieval, of whom 8 (2.1%) were first treated with idarucizumab. Idarucizumab-treated patients had slower door-to-needle times (83 54–110 minutes vs 61 43–85 minutes, p = 0.0006). Symptomatic intracerebral hemorrhage occurred in 2 (3.9%) of the idarucizumab-treated patients and 49 (3.8%) of the other thrombolyzed patients (p = 0.97). None of the idarucizumab-treated patients had significant thrombotic complications. At 7 days, 3 (5.9%) idarucizumab-treated and 101 (7.9%) of the other thrombolyzed patients had died (p = 0.61).
CONCLUSIONIdarucizumab was used in 6% of all thrombolyzed patients in a national cohort during 2018, up from 1.3% in 2017. Idarucizumab appeared to be safe with similar clinical outcomes to routinely managed patients, despite a 22-minute door-to-needle time delay. Idarucizumab can facilitate thrombolysis in patients with stroke taking dabigatran.
CLASSIFICATION OF EVIDENCEThis study provides Class III evidence that idarucizumab use is associated with similar early post-thrombolysis outcomes compared with patients not exposed to this drug.
In ischemic stroke, intravenous tenecteplase is noninferior to alteplase in selected patients and has some practical advantages. Several stroke centers in New Zealand changed to routine off-label ...intravenous tenecteplase due to improved early recanalization in large vessel occlusion, inconsistent access to thrombectomy within stroke networks, and for consistency in treatment protocols between patients with and without large vessel occlusion. We report the feasibility and safety outcomes in tenecteplase-treated patients.
We performed a retrospective analysis of consecutive patients thrombolyzed with intravenous tenecteplase at 1 comprehensive and 2 regional stroke centers from July 14, 2018, to February 29, 2020. We report the baseline clinical characteristics, rates of symptomatic intracranial hemorrhage, and angioedema. These were then compared with patient outcomes with those treated with intravenous alteplase at 2 other comprehensive stroke centers. Multivariable mixed-effects logistic regression models were performed assessing the association of tenecteplase with symptomatic intracranial hemorrhage and independent outcome (modified Rankin Scale score, 0-2) at day 90.
There were 165 patients treated with tenecteplase and 254 with alteplase. Age (75 versus 74 years), sex (56% versus 60% male), National Institutes of Health Stroke Scale scores (8 versus 10), median door-to-needle times (47 versus 48 minutes), or onset-to-needle time (129 versus 130 minutes) were similar between the groups. Symptomatic intracranial hemorrhage occurred in 3 (1.8% 95% CI, 0.4-5.3) tenecteplase patients compared with 7 (2.7% 95% CI, 1.1-5.7) alteplase patients (
=0.75). There were no differences between tenecteplase and alteplase in the rates of angioedema (4 2.4%; 95% CI, 0.7-6.2 versus 1 0.4%; 95% CI, 0.01-2.2,
=0.08) or 90-day functional independence (100 61% versus 140 57%,
=0.47), respectively. In mixed-effects logistic regression models, there was no significant association between thrombolytic choice and symptomatic intracranial hemorrhage (odds ratio tenecteplase, 0.62 95% CI, 0.14-2.80,
=0.53) or functional independence (odds ratio tenecteplase, 1.20 95% CI, 0.74-1.95,
=0.46).
Routine use of tenecteplase for stroke thrombolysis was feasible and had comparable safety profile and outcome to alteplase.
Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS) is a recently recognized neurodegenerative disease with onset in mid- to late adulthood. The genetic basis for a ...large proportion of Caucasian patients was recently shown to be the biallelic expansion of a pentanucleotide (AAGGG)n repeat in RFC1. Here, we describe the first instance of CANVAS genetic testing in New Zealand Māori and Cook Island Māori individuals. We show a novel, possibly population-specific CANVAS configuration (AAAGG)10-25(AAGGG)exp, which was the cause of CANVAS in all patients. There were no apparent phenotypic differences compared with European CANVAS patients. Presence of a common disease haplotype among this cohort suggests this novel repeat expansion configuration is a founder effect in this population, which may indicate that CANVAS will be especially prevalent in this group. Haplotype dating estimated the most recent common ancestor at ∼1430 ce. We also show the same core haplotype as previously described, supporting a single origin of the CANVAS mutation.
In a trial involving patients with large acute strokes, endovascular thrombectomy resulted in better functional outcomes than medical care alone but was associated with vascular complications.
Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a progressive late-onset, neurological disease. Recently, a pentanucleotide expansion in intron 2 of RFC1 was identified as ...the genetic cause of CANVAS. We screened an Asian-Pacific cohort for CANVAS and identified a novel RFC1 repeat expansion motif, (ACAGG)exp, in three affected individuals. This motif was associated with additional clinical features including fasciculations and elevated serum creatine kinase. These features have not previously been described in individuals with genetically-confirmed CANVAS. Haplotype analysis showed our patients shared the same core haplotype as previously published, supporting the possibility of a single origin of the RFC1 disease allele. We analysed data from >26 000 genetically diverse individuals in gnomAD to show enrichment of (ACAGG) in non-European populations.
Direct oral anticoagulants (DOACs) have emerged as primary therapeutic option for stroke prevention in patients with atrial fibrillation. However, patients may have ischaemic stroke despite DOAC ...therapy and there is uncertainty whether those patients can safely receive intravenous thrombolysis or mechanical thrombectomy. In this review, we summarise and discuss current knowledge about different approaches to select patient. Time since last DOAC intake-as a surrogate for anticoagulant activity-is easy to use but limited by interindividual variability of drug pharmacokinetics and long cut-offs (>48 hours). Measuring anticoagulant activity using drug-specific coagulation assays showed promising safety results. Large proportion of patients at low anticoagulant activity seem to be potentially treatable but there remains uncertainty about exact safe cut-off values and limited assay availability. The use of specific reversal agents (ie, idarucizumab or andexanet alfa) prior to thrombolysis is a new emerging option with first data reporting safety but issues including health economics need to be elucidated. Mechanical thrombectomy appears to be safe without any specific selection criteria applied. In patients on DOAC therapy with large vessel occlusion, decision for intravenous thrombolysis should not delay thrombectomy (eg, direct thrombectomy or immediate transfer to a thrombectomy-capable centre recommended). Precision medicine using a tailored approach combining clinicoradiological information (ie, penumbra and vessel status), anticoagulant activity and use of specific reversal agents only if necessary seems a reasonable choice.
In a randomized trial involving patients with acute stroke, the incidence of revascularization was higher with tenecteplase than with alteplase for intravenous thrombolysis before endovascular ...thrombectomy. Cerebral hemorrhage occurred at the same rate in each group.
Purpose of Review
When compared to ischaemic stroke, there have been limited advances in acute management of intracerebral haemorrhage. Blood pressure control in the acute period is an intervention ...commonly implemented and recommended in guidelines, as elevated systolic blood pressure is common and associated with haematoma expansion, poor functional outcomes, and mortality. This review addresses the uncertainty around the optimal blood pressure intervention, specifically timing and length of intervention, intensity of blood pressure reduction and agent used.
Recent Findings
Recent pivotal trials have shown that acute blood pressure intervention, to a systolic target of 140mmHg, does appear to be beneficial in ICH, particularly when bundled with other therapies such as neurosurgery in selected cases, access to critical care units, blood glucose control, temperature management and reversal of coagulopathy.
Summary
Systolic blood pressure should be lowered acutely in intracerebral haemorrhage to a target of approximately 140mmHg, and that this intervention is generally safe in the ICH population.
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