External validation of the SEDAN score for prediction of intracerebral hemorrhage in stroke thrombolysis

The SEDAN score is a prediction rule for assessment of the risk of symptomatic intracerebral hemorrhage (SICH) per the European Cooperative Acute Stroke Study (ECASS) II definition in patients with acute ischemic stroke treated with intravenous thrombolysis. We assessed the performance of the score in predicting SICH per the ECASS II and Safe Implementation of Treatments in Stroke Monitoring Study (SITS-MOST) definitions in the SITS\u2013International Stroke Thrombolysis Register (SITS-ISTR). Methods\u2014We calculated the SEDAN score in 34 251 patients with complete data, enrolled into the SITS-ISTR. The risk for SICH by both definitions was calculated per score category. Odds ratios for SICH per point increase of the score were obtained using logistic regression. The predictive performance was assessed using area under the curve of the receiver operating characteristic (AUC-ROC). Results\u2014The predictive capability for SICH per ECASS II was moderate at AUC-ROC=0.66. With rising scores, there was a moderate increase in risk for SICH per ECASS II (odds ratio, 1.65 per point; 95% confidence interval, 1.59\u20131.72; P<0.001), with SICH rates between 1.6% for 0 points and 16.9% for 655 points, average 5.1%. The predictive capability for SICH per SITS\u2013MOST was weaker, AUC-ROC=0.60, with lower increase per score point (odds ratio, 1.36 per point; 95% confidence interval, 1.28\u20131.46; P<0.001), and SICH rates between 0.8% for 0 points and 5.4% for 655 points, average 1.8%. Conclusions\u2014In this very large data set, the predictive and discriminatory performances of the SEDAN score were only moderate for SICH per ECASS II and low for SICH per SITS\u2013Monitoring Study

The role of colchicine in the prevention of cerebrovascular ischemia

Introduction: Despite the proven efficacy of anti-thrombotic, lipid-lowering, anti-hypertensive therapies and lifestyle modification changes for secondary ischemic stroke prevention, the risk of recurrent stroke, coronary events and vascular death remains substantial even for patients treated with high rates of established secondary preventive medications. Methods: In the present review, we summarize available literature data on the association between systemic inflammation and symptomatic atherosclerosis including recurrent cerebral ischemia. We also highlight the potential role of colchicine in the suppression of atherosclerosis-induced inflammation, plaque stabilization and thromboembolism prevention. Results: Accumulating evidence suggests that inflammation is of key importance in the pathophysiology of atherosclerotic plaque de-stabilization and thromboembolism, with inflammatory cells being involved in all stages of atherosclerosis development. Therefore, anti-inflammatory therapies targeting the atherosclerotic plaque inflammation may be important contributors in plaque stabilization and in the prevention of thromboembolic events. Colchicine is known to have multiple anti-inflammatory properties including inhibition of microtubule polymerization, leading to reduced secretion in monocyte-macrophages. Currently the randomized controlled CONVINCE trial is enrolling stroke patients to evaluate the effect of a daily low-dose of colchicine in reducing the rate of recurrent stroke and major vascular events. Conclusion: Inflammatory pathways seem to be key mediators in the development of atherosclerotic process, atheromatous plaque destabilization and thromboembolism. Colchicine as a novel therapeutic agent could be a safe and effective inhibitor of the inflammation cascade in patients with extra-or intracranial atherosclerosis or arteriolosclerosis, resulting in reduced vascular events. © 2017 Bentham Science Publishers

Safety of Statin Pretreatment in Intravenous Thrombolysis for Acute Ischemic Stroke

Background and Purpose - A recent meta-analysis investigating the association between statins and early outcomes in acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT) indicated that prestroke statin treatment was associated with increased risk of 90-day mortality and symptomatic intracranial hemorrhage. We investigated the potential association of statin pretreatment with early outcomes in a large, international registry of AIS patients treated with IVT. Methods - We analyzed prospectively collected data from the Safe Implementation of Treatments in Stroke-East registry (SITS-EAST) registry on consecutive AIS patients treated with IVT during an 8-year period. Early clinical recovery within 24 hours was defined as reduction in baseline National Institutes of Health Stroke Scale score of ≥10 points. Favorable functional outcome at 3 months was defined as modified Rankin Scale scores of 0 to 1. Symptomatic intracranial hemorrhage was diagnosed using National Institute of Neurological Disorders and Stroke, European-Australasian Acute Stroke Study-II and SITS definitions. Results - A total of 1660 AIS patients treated with IVT fulfilled our inclusion criteria. Patients with statin pretreatment (23%) had higher baseline stroke severity compared with cases who had not received any statin at symptom onset. After adjusting for potential confounders, statin pretreatment was not associated with a higher likelihood of symptomatic intracranial hemorrhage defined by any of the 3 definitions. Statin pretreatment was not related to 3-month all-cause mortality (odds ratio, 0.92; 95% confidence interval, 0.57-1.49; P=0.741) or 3-month favorable functional outcome (odds ratio, 0.81; 95% confidence interval, 0.52-1.27; P=0.364). Statin pretreatment was independently associated with a higher odds of early clinical recovery (odds ratio, 1.91; 95% confidence interval, 1.25-2.92; P=0.003). Conclusions - Statin pretreatment seems not to be associated with adverse outcomes in AIS patients treated with IVT. The effect of statin pretreatment on early functional outcomes in thrombolysed AIS patients deserves further investigation. © 2015 American Heart Association, Inc

Intravenous thrombolysis for patients with in-hospital stroke onset: propensity-matched analysis from the Safe Implementation of Treatments in Stroke-East registry

Background and purpose: Recent cross-sectional study data suggest that intravenous thrombolysis (IVT) in patients with in-hospital stroke (IHS) onset is associated with unfavorable functional outcomes at hospital discharge and in-hospital mortality compared to patients with out-of-hospital stroke (OHS) onset treated with IVT. We sought to compare outcomes between IVT-treated patients with IHS and OHS by analysing propensity-score-matched data from the Safe Implementation of Treatments in Stroke-East registry. Methods: We compared the following outcomes for all propensity-score-matched patients: (i) symptomatic intracranial hemorrhage defined with the safe implementation of thrombolysis in stroke-monitoring study criteria, (ii) favorable functional outcome defined as a modified Rankin Scale (mRS) score of 0–1 at 3 months, (iii) functional independence defined as an mRS score of 0–2 at 3 months and (iv) 3-month mortality. Results: Out of a total of 19 077 IVT-treated patients with acute ischaemic stroke, 196 patients with IHS were matched to 5124 patients with OHS, with no differences in all baseline characteristics (P &gt; 0.1). Patients with IHS had longer door-to-needle [90 (interquartile range, IQR, 60–140) vs. 65 (IQR, 47–95) min, P &lt; 0.001] and door-to-imaging [40 (IQR, 20–90) vs. 24 (IQR, 15–35) min, P &lt; 0.001] times compared with patients with OHS. No differences were detected in the rates of symptomatic intracranial hemorrhage (1.6% vs. 1.9%, P = 0.756), favorable functional outcome (46.4% vs. 42.3%, P = 0.257), functional independence (60.7% vs. 60.0%, P = 0.447) and mortality (14.3% vs. 15.1%, P = 0.764). The distribution of 3-month mRS scores was similar in the two groups (P = 0.273). Conclusions: Our findings underline the safety and efficacy of IVT for IHS. They also underscore the potential of reducing in-hospital delays for timely tissue plasminogen activator delivery in patients with IHS. © 2017 EA

Intravenous thrombolysis for ischemic stroke in the golden hour: propensity-matched analysis from the SITS-EAST registry

As there are scarce data regarding the outcomes of acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT) within 60 min from symptom onset (“golden hour”), we sought to compare outcomes between AIS patients treated within [GH(+)] and outside [GH(−)] the “golden hour” by analyzing propensity score matched data from the SITS-EAST registry. Clinical recovery (CR) at 2 and 24 h was defined as a reduction of ≥10 points on NIHSS-score or a total NIHSS-score of ≤3 at 2 and 24 h, respectively. A relative reduction in NIHSS-score of ≥40% at 2 h was considered predictive of complete recanalization (CREC). Symptomatic intracranial hemorrhage (sICH) was defined using SITS-MOST criteria. Favorable functional outcome (FFO) was defined as a mRS-score of 0–1 at 3 months. Out of 19,077 IVT-treated AIS patients, 71 GH(+) patients were matched to 6882 GH(−) patients, with no differences in baseline characteristics (p &gt; 0.1). GH(+) had higher rates of CR at 2 (31.0 vs. 12.4%; p &lt; 0.001) and 24 h (41 vs. 27%; p = 0.010), CREC at 2 h (39 vs. 21%; p &lt; 0.001) and FFO (46.5 vs. 34.0%; p = 0.028) at 3 months. The rates of sICH and 3-month mortality did not differ (p &gt; 0.2) between the two groups. GH(+) was associated with 2-h CR (OR: 5.34; 95% CI 2.53–11.03) and CREC (OR: 2.38; 95% CI 1.38–4.09), 24-h CR (OR: 1.88; 95% CI 1.08–3.26) and 3-month FFO (OR: 2.02; 95% CI 1.15–3.54) in multivariable logistic regression models adjusting for potential confounders. In conclusion, AIS treated with IVT within the GH seems to have substantially higher odds of early neurological recovery, CREC, 3-month FFO and functional improvement. © 2017, Springer-Verlag Berlin Heidelberg

The angiotensin-receptor blocker candesartan for treatment of acute stroke (SCAST): a randomised, placebo-controlled, double-blind trial.

South-Eastern Norway Regional Health Authority; Oslo University Hospital Ullevål; AstraZeneca; Takeda

Regulation and governance of multinational drug trials in stroke : Barriers and possibilities

Over the last 10 years, there has been stagnation in the number of multinational drug trials in stroke in Europe. One important cause of this is probably the increased burden of laws and regulations that came with the European Union Clinical Trials Directive. The main objective of research regulation and governance should be to protect research participants, their tissues, and data, but the approval systems are complex, regulation is variably interpreted and enforced, and the assessment of studies is often not proportionate to the risk of the research to participants. Such unnecessary barriers should be reduced by simplifying, centralizing, and harmonizing the application process, and by applying regulatory and governance requirements in a way that is proportionate to the potential harms to the patients. The traditional functions of a regulator (in setting, monitoring, and enforcing quality standards) could also be supplemented with an aim to actively help researchers achieve these standards, for example, by giving advice, and ultimately with an aim to facilitate and promote research, for example, by integrating research in everyday clinical practice. Research networks offer one way of integrating research and clinical practice across multiple centers, and can streamline research delivery by supporting researchers deal professionally and efficiently with the regulations and governance requirements. © 2015 World Stroke Organization