Long-term colchicine for the prevention of vascular recurrent events in non-cardioembolic stroke (CONVINCE): a randomised controlled trial.

BACKGROUND: Anti-inflammatory therapy with long-term colchicine prevented vascular recurrence in coronary disease. Unlike coronary disease, which is typically caused by atherosclerosis, ischaemic stroke is caused by diverse mechanisms including atherosclerosis and small vessel disease or is frequently due to an unknown cause. We aimed to investigate the hypothesis that long-term colchicine would reduce recurrent events after ischaemic stroke. METHODS: We did a randomised, parallel-group, open-label, blinded endpoint assessed trial comparing long-term colchicine (0·5 mg orally per day) plus guideline-based usual care with usual care only. Hospital-based patients with non-severe, non-cardioembolic ischaemic stroke or high-risk transient ischaemic attack were eligible. The primary endpoint was a composite of first fatal or non-fatal recurrent ischaemic stroke, myocardial infarction, cardiac arrest, or hospitalisation (defined as an admission to an inpatient unit or a visit to an emergency department that resulted in at least a 24 h stay [or a change in calendar date if the hospital admission or discharge times were not available]) for unstable angina. The p value for significance was 0·048 to adjust for two prespecified interim analyses conducted by the data monitoring committee, for which the steering committee and trial investigators remained blinded. The trial was registered at ClinicalTrials.gov (NCT02898610) and is completed. FINDINGS: 3154 patients were randomly assigned between Dec 19, 2016, and Nov 21, 2022, with the last follow-up on Jan 31, 2024. The trial finished before the anticipated number of outcomes was accrued (367 outcomes planned) due to budget constraints attributable to the COVID-19 pandemic. Ten patients withdrew consent for analysis of their data, leaving 3144 patients in the intention-to-treat analysis: 1569 (colchicine and usual care) and 1575 (usual care alone). A primary endpoint occurred in 338 patients, 153 (9·8%) of 1569 patients allocated to colchicine and usual care and 185 (11·7%) of 1575 patients allocated to usual care alone (incidence rates 3·32 vs 3·92 per 100 person-years, hazard ratio 0·84; 95% CI 0·68-1·05, p=0·12). Although no between-group difference in C-reactive protein (CRP) was observed at baseline, patients treated with colchicine had lower CRP at 28 days and at 1, 2, and 3 years (p<0·05 for all timepoints). The rates of serious adverse events were similar in both groups. INTERPRETATION: Although no statistically significant benefit was observed on the primary intention-to-treat analysis, the findings provide new evidence supporting the rationale for anti-inflammatory therapy in further randomised trials. FUNDING: Health Research Board Ireland, Deutsche Forschungsgemeinschaft (German Research Foundation), and Fonds Wetenschappelijk Onderzoek Vlaanderen (Research Foundation Flanders), Belgium.

Investigating secondary hypertension in cerebrovascular disease.

Hypertension is the leading cause of stroke in the UK and worldwide. In recent years, stroke incidence has increased by 30%-41.5% in people aged under 64 years, with the prevalence of hypertension increasing by 4%-11%. Given that 5%-10% of people with hypertension in the general population have an underlying cause for their elevated blood pressure, it is important that all clinicians should maintain a high clinical suspicion for secondary hypertension. This review provides a clinical perspective of when to consider the underlying causes of secondary hypertension, with investigation algorithms for patients presenting with stroke and hypertension. Early involvement of hypertension specialist services is important to identify secondary causes of hypertension, as its effective control reduces cardiovascular-associated morbidity.

Management of carotid atherosclerosis in stroke.

Internal carotid artery atherosclerosis is a major risk factor for stroke, accounting for 15-20% of ischaemic strokes. Revascularisation procedures-either carotid endarterectomy or carotid artery stenting-can reduce the risk of stroke for those with significant (>50%) luminal stenosis but particularly for those with more severe (70-99%) stenosis. However, advances in medical pharmacotherapy have implications for the relative benefit from surgery for symptomatic carotid atherosclerosis, as well as our approach to asymptomatic disease. This review considers the evidence underpinning the current medical and surgical management of symptomatic carotid atherosclerosis, the importance of factors beyond the degree of luminal stenosis, and developments in therapeutic strategies. We also discuss the importance of non-stenotic but high-risk carotid atherosclerotic plaques on the cause of stroke, and their implications for clinical practice.

Pre-Stroke Frailty and Outcomes following Percutaneous Endoscopic Gastrostomy Tube Insertion.

BACKGROUND: Frailty is common in stroke, where it exerts disease- and treatment-modifying effects. However, there has been little work evaluating how frailty influences outcomes after percutaneous endoscopic gastrostomy (PEG) tube insertion. This study investigates the relationship between pre-stroke frailty and one-year mortality following PEG insertion. METHODS: A pre-stroke frailty index (FI) was calculated for individuals with post-stroke dysphagia who underwent PEG insertion between March 2019 and February 2021. Mortality was recorded at one year, as well as instances of post-PEG pneumonia and discharge destination. RESULTS: Twenty-nine individuals underwent PEG insertion, eleven (37.9%) of whom died in the subsequent year. The mean (SD) FI for those who survived was 0.10 (0.09), compared to 0.27 (0.19) for those who died (p = 0.02). This remained significant after adjustment for age and sex, with each 0.1 increase in the FI independently associated with an increased odds of one-year mortality (aOR 1.39, 95% CI 1.17-1.67). There was no association between frailty and post-PEG pneumonia (0.12 (0.21) in those who aspirated versus 0.11 (0.18) in those who did not, p = 0.75). CONCLUSIONS: Pre-stroke frailty is associated with increased one-year mortality after PEG, a finding that may help inform shared clinical decision-making in complex decisions regarding PEG feeding.

Hyperacute stroke thrombolysis via telemedicine: a multicentre study of performance, safety and clinical efficacy.

OBJECTIVES: Timely thrombolysis of ischaemic stroke improves functional recovery, yet its delivery nationally is challenging due to shortages in the stroke specialist workforce and large geographical areas. One solution is remote stroke specialist input to regional centres via telemedicine. This study evaluates the usage and key metrics of performance of the East of England Stroke Telemedicine Partnership-the largest telestroke service in the UK-in providing hyperacute stroke care. DESIGN: Prospective observational study. SETTING: The East of England Stroke Telemedicine Partnership provides a horizontal 'hubless' model of out-of-hours hyperacute stroke care to a population of 6.2 million across a 7500 square mile semirural region. PARTICIPANTS: All (2709) telestroke consultations between 1 January 2014 and 31 December 2019. MAIN OUTCOME MEASURES: Thrombolysis decision, pre-thrombolysis and post-thrombolysis stroke severity (National Institutes of Health Stroke Scale, NIHSS), haemorrhagic complications, and hyperacute pathway timings. RESULTS: Over the period, 1149 (42.4%) individuals were thrombolysed. Thrombolysis rates increased from 147/379 (38.8%) in 2014 to 225/490 (45.9%) in 2019. Median (IQR) pre-thrombolysis NIHSS was 10 (6-17), reducing to 6 (2-14) 24-hour post-thrombolysis (p<0.001). Post-thrombolysis haemorrhage occurred in 27 cases (2.3%). Over the period, median (IQR) door-to-needle time reduced from 85 (65-108) min to 68 (55-97.5) min (p<0.01), driven by improved imaging-to-needle times from 52.5 (38-72.25) min to 42 (30.5-62.5) min (p<0.01). However, the same period saw an increase in median onset-to-hospital arrival time from 77.5 (60-109.25) min to 95 (70-135) min (p<0.001). CONCLUSIONS: The results from this large hyperacute telestroke cohort indicate two important points for clinical practice. First, telemedicine via a hubless horizontal model provides a clinically effective and safe method for delivering hyperacute stroke thrombolysis. Second, improved door-to-needle times were offset by a concerning rise in prehospital timings. These findings indicate that although telemedicine may benefit in-hospital hyperacute stroke care, improvements across the whole stroke pathway are essential.