Functional Outcomes at 90 Days in Octogenarians Undergoing Thrombectomy for Acute Ischemic Stroke: A Prospective Cohort Study and Meta-Analysis

Background: Elderly patients account for 30% of acute ischemic stroke (AIS) but are under-represented in randomized controlled trials of endovascular thrombectomy (EVT). Meta-analysis of “real world” studies evaluating 90-day outcomes in elderly patients ≥80 years have been limited to small numbers undergoing EVT with older generation devices.Methods: A retrospective analysis of 181 prospectively collected patients who received EVT for anterior circulation AIS at an Australian center over 2.5-years. The study aims to determine (i) 90-day functional outcomes (modified Rankin Scale mRS 0–2) in patients ≥80 vs. <80 years, (ii) the interaction of prognostic factors and age and (iii) compare our data to those previously reported using a meta-analysis of outcomes in observational studies using second generation thrombectomy devices.Results: We analyzed 2,387 patients (≥80 years, n = 649; <80 years, n = 1,738) from 14 studies including our study (≥80 years, n = 71; <80 years, n = 110). Twenty-eight percent of our and 30% of the meta-analysis elderly cohort achieved good 90-day mRS compared to 55 and 52%, respectively of younger patients (p < 0.001). Twenty-seven percent of our and 26% of the meta-analysis elderly cohort died compared to 16% (p = 0.07) and 15% (p < 0.0001), respectively of younger patients. Baseline NIHSS≥16 correlated with poor prognosis in elderly (OR 16.4; 95% CI 4.49–59.91, p < 0.001) and younger (OR 8.73;95% CI 3.35–22.80, p < 0.001) patients. Prior rt-PA was associated with favorable outcome in younger (OR 2.90; 95%CI 1.29–6.52, p = 0.01) patients only.Conclusion: EVT has less favorable outcomes in elderly patients. However, results are better than outcomes in historical controls not treated with thrombectomy providing further support for EVT in the elderly

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Review of CT perfusion and current applications in posterior circulation stroke

Acute ischemic stroke is a leading cause of death and disability. Treatment efficacy is highly time-dependent. Approximately 20% of acute ischaemic stroke occurs in the posterior circulation. Clinical presentation of posterior circulation stroke is subtle. Diagnosis is often delayed and frequently missed. CT perfusion has improved diagnostic accuracy and been integral to guiding acute therapy in patients with anterior circulation stroke. There are limited studies assessing the role of CT perfusion in posterior circulation stroke. This review provides a reference for interpretation of CT perfusion and summarises current evidence relating to applications in acute posterior circulation stroke

Comparison of functional outcomes after endovascular thrombectomy in patients with and without atrial fibrillation

Aim: Patients with atrial fibrillation (AF) are over-represented in endovascular thrombectomy (EVT) populations, due to a high prevalence of large vessel occlusions (LVO) and contraindication to intravenous thrombolysis. This study aimed to: (1) compare 90-day functional outcomes [modified Rankin Score (mRS) 0-2] and mortality in AF vs. non-AF patients receiving EVT; (2) compare 90-day functional outcomes and mortality in AF patients on therapeutic vs. non-therapeutic anticoagulation receiving EVT; and (3) identify factors influencing outcomes in AF patients receiving EVT.Methods: A retrospective analysis of 394 consecutive patients who received EVT for anterior cerebral circulation LVO at an Australian comprehensive stroke center was performed. The main outcome measures [90-day dichotomized mRS (0-2 good; 3-6 poor functional outcome) and mortality] were compared between AF and non-AF patients, as well as between therapeutic and non-therapeutic anticoagulation cohorts.Results: In total, 171 (49%) EVT patients had AF. Patients with AF were older, had higher NIHSS, and had lower rates of thrombolysis administration. AF patients showed improved 90-day mRS on multivariate analysis [aOR 1.988 (1.167-3.387)], with similar symptomatic intracranial hemorrhage (sICH) [aOR 0.364 (0.064-2.086)] and mortality [aOR 1.454 (0.785-2.696)]. There was no difference in 90-day mRS [aOR 1.402 (0.625-3.145)], successful reperfusion rates [aOR 3.761 (0.661-21.410)], or mortality [aOR 1.077 (0.429-2.705)] between AF patients on therapeutic vs. non-therapeutic anticoagulation. In patients with AF, advancing age and higher NIHSS were independent predictors of worse 90-day functional outcome (OR = 1.045, P = 0.020; OR = 1.086, P = 0.001) and mortality (OR = 1.138, P &lt; 0.001; OR = 1.107, P = 0.002). On multivariate analysis, thrombolysis administration improved mortality (OR = 0.215, P = 0.016) but not functional outcomes.Conclusion: Patients with AF showed improved 90-day functional outcome, with similar mortality and sICH, after EVT. Therapeutic anticoagulation did not adversely influence EVT outcomes

Clarion call for histopathological clot analysis in "cryptogenic" ischemic stroke : implications for diagnosis and treatment

Diagnosis, treatment, and secondary management of cryptogenic stroke patients pose a formidable challenge. The scenario is further complicated in patients with native and prosthetic valvular heart disease. We present a case study of a 36-year-old man who received intravenous thrombolysis (IV-tPA) and endovascular thrombectomy (EVT) for presumed "cryptogenic" complete middle cerebral artery infarction who made a surprisingly excellent clinical recovery despite poor baseline and postintervention neuroimaging. Retrospective gram stain of his clot confirmed a diagnosis of infective endocarditis. This raises an important issue regarding need for more routine histopathological analysis of clot retrieved after EVT in "cryptogenic" stroke patients particularly those with valvular heart disease