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Potential missed opportunities to prevent ischaemic stroke: prospective multicentre cohort study of atrial fibrillation-associated ischaemic stroke and TIA.

ABSTRACT: OBJECTIVE:We report on: (1) the proportion of patients with known atrial fibrillation (AF); and (2) demographic, clinical or radiological differences between patients with known AF (and not treated) and patients with newly diagnosed AF, in a cohort of patients who presented with ischaemic stroke or transient ischaemic attack (TIA) not previously treated with anticoagulation. DESIGN:We reviewed cross-sectional baseline demographic and clinical data from a prospective observational cohort study, (CROMIS-2). SETTING:Patients were recruited from 79 hospital stroke centres throughout the UK and one centre in the Netherlands. PARTICIPANTS:Patients were eligible if they were adults who presented with ischaemic stroke or TIA and AF and had not been previously treated with oral anticoagulation. MAIN OUTCOME MEASURES:Proportion of patients with known AF before index ischaemic stroke or TIA from a cohort of patients who have not been previously treated with oral anticoagulation. Secondary analysis includes the comparison of CHA2DS2-VASc and HAS-BLED scores and other demographics and risk factors between those with newly diagnosed AF and those with previously known AF. RESULTS:Of 1470 patients included in the analysis (mean age 76 years (SD 10)), 622 (42%) were female; 999 (68%) patients had newly diagnosed AF and 471 (32%) patients had known AF. Of the 471 patients with known AF, 68% had a strong indication for anticoagulation and 89% should have been considered for anticoagulation based upon CHA2DS2-VASc score. Patients with known AF were more likely to have a prior history of dementia (4% vs 2%, p=0.02) and had higher HAS-BLED scores (median 3 vs 2). CHA2DS2-VASc, other risk factors and demographics were similar. CONCLUSIONS:About 1/3 of patients who present with stroke and have AF who have not been treated with oral anticoagulation have previously known AF. Of these patients, at least 68% were not adequately treated with oral anticoagulation. TRIAL REGISTRATION NUMBER:NCT02513316.

SUBMITTER: Wilson D

PROVIDER: S-EPMC6661679 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Potential missed opportunities to prevent ischaemic stroke: prospective multicentre cohort study of atrial fibrillation-associated ischaemic stroke and TIA.

Wilson Duncan D Ambler Gareth G Shakeshaft Clare C Banerjee Gargi G Charidimou Andreas A Seiffge David D White Mark M Cohen Hannah H Yousry Tarek T Salman R Al-Shahi AS Lip Gregory Y H GYH Muir Keith K Brown Martin M MM Jäger H R HR Werring David J DJ

BMJ open 20190724 7

<h4>Objective</h4>We report on: (1) the proportion of patients with known atrial fibrillation (AF); and (2) demographic, clinical or radiological differences between patients with known AF (and not treated) and patients with newly diagnosed AF, in a cohort of patients who presented with ischaemic stroke or transient ischaemic attack (TIA) not previously treated with anticoagulation.<h4>Design</h4>We reviewed cross-sectional baseline demographic and clinical data from a prospective observational ...[more]

PMID: 31345970

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Project description:ObjectiveTo validate the previously derived Canadian TIA Score to stratify subsequent stroke risk in a new cohort of emergency department patients with transient ischaemic attack.DesignProspective cohort study.Setting13 Canadian emergency departments over five years.Participants7607 consecutively enrolled adult patients attending the emergency department with transient ischaemic attack or minor stroke.Main outcome measuresThe primary outcome was subsequent stroke or carotid endarterectomy/carotid artery stenting within seven days. The secondary outcome was subsequent stroke within seven days (with or without carotid endarterectomy/carotid artery stenting). Telephone follow-up used the validated Questionnaire for Verifying Stroke Free Status at seven and 90 days. All outcomes were adjudicated by panels of three stroke experts, blinded to the index emergency department visit.ResultsOf the 7607 patients, 108 (1.4%) had a subsequent stroke within seven days, 83 (1.1%) had carotid endarterectomy/carotid artery stenting within seven days, and nine had both. The Canadian TIA Score stratified the risk of stroke, carotid endarterectomy/carotid artery stenting, or both within seven days as low (risk ≤0.5%; interval likelihood ratio 0.20, 95% confidence interval 0.09 to 0.44), medium (risk 2.3%; interval likelihood ratio 0.94, 0.85 to 1.04), and high (risk 5.9% interval likelihood ratio 2.56, 2.02 to 3.25) more accurately (area under the curve 0.70, 95% confidence interval 0.66 to 0.73) than did the ABCD2 (0.60, 0.55 to 0.64) or ABCD2i (0.64, 0.59 to 0.68). Results were similar for subsequent stroke regardless of carotid endarterectomy/carotid artery stenting within seven days.ConclusionThe Canadian TIA Score stratifies patients' seven day risk for stroke, with or without carotid endarterectomy/carotid artery stenting, and is now ready for clinical use. Incorporating this validated risk estimate into management plans should improve early decision making at the index emergency visit regarding benefits of hospital admission, timing of investigations, and prioritisation of specialist referral.

Project description:IntroductionStroke is a major health problem and transient ischaemic attack (TIA) is an important risk factor for stroke. Primary prevention of stroke and TIA will have the greatest impact on reducing the burden of these conditions. Evidence-based guidelines for stroke/TIA prevention identify individuals eligible for preventative interventions in primary care. This study will investigate: (1) the proportion of strokes/TIAs with prior missed opportunities for prevention in primary care; (2) the influence of patient characteristics on missed prevention opportunities and (3) how the proportion of missed prevention opportunities has changed over time.Methods and analysisA retrospective case review will identify first-ever stroke and patients with TIA between 2000 and 2013 using anonymised electronic medical records extracted from the health improvement network (THIN) database. Four categories of missed opportunities for stroke/TIA prevention will be sought: untreated high blood pressure in patients eligible for treatment (either blood pressure ≥160/100 or ≥140/90 mm Hg in patients at high cardiovascular disease (CVD) risk); patients with atrial fibrillation with high stroke risk and no anticoagulant therapy; no lipid modifying drug therapy prescribed in patients at high CVD risk or with familial hypercholesterolaemia. The proportion of patients with each missed opportunity and multiple missed opportunities will be calculated. Mixed effect logistic regression will model the relationship between demographic and patient characteristics and missed opportunities for care; practice will be included as a random effect.Ethics and disseminationTHIN data collection was approved by the NHS South East Multi-centre Research Ethics Committee (MREC) in 2003. This study was approved by the independent scientific review committee in May 2013. Dissemination of findings has the potential to change practice, improve the quality of care provided to patients and ultimately reduce the incidence of strokes and TIAs. Findings will be published in a peer-reviewed journal and disseminated at national and international conferences.

Project description:BackgroundAbout 13-26% of all acute ischaemic strokes are related to non-valvular atrial fibrillation, the most common cardiac arrhythmia globally. Deciding when to initiate oral anticoagulation in patients with non-valvular atrial fibrillation is a longstanding, common, and unresolved clinical challenge. Although the risk of early recurrent ischaemic stroke is high in this population, early oral anticoagulation is suspected to increase the risk of potentially harmful intracranial haemorrhage, including haemorrhagic transformation of the infarct. This assumption, and current treatment guidelines, are based on historical, mostly observational data from patients with ischaemic stroke and atrial fibrillation treated with heparins, heparinoids, or vitamin K antagonists (VKAs) to prevent recurrent ischaemic stroke. Randomised controlled trials have subsequently shown that direct oral anticoagulants (DOACs; ie, apixaban, dabigatran, edoxaban, and rivaroxaban) are at least as effective as VKAs in primary and secondary prevention of atrial fibrillation-related ischaemic stroke, with around half the risk of intracranial haemorrhage. However, none of these DOAC trials included patients who had experienced ischaemic stroke recently (within the first few weeks). Clinicians therefore remain uncertain regarding when to commence DOAC administration after acute ischaemic stroke in patients with atrial fibrillation.Recent developmentsProspective observational studies and two small randomised trials have investigated the risks and benefits of early DOAC-administration initiation (most with a median delay of 3-5 days) in mild-to-moderate atrial fibrillation-associated ischaemic stroke. These studies reported that early DOAC treatment was associated with a low frequency of clinically symptomatic intracranial haemorrhage or surrogate haemorrhagic lesions on MRI scans, whereas later DOAC-administration initiation (ie, >7 days or >14 days after index stroke) was associated with an increased frequency of recurrent ischaemic stroke. WHERE NEXT?: Adequately powered randomised controlled trials comparing early to later oral anticoagulation with DOACs in ischaemic stroke associated with atrial fibrillation are justified to confirm the acceptable safety and efficacy of this strategy. Four such randomised controlled trials (collectively planned to include around 9000 participants) are underway, either using single cutoff timepoints for early versus late DOAC-administration initiation, or selecting DOAC-administration timing according to the severity and imaging features of the ischaemic stroke. The results of these trials should help to establish the optimal timing to initiate DOAC administration after recent ischaemic stroke and whether the timing should differ according to stroke severity. Results of these trials are expected from 2021.

Project description:BackgroundCerebral microbleeds are a potential neuroimaging biomarker of cerebral small vessel diseases that are prone to intracranial bleeding. We aimed to determine whether presence of cerebral microbleeds can identify patients at high risk of symptomatic intracranial haemorrhage when anticoagulated for atrial fibrillation after recent ischaemic stroke or transient ischaemic attack.MethodsOur observational, multicentre, prospective inception cohort study recruited adults aged 18 years or older from 79 hospitals in the UK and one in the Netherlands with atrial fibrillation and recent acute ischaemic stroke or transient ischaemic attack, treated with a vitamin K antagonist or direct oral anticoagulant, and followed up for 24 months using general practitioner and patient postal questionnaires, telephone interviews, hospital visits, and National Health Service digital data on hospital admissions or death. We excluded patients if they could not undergo MRI, had a definite contraindication to anticoagulation, or had previously received therapeutic anticoagulation. The primary outcome was symptomatic intracranial haemorrhage occurring at any time before the final follow-up at 24 months. The log-rank test was used to compare rates of intracranial haemorrhage between those with and without cerebral microbleeds. We developed two prediction models using Cox regression: first, including all predictors associated with intracranial haemorrhage at the 20% level in univariable analysis; and second, including cerebral microbleed presence and HAS-BLED score. We then compared these with the HAS-BLED score alone. This study is registered with ClinicalTrials.gov, number NCT02513316.FindingsBetween Aug 4, 2011, and July 31, 2015, we recruited 1490 participants of whom follow-up data were available for 1447 (97%), over a mean period of 850 days (SD 373; 3366 patient-years). The symptomatic intracranial haemorrhage rate in patients with cerebral microbleeds was 9·8 per 1000 patient-years (95% CI 4·0-20·3) compared with 2·6 per 1000 patient-years (95% CI 1·1-5·4) in those without cerebral microbleeds (adjusted hazard ratio 3·67, 95% CI 1·27-10·60). Compared with the HAS-BLED score alone (C-index 0·41, 95% CI 0·29-0·53), models including cerebral microbleeds and HAS-BLED (0·66, 0·53-0·80) and cerebral microbleeds, diabetes, anticoagulant type, and HAS-BLED (0·74, 0·60-0·88) predicted symptomatic intracranial haemorrhage significantly better (difference in C-index 0·25, 95% CI 0·07-0·43, p=0·0065; and 0·33, 0·14-0·51, p=0·00059, respectively).InterpretationIn patients with atrial fibrillation anticoagulated after recent ischaemic stroke or transient ischaemic attack, cerebral microbleed presence is independently associated with symptomatic intracranial haemorrhage risk and could be used to inform anticoagulation decisions. Large-scale collaborative observational cohort analyses are needed to refine and validate intracranial haemorrhage risk scores incorporating cerebral microbleeds to identify patients at risk of net harm from oral anticoagulation.FundingThe Stroke Association and the British Heart Foundation.

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Potential missed opportunities to prevent ischaemic stroke: prospective multicentre cohort study of atrial fibrillation-associated ischaemic stroke and TIA.

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Potential missed opportunities to prevent ischaemic stroke: prospective multicentre cohort study of atrial fibrillation-associated ischaemic stroke and TIA.

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