One-Year Risk of Stroke after Transient Ischemic Attack or Minor Stroke

BACKGROUND Previous studies conducted between 1997 and 2003 estimated that the risk of stroke or an acute coronary syndrome was 12 to 20% during the first 3 months after a transient ischemic attack (TIA) or minor stroke. The TIAregistry.org project was designed to describe the contemporary profile, etiologic factors, and outcomes in patients with a TIA or minor ischemic stroke who receive care in health systems that now offer urgent evaluation by stroke specialists. METHODS We recruited patients who had had a TIA or minor stroke within the previous 7 days. Sites were selected if they had systems dedicated to urgent evaluation of patients with TIA. We estimated the 1-year risk of stroke and of the composite outcome of stroke, an acute coronary syndrome, or death from cardiovascular causes. We also examined the association of the ABCD2 score for the risk of stroke (range, 0 [lowest risk] to 7 [highest risk]), findings on brain imaging, and cause of TIA or minor stroke with the risk of recurrent stroke over a period of 1 year. RESULTS From 2009 through 2011, we enrolled 4789 patients at 61 sites in 21 countries. A total of 78.4% of the patients were evaluated by stroke specialists within 24 hours after symptom onset. A total of 33.4% of the patients had an acute brain infarction, 23.2% had at least one extracranial or intracranial stenosis of 50% or more, and 10.4% had atrial fibrillation. The Kaplan–Meier estimate of the 1-year event rate of the composite cardiovascular outcome was 6.2% (95% confidence interval, 5.5 to 7.0). Kaplan–Meier estimates of the stroke rate at days 2, 7, 30, 90, and 365 were 1.5%, 2.1%, 2.8%, 3.7%, and 5.1%, respectively. In multivariable analyses, multiple infarctions on brain imaging, large-artery atherosclerosis, and an ABCD2 score of 6 or 7 were each associated with more than a doubling of the risk of stroke. CONCLUSIONS We observed a lower risk of cardiovascular events after TIA than previously reported. The ABCD2 score, findings on brain imaging, and status with respect to large-artery atherosclerosis helped stratify the risk of recurrent stroke within 1 year after a TIA or minor stroke. (Funded by Sanofi and Bristol-Myers Squibb.)Supported by an unrestricted grant from Sanofi and Bristol-Myers Squibb

Individual participant data analysis of two trials on aldosterone blockade in myocardial infarction

Background: Two recent randomised trials studied the benefit of mineralocorticoid receptor antagonists (MRAs) in ST-segment elevation myocardial infarction (STEMI) irrespective or in absence of heart failure. The studies were both undersized to assess hard clinical endpoints. A pooled analysis was preplanned by the steering committees. Methods: We conducted a prespecified meta-analysis of patient-level data of patients with STEMI recruited in two multicentre superiority trials, randomised within 72 hours after symptom onset. Patients were allocated (1:1) to two MRA regimens: (1) an intravenous bolus of potassium canrenoate (200 mg) followed by oral spironolactone (25 mg once daily) versus standard therapy or (2) oral eplerenone (25–50 mg) versus placebo. The primary and key secondary outcomes, all-cause death and the composite of all-cause death or resuscitated sudden death, respectively, were assessed in the intention-to-treat population using a Cox model stratified on the study identifier. Results: Patients were randomly assigned to receive (n=1118) or not the MRA regimen (n=1123). After a median follow-up time of 188 days, the primary and secondary outcomes occurred in 5 (0.4%) and 17 (1.5%) patients (adjusted HR (adjHR) 0.31, 95% CI 0.11 to 0.86, p=0.03) and 6 (0.5%) and 22 (2%) patients (adjHR 0.26, 95% CI 0.10 to 0.65, p=0.004) in the MRA and control groups, respectively. There were also trends towards lower rates of cardiovascular death (p=0.06) and ventricular fibrillation (p=0.08) in the MRA group. Conclusion: Our analysis suggests that compared with standard therapy, MRA regimens are associated with a reduction of death and death or resuscitated sudden death in STEMI

Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial

Background The clinical benefit of preventive eradication of unruptured brain arteriovenous malformations remains uncertain. A Randomised trial of Unruptured Brain Arteriovenous malformations (ARUBA) aims to compare the risk of death and symptomatic stroke in patients with an unruptured brain arteriovenous malformation who are allocated to either medical management alone or medical management with interventional therapy. Methods Adult patients (\u3e= 18 years) with an unruptured brain arteriovenous malformation were enrolled into this trial at 39 clinical sites in nine countries. Patients were randomised (by web-based system, in a 1: 1 ratio, with random permuted block design [block size 2, 4, or 6], stratified by clinical site) to medical management with interventional therapy (ie, neurosurgery, embolisation, or stereotactic radiotherapy, alone or in combination) or medical management alone (ie, pharmacological therapy for neurological symptoms as needed). Patients, clinicians, and investigators are aware of treatment assignment. The primary outcome is time to the composite endpoint of death or symptomatic stroke; the primary analysis is by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00389181. Findings Randomisation was started on April 4, 2007, and was stopped on April 15, 2013, when a data and safety monitoring board appointed by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health recommended halting randomisation because of superiority of the medical management group (log-rank Z statistic of 4.10, exceeding the prespecified stopping boundary value of 2.87). At this point, outcome data were available for 223 patients (mean follow-up 33.3 months [SD 19.7]), 114 assigned to interventional therapy and 109 to medical management. The primary endpoint had been reached by 11 (10.1%) patients in the medical management group compared with 35 (30.7%) in the interventional therapy group. The risk of death or stroke was significantly lower in the medical management group than in the interventional therapy group (hazard ratio 0.27, 95% CI 0.14-0.54). No harms were identified, other than a higher number of strokes (45 vs 12,

Assessment of smoking care by stroke specialists in patients with recent TIA and minor stroke: an international prospective registry-based cohort study

Objectives: The objectives are to assess smoking abstinence and its effects on vascular risk and to report tobacco-cessation counselling and pharmacotherapy use in patients who had a recent minor stroke or transient ischaemic attack (TIA). Design and setting: The TIA registry.org project is a prospective, observational registry of patients with TIA and minor stroke that occurred in the previous 7 days with a 5-year follow-up, involving 61 sites with stroke specialists in 21 countries (Europe, Asia, Latin America and Middle East). Of those, 42 sites had 5-year follow-up data on more than 50% of their patients and were included in the present study. Participants: From June 2009 through December 2011, 3847 patients were eligible for the study (80% of the initial cohort). Outcomes: Tobacco counselling and smoking-cessation pharmacotherapy use in smoking patients were reported at discharge. Association between 3-month smoking status and risk of a major cardiovascular event (MACE) was analysed with multivariable Cox regression model. Results: Among 3801 patients included, 835 (22%) were smokers. At discharge, only 35.2% have been advised to quit and 12.5% had smoking-cessation pharmacotherapy prescription. At 3 months, 383/835 (46.9%) baseline smokers were continuers. Living alone and alcohol abuse were associated with persistent smoking; high level of education, aphasia and dyslipidaemia with quitting. The adjusted HRs for MACE at 5 years were 1.13 (95% CI 0.90 to 1.43) in former smokers, 1.31 (95% CI 0.93 to 1.84) in quitters and 1.31 (95% CI 0.94 to 1.83) in continuers. Using time-varying analysis, current smoking at the time of MACE non-significantly increased the risk of MACE (HR 1.31 (95% CI 0.97 to 1.78); p=0.080). Conclusion: In the TIAregistry.org, smoking-cessation intervention was used in a minority of patients. Surprisingly, in this population in which, at 5 years, other vascular risk factors were well controlled and antithrombotic treatment maintained, smoking cessation non-significantly decreased the risk of MACE

Pre-hospital administration of ticagrelor in diabetic patients with ST-elevation myocardial infarction undergoing primary angioplasty: A sub-analysis of the ATLANTIC trial

Objective: We investigated, in the contemporary era of ST-elevation myocardial infarction (STEMI) treatment, the influence of diabetes mellitus (DM) on cardiovascular outcomes, and whether pre-hospital administration of ticagrelor may affect these outcomes in a subgroup of STEMI patients with DM. Background: DM patients have high platelet reactivity and a prothrombotic condition which highlight the importance of an effective antithrombotic regimen in this high-risk population. Methods: In toal 1,630 STEMI patients enrolled in the ATLANTIC trial who underwent primary percutaneous coronary intervention (PCI) were included. Multivariate analysis was used to explore the association of DM with outcomes and potential treatment-by-diabetes interaction was tested. Results: A total of 214/1,630 (13.1%) patients had DM. DM was an independent predictor of poor myocardial reperfusion as reflected by less frequent ST-segment elevation resolution ( 6570%) after PCI (OR 0.59, 95% CI 0.43\u20130.82, P < 0.01) and was an independent predictor of the composite 30-day outcomes of death/new myocardial infarction (MI)/urgent revascularization/definite stent thrombosis (ST) (OR 2.80, 95% CI 1.62\u20134.85, P < 0.01), new MI or definite acute ST (OR 2.46, 95% CI 1.08\u20135.61, P = 0.03), and definite ST (OR 10.00, 95% CI 3.54\u201328.22, P < 0.01). No significant interaction between pre-hospital ticagrelor vs in-hospital ticagrelor administration and DM was present for the clinical, electrocardiographic and angiographic outcomes as well as for thrombolysis in myocardial infarction major bleeding. Conclusions: DM remains independently associated with poor myocardial reperfusion and worse 30-day clinical outcomes. No significant interaction was found between pre-hospital vs in-hospital ticagrelor administration and DM status. Further approaches for the treatment of DM patients are needed. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01347580

Impact of presentation and transfer delays on complete ST-segment resolution before primary percutaneous coronary intervention: Insights from the ATLANTIC trial

Aims: The aim of this study was to identify predictors of complete ST-segment resolution (STR) pre-primary percutaneous coronary intervention (PCI) in patients enrolled in the ATLANTIC trial. Methods and results: ECGs recorded at the time of inclusion (pre-hospital [pre-H]-ECG) and in the catheterisation laboratory before angiography (pre-PCI-ECG) were analysed by an independent core laboratory. Complete STR was defined as 6570%. Complete STR occurred pre-PCI in 12.8% (204/1, 598) of patients and predicted lower 30-day composite MACCE (OR=0.10, 95% CI: 0.002-0.57, p=0.001) and total mortality (OR=0.16, 95% CI: 0.004-0.95, p=0.035). Independent predictors of complete STR included the time from index event to pre-H-ECG (OR=0.94, 95% CI: 0.89-1.00, p=0.035), use of heparins before pre- PCI-ECG (OR=1.75, 95% CI: 1.25-2.45, p=0.001) and time from pre-H-ECG to pre-PCI-ECG (OR=1.09, 95% CI: 1.03-1.16, p=0.005). In the pre-H ticagrelor group, patients with complete STR had a significantly longer delay between pre-H-ECG and pre-PCI-ECG compared to patients without complete STR (median 53 [44-73] vs. 49 [38.5-61] mins, p=0.001); however, this was not observed in the control group (in-hospital ticagrelor) (50 [40-67] vs. 49 [39-61] mins, p=0.258). Conclusions: Short patient delay, early administration of anticoagulant and ticagrelor if a long transfer delay is expected may help to achieve reperfusion prior to PCI. Pre-H treatment may be beneficial in patients with longer transfer delays, allowing the drug to become biologically active. ClinicalTrials.gov Identifier: NCT01347580

Glucocorticoids for acute urticaria: study protocol for a double-blind non-inferiority randomised controlled trial

INTRODUCTION: This study protocol describes a trial designed to investigate whether antihistamine alone in patients with acute urticaria does not increase the 7-day Urticaria Activity Score (UAS7) in comparison with an association of antihistamine and glucocorticoids and reduces short-term relapses and chronic-induced urticaria. METHODS AND ANALYSIS: This is a prospective, double-blind, parallel-group, multicentre non-inferiority randomised controlled trial. Two-hundred and forty patients with acute urticaria admitted to emergency department will be randomised in a 1:1 ratio to receive levocetirizine or an association of levocetirizine and prednisone. Randomisation will be stratified by centre. The primary outcome will be the UAS7 at day 7. The secondary outcomes will encompass recurrence of hives and/or itch at day 7; occurrence of spontaneous hives or itch for &gt;6 weeks; patients with angioedema at day 7, and 2, 6, 12 and 24 weeks; new emergency visits for acute urticaria recurrences at days 7 and 14, and 3 months; Dermatology Life Quality Index at days 7 and 14, and 3 and 6 months; and Chronic Urticaria Quality of Life Questionnaire at 6 weeks. ETHICS AND DISSEMINATION: The protocol has been approved by the and will be carried out in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. A steering committee will oversee the progress of the study. Findings will be disseminated through national and international scientific conferences and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03545464

Reduced-Dose Intravenous Thrombolysis for Acute Intermediate-High-risk Pulmonary Embolism: Rationale and Design of the Pulmonary Embolism International THrOmbolysis (PEITHO)-3 trial

Intermediate-high-risk pulmonary embolism (PE) is characterized by right ventricular (RV) dysfunction and elevated circulating cardiac troponin levels despite apparent hemodynamic stability at presentation. In these patients, full-dose systemic thrombolysis reduced the risk of hemodynamic decompensation or death but increased the risk of life-threatening bleeding. Reduced-dose thrombolysis may be capable of improving safety while maintaining reperfusion efficacy. The Pulmonary Embolism International THrOmbolysis (PEITHO)-3 study (ClinicalTrials.gov Identifier: NCT04430569) is a randomized, placebo-controlled, double-blind, multicenter, multinational trial with long-term follow-up. We will compare the efficacy and safety of a reduced-dose alteplase regimen with standard heparin anticoagulation. Patients with intermediate-high-risk PE will also fulfill at least one clinical criterion of severity: systolic blood pressure ≤110 mm Hg, respiratory rate &gt;20 breaths/min, or history of heart failure. The primary efficacy outcome is the composite of all-cause death, hemodynamic decompensation, or PE recurrence within 30 days of randomization. Key secondary outcomes, to be included in hierarchical analysis, are fatal or GUSTO severe or life-threatening bleeding; net clinical benefit (primary efficacy outcome plus severe or life-threatening bleeding); and all-cause death, all within 30 days. All outcomes will be adjudicated by an independent committee. Further outcomes include PE-related death, hemodynamic decompensation, or stroke within 30 days; dyspnea, functional limitation, or RV dysfunction at 6 months and 2 years; and utilization of health care resources within 30 days and 2 years. The study is planned to enroll 650 patients. The results are expected to have a major impact on risk-adjusted treatment of acute PE and inform guideline recommendations

Efficacy and Safety of Glycoprotein IIb/IIIa Inhibitors on Top of Ticagrelor in STEMI: A Subanalysis of the ATLANTIC Trial

BACKGROUND: Glycoprotein IIb/IIIa inhibitors (GPIs) in combination with clopidogrel improve clinical outcome in ST-elevation myocardial infarction (STEMI); however, finding a balance that minimizes both thrombotic and bleeding risk remains fundamental. The efficacy and safety of GPI in addition to ticagrelor, a more potent P2Y12-inhibitor, have not been fully investigated. METHODS: 1,630 STEMI patients who underwent primary percutaneous coronary intervention (PCI) were analyzed in this subanalysis of the ATLANTIC trial. Patients were divided in three groups: no GPI, GPI administration routinely before primary PCI, and GPI administration in bailout situations. The primary efficacy outcome was a composite of death, myocardial infarction, urgent target revascularization, and definite stent thrombosis at 30 days. The safety outcome was non-coronary artery bypass graft (CABG)-related PLATO major bleeding at 30 days. RESULTS: Compared with no GPI (n\u2009=\u2009930), routine GPI (n\u2009=\u2009525) or bailout GPI (n\u2009=\u2009175) was not associated with an improved primary efficacy outcome (4.2% no GPI vs. 4.0% routine GPI vs. 6.9% bailout GPI; p\u2009=\u20090.58). After multivariate analysis, the use of GPI in bailout situations was associated with a higher incidence of non-CABG-related bleeding compared with no GPI (odds ratio [OR] 2.96, 95% confidence interval [CI] 1.32-6.64; p\u2009=\u20090.03). However, routine GPI use compared with no GPI was not associated with a significant increase in bleeding (OR 1.78, 95% CI 0.88-3.61; p\u2009=\u20090.92). CONCLUSION: Use of GPIs in addition to ticagrelor in STEMI patients was not associated with an improvement in 30-day ischemic outcome. A significant increase in 30-day non-CABG-related PLATO major bleeding was seen in patients who received GPIs in a bailout situation

Prevalence of fibromyalgia in France: a multi-step study research combining national screening and clinical confirmation: The DEFI study (Determination of Epidemiology of FIbromyalgia)

<p>Abstract</p> <p>Background</p> <p>Fibromyalgia is a common disease, but little is known on its real prevalence in France. This epidemiological study aimed to assess fibromyalgia (FM) prevalence in the French metropolitan population, based on a multi-step sampling analysis, combining national screening and clinical confirmation by trained specialists.</p> <p>Methods</p> <p>a sampling method on the entire national territory was used: patients over 18 years of age accepting to take part in the study were contacted by telephone using the LFES Questionnaire, a screening test for FM. The, for patients detected by the LFESQ, a visit with a FM-trained rheumatologist was proposed to confirm FM, based on 1990 ACR criteria. Each detected patient completed the following self-questionnaires: SF36, HADS, stress VAS, Co-morbidities and Regional pain score.</p> <p>Results</p> <p>3081 patients were contacted in 5 representative French regions, of which 232 patients were screened for FM. A fibromyalgia diagnosis was then confirmed by rheumatologist in 20 cases (17 female and 3 male, 56.9 ± 13.2 years). The final estimated FM prevalence was 1.6 (CI95: 1.2%; 2.0%). No significant difference was detected between the patients accepting (CS+) and refusing (CS-) rheumatologist visit for the SF36 score, regional pain score, stress VAS scale and co-morbidities. In patients detected for FM by the LFESQ, we found a statistically significant decrease in quality of life and a statistically significant increase in stress level in patients with a confirmed diagnosis (FM+) (6.3 ± 1.9) compared to patients with an invalidated diagnosis (FM-) (4.4 ± 2.8; p = 0.007). The study also demonstrated a significant association, independently of ACR criteria, between the diagnosis of FM and several factors such as regional pain score > 10, elevated stress level, low SF36 scale score and presence of gastro-intestinal disorder co-morbidities.</p> <p>Conclusion</p> <p>Fibromyalgia is a common condition; the 1.6% prevalence calculated in the French population in our study corroborates the figures published in the European literature. Our results also suggest that criteria such as regional pain score, stress level or SF36 quality of life, could represent useful tools in fibromyalgia diagnosis.</p