Changes in anticoagulation practice in subjects admitted with stroke associated with atrial fibrillation, following introduction of direct oral anticoagulants over 2013-2021.

BACKGROUND: The adoption of direct oral anticoagulants (DOACs) has changed practice in prevention of stroke in atrial fibrillation (AF). We used Irish data national data on stroke and anticoagulation therapy over 9 years to investigate changes in anticoagulation practice and potential consequences on stroke prevalence and thrombolysis. METHODS: AF, anticoagulation, thrombolysis, and stroke data from the Irish National Audit of Stroke (INAS) 2013-2021 were reviewed. The proportion of patients with ischemic stroke (IS) and intracerebral hemorrhage (IH) with known AF admitted on anticoagulation was determined. Effects on age distribution in the population and thrombolysis practice were assessed. RESULTS: AF data were available on 34,630 of 35,241 individuals (98.3%) included in INAS; median age was 74 years and 56% were male. AF was found in 10,016 (28.9%, 9059 IS, 957 IH). 6313 had known AF prior to stroke (63.1%). The proportion all total IS due to AF decreased by 15.3% (31.3%-26.5%, chi-square = 24.6, p < 0.0001). The proportion of IH did not change significantly (21.6%-20.2%, chi-square = 1.8, p = 0.18). Over the 9 years, 3875 (38.6%) of the subjects with AF were recorded as receiving anticoagulants at admission. In 2013, 4.4% of AF-associated strokes were admitted on a DOAC and 21.4% on warfarin; by 2021, 44.1% were receiving a DOAC and 6.2% warfarin. There was a strong inverse correlation between the proportion of anticoagulated stroke patients and the total proportion of AF-associated strokes over time (r = -0.82, p = 0.006). In contrast, no correlation was found between increasing DOAC usage and IH (r = 0.14, p = 0.71). Increased anticoagulation usage correlated with a reduction in patients ⩾ 80 years (r = -0.83, p = 0.006) and also correlated with a relative reduction of 30.1% in subjects thrombolysed <4 h from onset (r = -0.89, p = 0.001). CONCLUSION: DOACs have led to increased use of anticoagulation, but warfarin use fell by two-thirds. There has been a reduction in the proportion of AF-associated IS without a noticeable increase in IH. Increased anticoagulation correlated with reduced numbers of strokes in those >80 years and in the proportion of patients thrombolysed.

Symptomatic Carotid Atheroma Inflammation Lumen-stenosis score compared with Oxford and Essen risk scores to predict recurrent stroke in symptomatic carotid stenosis.

BACKGROUND: The Oxford Carotid Stenosis tool (OCST) and Essen Stroke Risk Score (ESRS) are validated to predict recurrent stroke in patients with and without carotid stenosis. The Symptomatic Carotid Atheroma Inflammation Lumen stenosis (SCAIL) score combines stenosis and plaque inflammation on fluorodeoxyglucose positron-emission tomography (18FDG-PET). We compared SCAIL with OCST and ESRS to predict ipsilateral stroke recurrence in symptomatic carotid stenosis. PATIENTS AND METHODS: We pooled three prospective cohort studies of patients with recent (<30 days) non-severe ischaemic stroke/TIA and internal carotid artery stenosis (>50%). All patients had carotid 18FDG-PET/CT angiography and late follow-up, with censoring at carotid revascularisation. RESULTS: Of 212 included patients, 16 post-PET ipsilateral recurrent strokes occurred in 343 patient-years follow-up (median 42 days (IQR 13-815)).Baseline SCAIL predicted recurrent stroke (unadjusted hazard ratio [HR] 1.96, CI 1.20-3.22, p = 0.007, adjusted HR 2.37, CI 1.31-4.29, p = 0.004). The HR for OCST was 0.996 (CI 0.987-1.006, p = 0.49) and for ESRS was 1.26 (CI 0.87-1.82, p = 0.23) (all per 1-point score increase). C-statistics were: SCAIL 0.66 (CI 0.51-0.80), OCST 0.52 (CI 0.40-0.64), ESRS 0.61 (CI 0.48-0.74). Compared with ESRS, addition of plaque inflammation (SUVmax) to ESRS improved risk prediction when analysed continuously (HR 1.51, CI 1.05-2.16, p = 0.03) and categorically (ptrend = 0.005 for risk increase across groups; HR 3.31, CI 1.42-7.72, p = 0.006; net reclassification improvement 10%). Findings were unchanged by further addition of carotid stenosis. CONCLUSIONS: SCAIL predicted recurrent stroke, had discrimination better than chance, and improved the prognostic utility of ESRS, suggesting that measuring plaque inflammation may improve risk stratification in carotid stenosis.

Noise and transient ischaemic attacks - A challenge?

Consistency in medical decision-making is ideally expected. This includes consistency between different clinicians so that the same patient will receive the same diagnosis regardless of the assessing clinician. It also encompasses reliability as an individual clinician meaning at any given time or context, we apply the same process and principles to ensure the decisions we make do not deviate significantly from our peers or indeed our own past decisions. However, consistency in decision-making can be challenged when working within a busy healthcare system. We discuss the concept of 'noise' and explore how it affects decision-making in acute presentations of transient neurology where doctors can differ in terms of their diagnostic decisions.

Carotid endarterectomy for symptomatic carotid artery stenosis in a patient who presented with psychosis.

Acute psychosis is an unusual presentation of stroke particularly in a patient with no history of psychiatric illness. We report a case where an elderly male patient with self-inflicted injuries caused by acute psychosis. The investigation confirmed an acute left hemispherical stroke associated with a high-grade left internal carotid artery stenosis. The patient underwent a successful left carotid endarterectomy. His psychotic symptoms resolved and he was discharged home without the need for neuroleptic medication.

Dose-Dependent Association of Inflammatory Cytokines with Carotid Atherosclerosis in Transient Ischaemic Attack: Implications for Clinical Trials.

INTRODUCTION: The 5-year recurrence risk after ischaemic stroke and transient ischaemic attack (TIA) is 25-30%. Although inflammation may be a target for prevention trials, the contribution of plaque inflammation to acute cerebrovascular events remains unclear. We investigated the association of acute inflammatory cytokines and high-sensitivity C-reactive protein (CRP) with recently symptomatic carotid atherosclerosis in a prospective cohort study. METHODS: Blood and Imaging markers of TIA BIO-TIA) is a multicentre prospective study of imaging and inflammatory markers in patients with TIA. Exclusion criteria were infection and other co-morbid illnesses associated with inflammation. CRP and serum cytokines (interleukin [IL]-6, IL-1ß, IL-8, IL-10, IL-12, interferon-γ [IFN-γ] and tumour necrosis factor-α [TNF-α]) were measured. All patients had carotid imaging. RESULTS: Two hundred and thirty-eight TIA cases and 64 controls (TIA mimics) were included. Forty-nine (20.6%) cases had symptomatic internal carotid artery stenosis. Pro-inflammatory cytokine levels increased in a dose-dependent manner across controls, TIA without carotid stenosis (CS), and TIA with CS (IL-1ß, ptrend = 0.03; IL-6, ptrend < 0.0001; IL-8, ptrend = 0.01; interferon (IFN)-γ, ptrend = 0.005; TNF-α, ptrend = 0.003). Results were unchanged when DWI-positive cases were excluded. On multivariable linear regression, only age (p = 0.01) and CS (p = 0.04) independently predicted log-IL-6. On multivariable Cox regression, CRP was the only independent predictor of 90-day stroke recurrence (adjusted hazard ratio per 1-unit increase 1.03 [95% CI: 1.01-1.05], p = 0.003). CONCLUSION: Symptomatic carotid atherosclerosis was associated with elevated cytokines in TIA patients after controlling for other sources of inflammation. High-sensitivity CRP was associated with recurrent ischaemic stroke at 90 days. These findings implicate acute plaque inflammation in the pathogenesis of cerebral thromboembolism and support a rationale for randomized trials of anti-inflammatory therapy for stroke patients, who were excluded from coronary trials.

Carotid Plaque Inflammation Imaged by PET and Prediction of Recurrent Stroke at 5 Years.

BACKGROUND AND OBJECTIVES: To determine whether carotid plaque inflammation identified by 18F-fluorodeoxyglucose (18FDG)-PET is associated with late (5-year) recurrent stroke. METHODS: We did an individual-participant data pooled analysis of 3 prospective studies with near-identical study methods. Eligible patients had recent nonsevere (modified Rankin Scale score ≤3) ischemic stroke/TIA and ipsilateral carotid stenosis (50%-99%). Participants underwent carotid 18FDG-PET/CT angiography ≤14 days after recruitment. 18FDG uptake was expressed as maximum standardized uptake value (SUVmax) in the axial single hottest slice of symptomatic plaque. We calculated the previously validated Symptomatic Carotid Atheroma Inflammation Lumen-Stenosis (SCAIL) score, which incorporates a measure of stenosis severity and 18FDG uptake. The primary outcome was 5-year recurrent ipsilateral ischemic stroke after PET imaging. RESULTS: Of 183 eligible patients, 181 patients completed follow-up (98.9%). The median duration of follow-up was 4.9 years (interquartile range 3.3-6.4 years, cumulative follow-up period 901.8 patient-years). After PET imaging, 17 patients had a recurrent ipsilateral ischemic strokes at 5 years (recurrence rate 9.4%, 95% confidence interval [CI] 5.6%-14.6%). Baseline plaque SUVmax independently predicted 5-year ipsilateral recurrent stroke after adjustment for age, sex, carotid revascularization, stenosis severity, NIH Stroke Scale score, and diabetes mellitus (adjusted hazard ratio [HR] 1.98, 95% CI 1.10-3.56, p = 0.02 per 1-g/mL increase in SUVmax). On multivariable Cox regression, SCAIL score predicted 5-year ipsilateral stroke (adjusted HR 2.73 per 1-point increase, 95% CI 1.52-4.90, p = 0.001). DISCUSSION: Plaque inflammation-related 18FDG uptake improved identification of 5-year recurrent ipsilateral ischemic stroke. Addition of plaque inflammation to current selection strategies may target patients most likely to have late and early benefit from carotid revascularization. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in individuals with recent ischemic stroke/TIA and ipsilateral carotid stenosis, carotid plaque inflammation-related 18FDG uptake on PET/CT angiography was associated with 5-year recurrent ipsilateral stroke.

Cohort profile: BIOVASC-late, a prospective multicentred study of imaging and blood biomarkers of carotid plaque inflammation and risk of late vascular recurrence after non-severe stroke in Ireland.

PURPOSE: Inflammation is important in stroke. Anti-inflammatory therapy reduces vascular events in coronary patients. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) identifies plaque inflammation-related metabolism. However, long-term prospective cohort studies investigating the association between carotid plaque inflammation, identified on 18F-FDG PET and the risk of recurrent vascular events, have not yet been undertaken in patients with stroke. PARTICIPANTS: The Biomarkers Imaging Vulnerable Atherosclerosis in Symptomatic Carotid disease (BIOVASC) study and Dublin Carotid Atherosclerosis Study (DUCASS) are two prospective multicentred observational cohort studies, employing near-identical methodologies, which recruited 285 patients between 2008 and 2016 with non-severe stroke/transient ischaemic attack and ipsilateral carotid stenosis (50%-99%). Patients underwent coregistered carotid 18F-FDG PET/CT angiography and phlebotomy for measurement of inflammatory cytokines. Plaque 18F-FDG-uptake is expressed as maximum standardised uptake value (SUVmax) and tissue-to-background ratio. The BIOVASC-Late study is a follow-up study (median 7 years) of patients recruited to the DUCASS/BIOVASC cohorts. FINDINGS TO DATE: We have reported that 18F-FDG-uptake in atherosclerotic plaques of patients with symptomatic carotid stenosis predicts early recurrent stroke, independent of luminal narrowing. The incorporation of 18F-FDG plaque uptake into a clinical prediction model also improves discrimination of early recurrent stroke, when compared with risk stratification by luminal stenosis alone. However, the relationship between 18F-FDG-uptake and late vascular events has not been investigated to date. FUTURE PLANS: The primary aim of BIOVASC-Late is to investigate the association between SUVmax in symptomatic 'culprit' carotid plaque (as a marker of systemic inflammatory atherosclerosis) and the composite outcome of any late major vascular event (recurrent ischaemic stroke, coronary event or vascular death). Secondary aims are to investigate associations between: (1) SUVmax in symptomatic plaque, and individual vascular endpoints (2) SUVmax in asymptomatic contralateral carotid plaque and SUVmax in ipsilateral symptomatic plaque (3) SUVmax in asymptomatic carotid plaque and major vascular events (4) inflammatory cytokines and vascular events.

Early repatriation post-thrombectomy: a model of care which maximises the capacity of a stroke network to treat patients with large vessel ischaemic stroke.

BACKGROUND AND PURPOSE: Healthcare systems are challenged to provide access to thrombectomy in acute stroke patients. Either the "drip and ship" or "mothership" models result in increased numbers of patients in the endovascular stroke centre (ESC). We describe our approach for a "drip, ship, retrieve and leave" model repatriating patients immediately or within 24 hours of thrombectomy. METHODS: We included consecutive patients who underwent thrombectomy from January 2016 to June 2018. Patients from local region primary stroke centres (PSC) are immediately repatriated and those from remote region PSCs are admitted for 24 hours before repatriation. Key parameters recorded included clinical, radiological and timeline data as well as 90-day modified Rankin Scale (mRS). Patients who stayed beyond the intended time period in the ESC were analysed. RESULTS: From January 2016 to June 2018, 435 patients were transferred, with 352 patients in the local region group and 83 in the remote region group. The median NIHSS was 16 with a median ASPECTS of 9. Good functional outcome was seen in 47% of patients with a mortality rate of 19%. The local region group that were repatriated at the intended time period had a 90-day mRS 0-2 of 47% compared with 20% of those admitted to the ESC (P=0.006). Mortality rates were 20% and 27% respectively (P=0.377). The remote region group, repatriated at 24 hours' post-emergency endovascular thrombectomy had 90-day mRS 0-2 of 65% compared with 41% in the group admitted (P=0.042). Mortality rates were 4% and 22% respectively (P=0.007). CONCLUSION: This model enables the treatment of large numbers of patients with large vessel occlusion acute ischaemic stroke with thrombectomy within a national stroke service and system of care which would not otherwise be facilitated.

Effects of diagnostic uncertainty and misclassification on hospital performance indicators for acute stroke care.

The Stroke Improvement National Audit Programme (SINAP), now replaced by the Sentinel Stroke National Audit Programme, was established to provide comparative data on hospital performance indicators for stroke, but comparisons are only valid if case ascertainment is complete. In Gateshead we compared initial results from SINAP with those from a pre-existing hospital stroke register, which ran independently for 11 months after SINAP's introduction in 2010, as well as with Hospital Episode Statistics (HES) data. Of 315 confirmed acute stroke cases identified from the three combined data sources, 96 (30%) were omitted from SINAP and 51 (16%) were missed by HES. Of 478 suspected strokes in the combined datasets, 214 were either misclassified by HES or remained with uncertain diagnosis. These patients had much lower mortality and shorter hospital stays than those with confirmed stroke. This diagnostic uncertainty could be an important source of uncontrolled variation in, or even a potential target for manipulation of, hospital performance indicators for stroke.

Polymyalgia rheumatica and temporal arteritis: evidence and guidelines for diagnosis and management in older people.

Polymyalgia rheumatica and temporal arteritis commonly present for the first time in older people. Guidelines for diagnosis, investigation and management are available but have largely been developed by rheumatologists from studies where older people have been excluded. It is not clear whether geriatricians care for a group of patients with different clinical presentations compared to those under the care of other clinicians. There is a need for further prospective studies and randomised controlled trials to clarify a host of outstanding issues to improve the care of older people with polymyalgia rheumatica and temporal arteritis.