Dataset Information

Thrombolysis in Stroke within 30 Minutes: Results of the Acute Brain Care Intervention Study.

ABSTRACT:

Background and purpose

Time is brain: benefits of intravenous thrombolysis (IVT) in ischemic stroke last for 4.5 hours but rapidly decrease as time progresses following symptom onset. The goal of the Acute Brain Care (ABC) intervention study was to reduce the door-to-needle time (DNT) to ≤30 minutes by optimizing in-hospital stroke treatment.

Methods

We performed a single-centre before (pre-intervention period: 2000-2005) versus after (post-intervention period: 2006-2012) comparison in a cohort of consecutive patients treated with IVT. The intervention consisted of the implementation of a multidisciplinary stroke protocol combining simple strategies to reduce the DNT. Primary endpoint was the DNT, presented as proportion ≤30 minutes and median time. Secondary clinical endpoints were symptomatic intracranial hemorrhage (SICH), and favourable outcome defined as a modified Rankin scale (mRs) score of 0-2 at 3 months. Endpoints were additionally adjusted for baseline imbalances between the groups.

Results

In the pre-intervention period, none (0.0%) of the 100 patients (mean age 63.8 years, median National Institutes of Health Stroke Scale [NIHSS] score 14) treated with IVT had a DNT ≤30 minutes compared to 234 (62.7%) of the 373 patients (mean age 66.7 years, median NIHSS score 10) in the post-intervention period (p<0.001). The median DNT decreased from 75 (IQR 60-105) to 28 minutes (IQR 20-37, p<0.001). SICH rate remained stable (3.0% versus 4.4%, OR 1.50, 95% CI 0.43─5.25; adjusted OR 5.47, 95% CI 0.69-42.12). The proportion of patients with a favourable outcome increased (38.9% versus 52.3%, OR 1.72, 95% CI 1.09-2.73) but lost statistical significance after adjustment (adjusted OR 1.46, 95% CI 0.82-2.61).

Conclusions

Important and sustained reduction of the DNT to 30 minutes or less can be safely achieved by optimizing in-hospital stroke treatment. With its simple strategies, the ABC-protocol is a pragmatic framework for increasing the therapeutic yield in time-dependent stroke treatment.

SUBMITTER: Zinkstok SM

PROVIDER: S-EPMC5115772 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Tenecteplase is a fibrinolytic drug with higher fibrin specificity and longer half-life than the standard stroke thrombolytic, alteplase, permitting the convenience of single bolus administration. Tenecteplase, at 0.5 mg/kg, has regulatory approval to treat ST-segment-elevation myocardial infarction, for which it has equivalent 30-day mortality and fewer systemic hemorrhages. Investigated as a thrombolytic for ischemic stroke over the past 15 years, tenecteplase is currently being studied in several phase 3 trials. Based on a systematic literature search, we provide a qualitative synthesis of published stroke clinical trials of tenecteplase that (1) performed randomized comparisons with alteplase, (2) compared different doses of tenecteplase, or (3) provided unique quantitative meta-analyses. Four phase 2 and one phase 3 study performed randomized comparisons with alteplase. These and other phase 2 studies compared different tenecteplase doses and effects on early outcomes of recanalization, reperfusion, and substantial neurological improvement, as well as symptomatic intracranial hemorrhage and 3-month disability on the modified Rankin Scale. Although no single trial prospectively demonstrated superiority or noninferiority of tenecteplase on clinical outcome, meta-analyses of these trials (1585 patients randomized) point to tenecteplase superiority in recanalization of large vessel occlusions and noninferiority in disability-free 3-month outcome, without increases in symptomatic intracranial hemorrhage or mortality. Doses of 0.25 and 0.4 mg/kg have been tested, but no advantage of the higher dose has been suggested by the results. Current clinical practice guidelines for stroke include intravenous tenecteplase at either dose as a second-tier option, with the 0.25 mg/kg dose recommended for large vessel occlusions, based on a phase 2 trial that demonstrated superior recanalization and improved 3-month outcome relative to alteplase. Ongoing randomized phase 3 trials may better define the comparative risks and benefits of tenecteplase and alteplase for stroke thrombolysis and answer questions of tenecteplase efficacy in the >4.5-hour time window, in wake-up stroke, and in combination with endovascular thrombectomy.

Project description:Thrombolysis using intravenous (IV) tissue plasminogen activator (tPA) is one of few evidence-based acute stroke treatments, yet achieving high rates of IV tPA delivery has been problematic. The 4.5-h treatment window, the complexity of determining eligibility criteria and the availability of expertise and required resources may impact on treatment rates, with barriers encountered at the levels of the individual clinician, the social context and the health system itself. The review aimed to describe health system factors associated with higher rates of IV tPA administration for ischemic stroke and to identify whether system-focussed interventions increased tPA rates for ischemic stroke.Published original English-language research from four electronic databases spanning 1997-2014 was examined. Observational studies of the association between health system factors and tPA rates were described separately from studies of system-focussed intervention strategies aiming to increase tPA rates. Where study outcomes were sufficiently similar, a pooled meta-analysis of outcomes was conducted.Forty-one articles met the inclusion criteria: 7 were methodologically rigorous interventions that met the Cochrane Collaboration Evidence for Practice and Organization of Care (EPOC) study design guidelines and 34 described observed associations between health system factors and rates of IV tPA. System-related factors generally associated with higher IV tPA rates were as follows: urban location, centralised or hub and spoke models, treatment by a neurologist/stroke nurse, in a neurology department/stroke unit or teaching hospital, being admitted by ambulance or mobile team and stroke-specific protocols. Results of the intervention studies suggest that telemedicine approaches did not consistently increase IV tPA rates. Quality improvement strategies appear able to provide modest increases in stroke thrombolysis (pooled odds ratio = 2.1, p = 0.05).In order to improve IV tPA rates in acute stroke care, specific health system factors need to be targeted. Multi-component quality improvement approaches can improve IV tPA rates for stroke, although more thoughtfully designed and well-reported trials are required to safely increase rates of IV tPA to eligible stroke patients.

Project description:Background and purposeRecent studies have shown that several proteins, including Axl, are related to hemorrhagic transformation (HT) following intravenous thrombolysis by affecting blood-brain barrier (BBB) function. However, the effects of these proteins on BBB function have been studied primarily in animal models. In this study, we aimed to identify serum protein markers that predict HT following intravenous thrombolysis in patients with acute ischemic stroke (AIS) and verify whether these serum proteins regulate BBB function and HT in animal stroke models.MethodsFirst, 118 AIS patients were enrolled in this study, including 52 HT patients and 66 non-HT patients. In Step 1, baseline serum levels of Axl, angiopoietin-like 4, C-reactive protein, ferritin, hypoxia-inducible factor-1 alpha, HTRA2, Lipocalin2, matrix metallopeptidase 9, platelet-derived growth factor-BB, and tumor necrosis factor alpha were measured using a quantitative cytokine chip. Next, sequence mutations and variations in genes encoding the differentially expressed proteins identified in Step 1 and subsequent function-related proteins were detected. Finally, we verified whether manipulation of differentially expressed proteins affected BBB function and HT in a hyperglycemia-induced rat stroke model.ResultsSerum Axl levels were significantly lower in the HT group than in the non-HT group; none of the other protein markers differed significantly between the two groups. Genetic testing revealed that sequence variations of GAS6 (the gene encoding the Axl ligand)-derived long non-coding RNA, GAS6-AS1, were significantly correlated with an increased risk of HT after intravenous thrombolysis. In animal studies, administration of recombinant GAS6 significantly reduced brain infarction and neurological deficits and attenuated BBB disruption and HT.ConclusionsLower serum Axl levels, which may result from sequence variations in GAS6-AS1, are correlated with an increased risk of HT after intravenous thrombolysis in stroke patients. Activation of the Axl signaling pathway by the GAS6 protein may serve as a therapeutic strategy to reduce HT in AIS patients.