Tranexamic Acid for Prevention of Hematoma Expansion in Intracerebral Hemorrhage Patients With or Without Spot Sign.

BACKGROUND AND PURPOSE: The computed tomography angiography or contrast-enhanced computed tomography based spot sign has been proposed as a biomarker for identifying on-going hematoma expansion in patients with acute intracerebral hemorrhage. We investigated, if spot-sign positive participants benefit more from tranexamic acid versus placebo as compared to spot-sign negative participants. METHODS: TICH-2 trial (Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage) was a randomized, placebo-controlled clinical trial recruiting acutely hospitalized participants with intracerebral hemorrhage within 8 hours after symptom onset. Local investigators randomized participants to 2 grams of intravenous tranexamic acid or matching placebo (1:1). All participants underwent computed tomography scan on admission and on day 2 (24±12 hours) after randomization. In this sub group analysis, we included all participants from the main trial population with imaging allowing adjudication of spot sign status. RESULTS: Of the 2325 TICH-2 participants, 254 (10.9%) had imaging allowing for spot-sign adjudication. Of these participants, 64 (25.2%) were spot-sign positive. Median (interquartile range) time from symptom onset to administration of the intervention was 225.0 (169.0 to 310.0) minutes. The adjusted percent difference in absolute day-2 hematoma volume between participants allocated to tranexamic versus placebo was 3.7% (95% CI, -12.8% to 23.4%) for spot-sign positive and 1.7% (95% CI, -8.4% to 12.8%) for spot-sign negative participants (Pheterogenity=0.85). No difference was observed in significant hematoma progression (dichotomous composite outcome) between participants allocated to tranexamic versus placebo among spot-sign positive (odds ratio, 0.85 [95% CI, 0.29 to 2.46]) and negative (odds ratio, 0.77 [95% CI, 0.41 to 1.45]) participants (Pheterogenity=0.88). CONCLUSIONS: Data from the TICH-2 trial do not support that admission spot sign status modifies the treatment effect of tranexamic acid versus placebo in patients with acute intracerebral hemorrhage. The results might have been affected by low statistical power as well as treatment delay. Registration: URL: http://www.controlled-trials.com; Unique identifier: ISRCTN93732214.

European Stroke Organisation (ESO) guideline on pharmacological interventions for long-term secondary prevention after ischaemic stroke or transient ischaemic attack.

Recurrent stroke affects 9% to 15% of people within 1 year. This European Stroke Organisation (ESO) guideline provides evidence-based recommendations on pharmacological management of blood pressure (BP), diabetes mellitus, lipid levels and antiplatelet therapy for the prevention of recurrent stroke and other important outcomes in people with ischaemic stroke or transient ischaemic attack (TIA). It does not cover interventions for specific causes of stroke, including anticoagulation for cardioembolic stroke, which are addressed in other guidelines. This guideline was developed through ESO standard operating procedures and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. The working group identified clinical questions, selected outcomes, performed systematic reviews, with meta-analyses where appropriate, and made evidence-based recommendations, with expert consensus statements where evidence was insufficient to support a recommendation. To reduce the long-term risk of recurrent stroke or other important outcomes after ischaemic stroke or TIA, we recommend: BP lowering treatment to a target of <130/80 mmHg, except in subgroups at increased risk of harm; HMGCoA-reductase inhibitors (statins) and targeting a low density lipoprotein level of <1.8 mmol/l (70 mg/dl); avoidance of dual antiplatelet therapy with aspirin and clopidogrel after the first 90 days; to not give direct oral anticoagulant drugs (DOACs) for embolic stroke of undetermined source and to consider pioglitazone in people with diabetes or insulin resistance, after careful consideration of potential risks. In addition to the evidence-based recommendations, all or the majority of working group members supported: out-of-office BP monitoring; use of combination treatment for BP control; consideration of ezetimibe or PCSK9 inhibitors when lipid targets are not achieved; consideration of use of low-dose DOACs in addition to an antiplatelet in selected groups of people with coronary or peripheral artery disease and aiming for an HbA1c level of <53 mmol/mol (7%) in people with diabetes mellitus. These guidelines aim to standardise long-term pharmacological treatment to reduce the burden of recurrent stroke in Europe.

Relationship between left atrial strain, diastolic dysfunction and subclinical atrial fibrillation in patients with cryptogenic stroke: the SURPRISE echo substudy.

Paroxysmal atrial fibrillation (PAF) may be the cause of a substantial part of cryptogenic strokes (CS). Echocardiography could assist risk stratification for PAF to select patients in need of prolonged rhythm monitoring. We aimed to assess the value of left atrial (LA) strain and a revised diastolic dysfunction (DDF) model with LA strain for predicting PAF. This was a prospective study of 56 CS patients who had a cardiac monitor implanted for 3 year monitoring for PAF, and an echocardiogram performed prior to monitoring. Conventional echocardiography, global longitudinal strain (GLS) and LA strain were performed. LA speckle tracking provided the LA reservoir strain (LAs). Patients were stratified into high versus low LAs by ROC curves (28.2%), and this cut-off was used to refine DDF grading. During follow-up of median 20 months, 13 (23%) patients were diagnosed with PAF. No conventional echocardiographic parameters differed between patients who developed PAF and those without PAF. However, LAs was significantly impaired in PAF patients (LAs: 30 vs. 27% for non-PAF and PAF, p = 0.046). Low LAs significantly predicted PAF independent of LA volume and GLS [OR 5.88 (1.30; 26.55), p = 0.021]. Revised DDF grading significantly predicted PAF, even when adjusted for the CHADS2 risk-score (OR 1.88 [1.01;3.50], per increase in DDF grade, p for trend = 0.047), which was not the case for conventional DDF grading. In conclusion, LAs associates with PAF independent of GLS and LA size, and may be used to improve the performance of DDF grading for identifying PAF in CS patients.

Use of oral anticoagulation therapy in atrial fibrillation after stroke: results from a nationwide registry.

Background. The knowledge is still sparse about patient related factors, influencing oral anticoagulation therapy (OAC) rates, in stroke patients with atrial fibrillation (AF). Aims. To assess the use of OAC in ischemic stroke patients diagnosed with AF and to identify patient related factors influencing the initiation of OAC. Methods. In the nationwide Danish Stroke Registry we identified 55,551 patients admitted with acute ischemic stroke from 2003 to 2011. Frequency analysis was used to assess the use of OAC in patients with AF, and logistic regression was used to determine independent predictors of OAC. Results. 17.1% (n = 9,482) of ischemic stroke patients had AF. OAC prescription rates were increasing, and in 2011 46.6% were prescribed OAC, 42.5% had a contraindication, and 3.7% were not prescribed OAC without a stated contraindication. Younger age, less severe stroke, and male gender were positive predictors of OAC, while excessive alcohol consumption, smoking, and institutionalization were negative predictors of OAC (P values < 0.05). Conclusions. Advanced age, severe stroke, female gender, institutionalization, smoking, and excessive alcohol consumption were associated with lower OAC rates. Contraindications were generally present in patients not in therapy, and the assumed underuse of OAC may be overestimated.