-
1.
Cilostazol Versus Aspirin in Ischemic Stroke Patients With High-Risk Cerebral Hemorrhage: Subgroup Analysis of the PICASSO Trial.
Kim, BJ, Kwon, SU, Park, JH, Kim, YJ, Hong, KS, Wong, LKS, Yu, S, Hwang, YH, Lee, JS, Lee, J, et al
Stroke. 2020;(3):931-937
Abstract
Background and Purpose- Although cilostazol has shown less hemorrhagic events than aspirin, only marginal difference was observed in hemorrhagic stroke events among patients at high risk for cerebral hemorrhage. To identify patients who would most benefit from cilostazol, this study analyzed interactions between treatment and subgroups of the PICASSO trial (Prevention of Cardiovascular Events in Asian Ischemic Stroke Patients With High Risk of Cerebral Hemorrhage). Methods- Ischemic stroke patients with a previous intracerebral hemorrhage or multiple microbleeds were randomized to treatment with cilostazol or aspirin and followed up for a mean 1.8 years. Efficacy, defined as the composite of any stroke, myocardial infarction, and vascular death, and safety, defined as the incidence of hemorrhagic stroke, were analyzed in the 2 groups. Interactions between treatment and age, sex, presence of hypertension and diabetes mellitus, index of high-risk cerebral hemorrhage, and white matter lesion burden were analyzed for primary and key secondary outcomes. Changes in vital signs and laboratory results were compared in the 2 groups. Results- Among all 1534 patients enrolled, a significant interaction between treatment group and index of high risk for cerebral hemorrhage on hemorrhagic stroke (P for interaction, 0.03) was observed. Hemorrhagic stroke was less frequent in the cilostazol than in the aspirin group in patients with multiple microbleeds (1 versus 13 events; hazard ratio, 0.08 [95% CI, 0.01-0.61]; P=0.01). A marginal interaction between treatment group and white matter change on any stroke (P for interaction, 0.08) was observed. Cilostazol reduced any stroke significantly in patients with mild (5 versus 16 events; hazard ratio, 0.36 [95% CI, 0.13-0.97]; P=0.04)-to-moderate (16 versus 32 events; hazard ratio, 0.50 [95% CI, 0.29-0.92]; P=0.03) white matter changes. Heart rate and HDL (high-density lipoprotein) cholesterol level were significantly higher in the cilostazol group than in the aspirin group at follow-up. Conclusions- Cilostazol may be more beneficial for ischemic stroke patients with multiple cerebral microbleeds and before white matter changes are extensive. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01013532.
-
2.
Fatigue and activity after stroke. Secondary results from the Life After Stroke study.
Braaten, RS, Askim, T, Gunnes, M, Indredavik, B
Physiotherapy research international : the journal for researchers and clinicians in physical therapy. 2020;(4):e1851
Abstract
OBJECTIVES The aim of this study was to describe how the prevalence of fatigue changed from the subacute phase to the chronic phase after stroke, and to investigate how activity was associated with fatigue among participants included in the randomized controlled multicentre-study Life After STroke (LAST). METHODS The present study represents secondary analysis based on data from the LAST study. One-hundred-and-forty-five patients with mild and moderate stroke (mean (SD) age: 71.5 (10.5) years, 57.2% males) recruited from St. Olav's University Hospital were included. Fatigue was assessed by the Fatigue Severity Scale (FSS-7) at inclusion, 3 months after stroke, and at follow-up 18 months later. activPAL was used to measure activity at follow-up. RESULTS A total of 46 (31.7%) participants reported fatigue at inclusion and 43 (29.7%) at follow-up (p = .736). In the univariable regression analysis, sedentary behaviour, walking and sedentary bouts were significantly associated with fatigue (p ≤ .015), whereas only time spent walking was significantly associated with fatigue in the multivariable regression analysis (p = .017). CONCLUSIONS The present study showed that fatigue is a common symptom after stroke and that the prevalence of fatigue remained unchanged from the subacute to the chronic phase. The study also showed that increased time spent walking was strongly related to lower fatigue, while no such associations were found between the other activity categories and fatigue.
-
3.
The effect of dulaglutide on stroke: an exploratory analysis of the REWIND trial.
Gerstein, HC, Hart, R, Colhoun, HM, Diaz, R, Lakshmanan, M, Botros, FT, Probstfield, J, Riddle, MC, Rydén, L, Atisso, CM, et al
The lancet. Diabetes & endocrinology. 2020;(2):106-114
Abstract
BACKGROUND Cardiovascular outcome trials have suggested that glucagon-like peptide 1 (GLP-1) receptor agonists might reduce strokes. We analysed the effect of dulaglutide on stroke within the researching cardiovascular events with a weekly incretin in diabetes (REWIND) trial. METHODS REWIND was a multicentre, randomised, double-blind, placebo-controlled trial done at 371 sites in 24 countries. Men and women (aged ≥50 years) with established or newly detected type 2 diabetes whose HbA1c was 9·5% or less (with no lower limit) on stable doses of up to two oral glucose-lowering drugs with or without basal insulin therapy were eligible if their body-mass index was at least 23 kg/m2. Participants were randomly assigned (1:1) to weekly subcutaneous injections of either masked dulaglutide 1·5 mg or the same volume of masked placebo (containing the same excipients but without dulaglutide). Randomisation was done by a computer-generated random code with an interactive web response system with stratification by site. Participants, investigators, the trial leadership, and all other personnel were masked to treatment allocation until the trial was completed and the database was locked. During the treatment period, participants in both groups were instructed to inject study drug on the same day at around the same time, each week. Strokes were categorised as fatal or non-fatal, and as either ischaemic, haemorrhagic, or undetermined. Stroke severity was assessed using the modified Rankin scale. Participants were seen at 2 weeks, 3 months, 6 months, and then every 3 months for drug dispensing and every 6 months for detailed assessments, until 1200 confirmed primary outcomes accrued. The primary endpoint was the first occurrence of any component of the composite outcome, which comprised non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular or unknown causes. All analyses were done according to an intention-to-treat strategy that included all randomly assigned participants, irrespective of adherence. The trial is registered with ClinicalTrials.gov, number NCT01394952. FINDINGS Between Aug 18, 2011, and Aug 14, 2013, we screened 12 133 patients, of whom 9901 with type 2 diabetes and additional cardiovascular risk factors were randomly assigned to either dulaglutide (n=4949) or an equal volume of placebo (n=4952). During a median follow-up of 5·4 years, cerebrovascular and other cardiovascular outcomes were ascertained and adjudicated. 158 (3·2%) of 4949 participants assigned to dulaglutide and 205 (4·1%) of 4952 participants assigned to placebo had a stroke during follow-up (hazard ratio [HR] 0·76, 95% CI 0·62-0·94; p=0·010). Dulaglutide reduced ischaemic stroke (0·75, 0·59-0·94, p=0·012) but had no effect on haemorrhagic stroke (1·05, 0·55-1·99; p=0·89). Dulaglutide also reduced the composite of non-fatal stroke or all-cause death (0·88, 0·79-0·98; p=0·017) and disabling stroke (0·74, 0·56-0·99; p=0·042). The degree of disability after stroke did not differ by treatment group. INTERPRETATION Long-term dulaglutide use might reduce clinically relevant ischaemic stroke in people with type 2 diabetes but does not affect stroke severity. FUNDING Eli Lilly and Company.
-
4.
The predictive dysphagia score (PreDyScore) in the short- and medium-term post-stroke: a putative tool in PEG indication.
Gandolfo, C, Sukkar, S, , , Ceravolo, MG, Cortinovis, F, Finocchi, C, Gradaschi, R, Orlandoni, P, Reale, N, Ricci, S, et al
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2019;(8):1619-1626
Abstract
PURPOSE We performed an evaluation of dysphagia in an unselected series of strokes to identify factors causing persisting dysphagia at 1 month after onset and to formulate a predictive score. METHODS We evaluated the association between dysphagia and clinical aspects (univariate analysis) at the 7th and 30th days after admission. We performed a multivariate logistic regression at the 30th day on the factors that were significant. We computed a simple score for predicting persistent dysphagia. RESULTS We recruited 249 patients. At the 7th day, 94 patients were dysphagic (37.75%). Factors associated with dysphagia included TACI (OR 3.85), mRS ≥ 3 (OR 4.45), malnutrition (OR 2.69), and BMI ≥ 20 (OR 0.52). At the 30th day, 217 patients remained in the study, and dysphagia persisted in 75 (36.76%). The factors that were associated with dysphagia were age > 74 years (OR 1.99), TACI (OR 5.82), mRS score ≥ 3 (OR 4.31), malnutrition (OR 3.27), and BMI ≥ 20 (OR 0.45). The multivariate analysis indicated that mRS ≥ 3 (OR 1.80) and BMI ≥ 20 (OR 0.45) remained significantly associated with dysphagia. The best correlation with dysphagia was the sum of mRS and the reciprocal of the BMI multiplied by 100 ((mRS + 1 ∕ BMI) × 100). We named this score PreDyScore that ranged between 3.7 and 10.47. Using < 6 and > 8 as cutoffs, the sensitivity was 67.03%, and the specificity 95.65%. CONCLUSION BMI < 20 and mRS ≥ 3 are easily measurable bedside predictive factors of persistent dysphagia. PreDyScore showed good sensitivity and very good specificity and enables the prediction of persistent dysphagia with great accuracy in any clinical setting.
-
5.
Efficacy and mechanism of acupuncture for ischemic poststroke depression: Study protocol for a multicenter single-blinded randomized sham-controlled trial.
Lu, H, Li, M, Zhang, B, Ren, X, Meng, L, Bai, W, Wang, L, Wang, Z, Ding, S, Gan, Y, et al
Medicine. 2019;(7):e14479
-
-
Free full text
-
Abstract
INTRODUCTION Poststroke depression is a serious and common complication of stroke, especially the ischemic poststroke depression. Antidepressants are used in poststroke depression, and acupuncture may be an alternative approach. However, the efficacy and mechanism of acupuncture for poststroke depression has not been confirmed. METHODS/DESIGN This is a multicenter, central-randomized, single-blind, sham-controlled clinical trial. We will allocate 208 subjects aged between 40 and 80 years old, diagnosed with initial poststroke depression (PSD) within 6 months to 2 groups randomly in a ratio of 1:1. Patients in the experimental group will be treated with traditional acupuncture and placebo pills, whereas the others in the control group will be treated with sham-acupoints acupuncture and antidepressant (fluoxetine hydrochloride tablets). All will be given acupuncture and/or medication treatment for 12 weeks, and then received 12-week follow-up. Patients will be evaluated with the 17-item Hamilton Depression Scale and Se1f-rating Depression Scale for depression state, National Institute of Health Stroke Scale for neurological deficit, Modified Barthel Index for activities of daily living, Treatment Emergent Symptom Scale for side effects of treatments, diagnosis and evaluation criteria of traditional Chinese medicine for stroke (try out) for curative effects of stroke, and clinical global impression for synthesize effect before and the 2nd, 4th, 8th, and 12th week of treatment, 24th week of follow-up. Study on mechanisms of acupuncture will be revealed through the diversity of brain metabolites (choline-containing compounds [Cho], N-acetylaspartate [NAA], myoinositol, glutamine and glutamate complex, creatine [Cr], Cho/Cr, Cho/NAA, Cr/NAA) in bilateral dorsolateral prefrontal cortex and anterior cingulate cortex monitored by proton magnetic resonance spectroscopy, and serum monoamine neurotransmitters (5-hydroxytryptamine, norepinephrine, dopamine) and cytokines (brain-derived neurotrophic factor [BDNF], interleukin [IL]-4, IL-6, IL-10, IL-18, IL-1β, tumor necrosis factor alpha) before and the 12th week of treatment. Baseline characteristics of patients will be summarized by groups and compared with chi-square for categorical variables, and 2-sample t tests or Wilcoxon rank-sum test for the continuous variables. Primary and secondary outcomes according to the measurement times are applicable to univariate repetitive measurement deviation analysis or 2-sample t tests, or Wilcoxon rank-sum test. CONCLUSION The present research is designed to investigate efficacy and mechanism of traditional acupuncture therapy on ischemic PSD, also to explore the correlation between cerebra metabolic and serologic factors, and ischemic PSD. With this research, we are looking forward to find out an appropriate alternative nondrug therapy for PSD people to alleviate the adverse effects and drug dependence caused by antidepressants.
-
6.
Rationale and design to assess the efficacy and safety of HT047 in patients with acute ischemic stroke: A multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase II trial.
Heo, SH, Song, J, Kim, BJ, Kim, H, Chang, DI, ,
Medicine. 2019;(43):e17655
-
-
Free full text
-
Abstract
BACKGROUND Though several neuroprotective agents have been evaluated as potential treatments for acute ischemic stroke, none have demonstrated a definitive treatment efficacy, which remains elusive. HT047 is an herbal extract of Scutellaria baicalensis and Pueraria lobata, both of which have been widely used to treat ischemic stroke in traditional Korean medicine. The aims of this trial are to investigate whether HT047 can improve neurologic status, particularly motor function, in acute ischemic stroke patients, and to determine the safety of HT047. METHODS A multicenter, double-blind, randomized, placebo-controlled, 3-arm parallel group, phase II trial will be conducted in patients who have had an acute ischemic stroke within the past 14 days. The participating patients must have a Fugl-Meyer assessment (FMA) motor score ≤55, with arm or leg weakness, and Korean version of the National Institutes of Health Stroke scale (K-NIHSS) score of ≥4 and ≤15. Seventy-eight participants will be randomized in a 1:1:1 ratio and given high-dose HT047 (750 mg 3 times a day), low-dose HT047 (500 mg 3 times a day), or a placebo for 12 weeks. The primary endpoint is the change in FMA motor score between baseline and week 12. Secondary endpoints are as follows: the change in FMA motor score at weeks 4 and 8 from baseline; the change in FMA motor score at weeks 4, 8, and 12 from baseline according to the timing of treatment initiation (either within 1 week, or 1-2 weeks), or according to the presence of prognostic risk factors (hypertension, diabetes, dyslipidemia, etc); the change in K-NIHSS and Korean versions of the modified Rankin scale (K-mRS) and the modified Barthel index at weeks 4 and 12 from baseline; and the proportion of subjects at week 12 with a K-NIHSS score of 0 to 2, or with K-mRS scores of 0, ≤1, and ≤2. DISCUSSION This study is a 1st-in-human trial of HT047 to explore the efficacy and safety in acute ischemic stroke patients. The results will provide the appropriate dosage and evidence of therapeutic benefit of HT047 for stroke recovery. TRIAL REGISTRATION ClinicalTrials.gov (NCT02828540) Registered July 11, 2016.
-
7.
Optimizing early enteral nutrition in severe stroke (OPENS): protocol for a multicentre randomized controlled trial.
Yuan, F, Yang, F, Zhang, W, Jia, Y, Ma, Y, Qu, Y, Wang, X, Huo, K, Wang, C, Yuan, X, et al
BMC neurology. 2019;(1):24
Abstract
BACKGROUND Malnutrition is one of the crucial factors associated with poor prognosis in critical ill patients, yet a significant evidence gap surrounds the management of initial enteral feeding in severe stroke. The Optimizing Early Enteral Nutrition in Severe Stroke (OPENS) trial will compare a strategy of modified full enteral nutrition (EN) (standard full EN in conjunction with prokinetic drug) and a strategy of permissive underfeeding (40 to 60% of estimated caloric requirements) with standard full EN (advancement to target nutrition goals) in patients with severe stroke. METHODS The OPENS trial is a multicenter randomized controlled study. A total of 600 adult patients with severe stroke will be enrolled in 12 study sites in China, and randomized to standard full EN, modified full EN, or permissive underfeeding. The primary outcome measurement is the proportion of participants with a poor outcome (modified Rankin Scale ≥3) at day 90 of enrollment. Secondary outcomes include incidence rates of complications during hospitalization, disability at hospital discharge, and the ability of activities of daily living at day 90 of enrollment. The relationship between intervention and the primary outcome will be analyzed using multivariate logistic regression adjusted for study site, demographics, and baseline characteristics. DISCUSSION The OPENS trial will explore the optimum initial feeding strategy for acute severe stroke. This trial is, therefore, an important step in bridging the evidence gap surrounding the enteral feeding for patients with severe stroke during the first week of hospitalization. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02982668 ; First Posted: December 5, 2016.
-
8.
Traditional thromboprophylaxis in elderlies with atrial fibrillation: What we can achieve in real life.
Dubrava, M, Nemeth, F, Drobna, T, Gerlich, L
Bratislavske lekarske listy. 2019;(10):764-768
Abstract
OBJECTIVES To investigate real-world data on warfarinisation rates and results in the elderly patients with atrial fibrillation (AF). BACKGROUND AF is the most frequent arrhythmia in the elderlies with considerable risk of devastating stroke-related consequences. Guidelines prefer non-vitamin K antagonist oral anticoagulants (NOAC) to warfarin for thromboprophylaxis. Nevertheless, warfarin is still widely used, even if it is challenging, especially in polymorbid elderlies, to achieve the therapeutic international normalised ratio (INR). There are only scarce real-world data on INR in warfarinised elderly AF patients. METHODS The study was based on multicentric observational Slovak audit of atrial fibrillation in seniors (SAFIS) performed on 4,252 hospitalised AF patients aged over 64 years (mean age 80.9 yrs.). INR data from warfarinised patients were analysed (955 at admission and 870 at discharge). RESULTS At hospital admission and discharge, the warfarin medication rates were 22.6 % and 23.5 %, respectively, INR lower than 2 was present in 41.8 % and 30.6 % of patients, respectively, and INR higher than 3 was in 27.0 % and 7.7 %, respectively and altogether, 68.8 % and 38.3 % of warfarinised patients, respectively, were out of therapeutic range. CONCLUSION Warfarin is still frequently used in the elderlies with AF, but the success rates are unsatisfactory in a huge number of patients. It is urgent to improve seniors' access to NOAC (Fig. 2, Ref. 34).
-
9.
Combined electrical stimulation and exercise for swallow rehabilitation post-stroke: a pilot randomized control trial.
Sproson, L, Pownall, S, Enderby, P, Freeman, J
International journal of language & communication disorders. 2018;(2):405-417
Abstract
BACKGROUND Dysphagia is common after stroke, affecting up to 50% of patients initially. It can lead to post-stroke pneumonia, which causes 30% of stroke-related deaths, a longer hospital stay and poorer health outcomes. Dysphagia care post-stroke generally focuses on the management of symptoms, via modified oral intake textures and adapted posture, rather than direct physical rehabilitation of the swallowing function. Transcutaneous neuromuscular electrical stimulation (NMES) is a promising rehabilitation technology that can be used to stimulate swallowing; however, findings regarding efficacy have been conflicting. AIMS This pilot randomized controlled study involving three UK sites compared the efficacy of the Ampcare Effective Swallowing Protocol (ESP), combining NMES with swallow-strengthening exercises, with usual care in order to clarify evidence on NMES in the treatment of dysphagia post-stroke. A further objective was to pilot recruitment procedures and outcome measures in order to inform the design of a full-scale trial. METHODS & PROCEDURES Thirty patients were recruited and randomized into either (1) usual speech and language therapy dysphagia care; or (2) Ampcare ESP, receiving treatment 5 days/week for 4 weeks. Outcome measures included: the Functional Oral Intake Scale (FOIS), the Rosenbek Penetration-Aspiration Scale (PAS) and patient-reported outcomes (Swallow Related Quality of Life-SWAL-QOL). OUTCOMES & RESULTS Thirty patients were recruited; 15 were randomized to the Ampcare ESP intervention arm and 15 to usual care. A greater proportion (75%, or 9/12) of patients receiving Ampcare ESP improved compared with 57% (or 8/14) of the usual-care group. Patients receiving Ampcare ESP also made clinically meaningful change (a comparative benefit of 1.5 on the FOIS, and on the PAS: 1.35 for diet and 0.3 for fluids) compared with usual care. The intervention group also reported much better outcome satisfaction. CONCLUSIONS & IMPLICATIONS The pilot demonstrated successful recruitment, treatment safety and tolerability and clinically meaningful outcome improvements, justifying progression to a fully powered study. It also showed clinically meaningful treatment trends for the Ampcare ESP intervention.
-
10.
Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial.
Kasner, SE, Swaminathan, B, Lavados, P, Sharma, M, Muir, K, Veltkamp, R, Ameriso, SF, Endres, M, Lutsep, H, Messé, SR, et al
The Lancet. Neurology. 2018;(12):1053-1060
-
-
Free full text
-
Abstract
BACKGROUND Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial. METHODS NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy. FINDINGS Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were followed up for a mean of 11 months because of early trial termination. PFO was reported as present in 534 (7·4%) patients on the basis of either TTE or TOE. Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke rate of 4·8 events per 100 person-years compared with 2·6 events per 100 person-years in those treated with rivaroxaban. Among patients with known PFO, there was insufficient evidence to support a difference in risk of recurrent ischaemic stroke between rivaroxaban and aspirin (hazard ratio [HR] 0·54; 95% CI 0·22-1·36), and the risk was similar for those without known PFO (1·06; 0·84-1·33; pinteraction=0·18). The risks of major bleeding with rivaroxaban versus aspirin were similar in patients with PFO detected (HR 2·05; 95% CI 0·51-8·18) and in those without PFO detected (HR 2·82; 95% CI 1·69-4·70; pinteraction=0·68). The random-effects meta-analysis combined data from NAVIGATE ESUS with data from two previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0·48 (95% CI 0·24-0·96; p=0·04) for ischaemic stroke in favour of anticoagulation, without evidence of heterogeneity. INTERPRETATION Among patients with ESUS who have PFO, anticoagulation might reduce the risk of recurrent stroke by about half, although substantial imprecision remains. Dedicated trials of anticoagulation versus antiplatelet therapy or PFO closure, or both, are warranted. FUNDING Bayer and Janssen.