Stroke Risk and Risk Factors in Patients With Central Retinal Artery Occlusion.

PURPOSE: Central retinal artery occlusion (CRAO) is mechanistically similar to a stroke. Current guidelines recommend a standardized and systematic evaluation of risk factors for patients who have had a stroke. This study evaluates the yield of this evaluation in patients with CRAO and frequency of stroke in this population. DESIGN: Cohort study. METHODS: We evaluated the diagnostic yield of an expedited inpatient evaluation of cerebrovascular risk factors in a cohort of patients presenting with an acute CRAO within the period from 2009 to 2017 at an academic hospital. Vital signs and laboratory parameters, including low-density lipoprotein level, hemoglobin A1c fraction, erythrocyte sedimentation rate, C-reactive protein level, platelet count, and troponin level, were collected. Echocardiography, cardiac telemetry, magnetic resonance imaging (MRI), and cerebrovascular imaging were obtained to screen for strokes and vascular risk factors. All new diagnoses and clinical treatments stemming from the inpatient evaluation were documented. Outcomes included the frequency of stroke on MRI, hypertensive emergency, critical carotid disease, or critical cardiac disease, including high-grade valvular lesions, new myocardial infarction, or arrhythmias. We documented the frequency of a change in medication, acute surgical intervention, or new diagnosis of systemic disease as a result of the inpatient evaluation. Finally, we evaluated the rate of symptomatic stroke, myocardial infarct, and death risk in the 24 months after CRAO. RESULTS: In this cohort of 103 patients with CRAO and systematic risk factor screening, 36.7% of patients had critical carotid disease, 37.3% had coincident acute stroke, 33.0% presented with hypertensive emergency, 20.0% had a myocardial infarction or critical structural cardiac disease, 25% underwent an urgent surgical intervention, and 93% had a change in medication as a result of the inpatient evaluation. Patients with CRAO had similar risk of subsequent stroke, myocardial infarction, and death as patients with high-risk transient ischemic attack. CONCLUSIONS: Patients with CRAO are at significant risk of future cardiovascular and cerebrovascular events and often have undiagnosed risk factors that may be modifiable

A multicenter study of the safety and effectiveness of mechanical thrombectomy for patients with acute ischemic stroke not meeting top-tier evidence criteria

Background: While mechanical thrombectomy (MT) has become the standard of care for patients with acute ischemic stroke (AIS) with emergent large-vessel occlusions (ELVO), recently published guidelines appropriately award top-tier evidence to the same selective criteria that were employed in completed clinical trials. We sought to evaluate the safety and effectiveness of MT in patients with AIS with ELVO who do not meet top-tier evidence criteria (TTEC). Methods: We conducted an observational study on consecutive patients with AIS with ELVO who underwent MT at six high-volume endovascular centers. Standard safety outcomes (3-month mortality, symptomatic intracranial hemorrhage) and effectiveness outcomes (3-month functional independence: modified Rankin Scale scores of 0–2) were compared between patients meeting and failing TTEC. Results: The sample consisted of 349 (60%) controls fulfilling TTEC and 234 (40%) non-TTEC patients. Control patients meeting TTEC for MT tended to have higher functional independence rates at 3 months (47% vs 39%; p=0.055), while the rates of symptomatic intracerebral hemorrhage (sICH) were similar (9%) in both groups (p=0.983). In multivariable logistic regression models, adherence to TTEC for MT was not independently related to any safety outcome (sICH: OR 0.71, 95% CI 0.30 to 1.68, p=0.434; 3-month mortality: OR 1.27, 95% CI 0.69 to 2.33, p=0.448) or effectiveness outcome (3-month functional independence: OR 0.81, 95% CI 0.48 to 1.37, p=0.434; 3-month functional improvement: OR 0.73, 95% CI 0.48 to 1.11, p=0.138) after adjusting for potential confounders. Conclusions: Approximately 40% of patients with AIS with ELVO offered MT do not fulfill TTEC for MT. Patients who did not meet TTEC had high rates of good clinical outcome and low complication rates

Comparative Safety and Efficacy of Modified TICI 2b and TICI 3 Reperfusion in Acute Ischemic Strokes Treated With Mechanical Thrombectomy.

BACKGROUND: Mechanical thrombectomy (MT) is the current standard of care for acute ischemic stroke (AIS) patients with emergent large-vessel occlusions (ELVO). Successful reperfusion of ELVO is traditionally defined by modified Thrombolysis in Cerebral Infarction (mTICI) grades of 2b or 3. OBJECTIVE: To evaluate the comparative safety and efficacy of mTICI 2b and mTICI 3 reperfusion in AIS patients treated with MT. METHODS: Consecutive ELVO patients who underwent MT at 6 high-volume centers were included in this analysis. Standard safety (3-mo mortality, symptomatic intracranial hemorrhage [sICH]) and efficacy (absolute and relative reduction in NIHSS-scores during hospitalization, functional-improvement [shift analysis in mRS-scores], and functional-independence [mRS-scores of 0-2] at 3-mo) were compared between patients who had mTICI 2b and mTICI 3 reperfusion post MT. RESULTS: A total of 416 ELVO patients achieved successful reperfusion with mTICI 2b (n = 216) and mTICI 3 (n = 200) following MT. The mTICI 3 group had significantly (P \u3c .05) greater absolute (11 vs 9 points) and relative (77% vs 63%) reduction in NIHSS-scores during hospitalization, lower sICH (6% vs 12%), and higher 3-mo functional-independence (55% vs 44%) rates. Successful reperfusion with mTICI 3 was independently (P \u3c .05) associated with greater absolute and relative reduction in NIHSS-scores during hospitalization as well as higher odds of 3-mo functional improvement (common odds ratios: 1.67; 95% confidence interval: 1.10-2.56) and functional independence (odds ratio: 2.08; 95% confidence interval: 1.22-3.53) in multivariable regression models adjusting for confounders. CONCLUSION: Successful reperfusion with mTICI 3 was associated with greater neurological improvement during hospitalization and better 3-mo functional outcomes in comparison to mTICI 2b reperfusion

Comparative safety and efficacy of combined IVT and MT with direct MT in large vessel occlusion.

OBJECTIVE: In this multicenter study, we sought to evaluate comparative safety and efficacy of combined IV thrombolysis (IVT) and mechanical thrombectomy (MT) vs direct MT in emergent large vessel occlusion (ELVO) patients. METHODS: Consecutive ELVO patients treated with MT at 6 high-volume endovascular centers were evaluated. Standard safety and efficacy outcomes (successful reperfusion [modified Thrombolysis in Cerebral Infarction IIb/III], functional independence [FI] [modified Rankin Scale (mRS) score of 0-2 at 3 months], favorable functional outcome [mRS of 0-1 at 3 months], functional improvement [mRS shift by 1-point decrease in mRS score]) were compared between patients who underwent combined IVT and MT vs MT alone. Additional propensity score-matched analyses were performed. RESULTS: A total of 292 and 277 patients were treated with combination therapy and direct MT, respectively. The combination therapy group had greater functional improvement ( CONCLUSIONS: This observational study provides preliminary evidence that IVT pretreatment may improve outcomes in ELVO patients treated with MT. The question of the potential effect of IVT on ELVO patients treated with MT should be addressed with a randomized controlled trial. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for stroke patients with emergent large vessel occlusion, combined IVT and MT is superior to direct MT in improving functional outcomes

Intravenous Fibrinolysis for Central Retinal Artery Occlusion: A Cohort Study and Updated Patient-Level Meta-Analysis

BACKGROUND AND PURPOSE: Central retinal artery occlusion results in sudden, painless, usually permanent loss of vision in the affected eye. There is no proven, effective treatment to salvage visual acuity and a clear, unmet need for an effective therapy. In this work, we evaluated the efficacy of intravenous tissue-type plasminogen activator (IV alteplase) in a prospective cohort study and an updated systematic review and meta-analysis. METHODS: We enrolled consecutive patients with acute central retinal artery occlusion within 48 hours of symptoms onset and with a visual acuity of \u3c20/200 from January 2009 until May 2019. The primary outcomes were safety and functional visual acuity recovery. We compared rates of visual recovery between those treated with alteplase within 4.5 hours of symptom onset to those who did not receive alteplase (including an analysis restricted to untreated patients presenting within the window for treatment). We incorporated these results into an updated systematic review and patient-level meta-analysis. RESULTS: We enrolled 112 patients, of whom 25 (22.3% of the cohort) were treated with IV alteplase. One patient had an asymptomatic intracerebral hemorrhage after IV alteplase treatment. Forty-four percent of alteplase-treated patients had recovery of visual acuity when treated within 4.5 hours versus 13.1% of those not treated with alteplase (P=0.003) and 11.6% of those presenting within 4 hours who did not receive alteplase (P=0.03). Our updated patient-level meta-analysis of 238 patients included 67 patients treated with alteplase within 4.5 hours since time last known well with a recovery rate of 37.3%. This favorably compares with a 17.7% recovery rate in those without treatment. In linear regression, earlier treatment correlated with a higher rate of visual recovery (P=0.01). CONCLUSIONS: This study showed that the administration of intravenous alteplase within 4.5 hours of symptom onset is associated with a higher likelihood of a favorable visual outcome for acute central retinal artery occlusion. Our results strongly support proceeding to a randomized, placebo-controlled clinical trial

Anticoagulation Timing in Cardioembolic Stroke and Recurrent Event Risk.

OBJECTIVES: Guidelines recommend to initiate anticoagulation within 4-14 days after cardioembolic stroke. Data supporting this did not account for key factors potentially affecting the decision to initiate anticoagulation such as infarct size, hemorrhagic transformation, or high risk features on echocardiography. METHODS: We pooled data from stroke registries of 8 comprehensive stroke centers across the United States. We included consecutive patients admitted with ischemic stroke and atrial fibrillation. The primary predictor was timing of initiating anticoagulation (0-3 days, 4-14 days, or >14 days) and outcomes were recurrent stroke/TIA/systemic embolism, symptomatic intracerebral hemorrhage (sICH), and major extracranial hemorrhage (ECH) within 90 days. RESULTS: Among 2084 patients, 1289 met the inclusion criteria. The combined endpoint occurred in 10.1% (n = 130) subjects (87 ischemic events, 20 sICH, and 29 ECH). Overall, there was no significant difference in the composite endpoint between the three groups: 0-3 days [10.3% (64/617)], 4-14 days [(9.7%) 52/535)], >14 days [10.2% (14/137), p=0.933]. In adjusted models, patients started on anticoagulation between 4-14 days did not have a lower rate of sICH (vs. 0-3 days) (OR 1.49 95% CI 0.50 – 4.43) neither did they have a lower rate of recurrent ischemic events (vs. > 14 days) (OR 0.76 95% CI 0.36 – 1.62, p = 0.482). INTERPRETATION: In this multicenter real world cohort, the recommended (4-14 days) time frame to start oral anticoagulation was not associated with reduced ischemic and hemorrhagic outcomes. Randomized trials are required to determine the optimal timing of anticoagulation initiation

Early ischaemic and haemorrhagic complications after atrial fibrillation-related ischaemic stroke: analysis of the IAC study.

INTRODUCTION: Predictors of long-term ischemic and hemorrhagic complications in atrial fibrillation (AF) have been studied, but there is limited data on predictors of early ischemic and hemorrhagic complications after AF associated ischemic stroke. We sought to determine these predictors. METHODS: The Initiation of Anticoagulation after Cardioembolic stroke (IAC) study is a multicenter retrospective study across that pooled data from consecutive patients with ischemic stroke in the setting of AF from stroke registries across 8 comprehensive stroke centers in the United States. The co-primary outcomes were recurrent ischemic event (stroke/TIA/systemic arterial embolism) and delayed symptomatic intracranial hemorrhage (d-sICH) within 90 days. We performed univariate analyses and cox regression analyses including important predictors on univariate analyses to determine independent predictors of early ischemic events (stroke/TIA/systemic embolism) and d-sICH. RESULTS: Out of 2084 patients, 1520 patients qualified; 104 patients (6.8%) had recurrent ischemic events and 23 patients (1.5%) had d-sICH within 90 days from the index event. In cox-regression models, factors associated with a trend for recurrent ischemic events were prior stroke or TIA (HR 1.42, 0.96 – 2.10) and ipsilateral arterial stenosis with 50–99% narrowing (HR 1.54, 0.98 – 2.43). Those associated with sICH were female sex (HR 2.68, 1.06– 6.83), history of hyperlipidemia (HR 2.91, 1.08 – 7.84), and early hemorrhagic transformation (HR 5.35, 2.22 – 12.92). CONCLUSION: In patients with ischemic stroke and AF, predictors of d-sICH are different than those of recurrent ischemic events therefore recognizing these predictors may help inform early stroke versus d-sICH prevention strategies

Anticoagulation Type and Early Recurrence in Cardioembolic Stroke: The IAC Study.

BACKGROUND AND PURPOSE: In patients with acute ischemic stroke and atrial fibrillation (AF), treatment with low molecular weight heparin (LMWH) increases early hemorrhagic risk without reducing early recurrence and there is limited data comparing warfarin to direct oral anticoagulant (DOAC) therapy. We aim to compare the effects of the treatments above on the risk of 90-day recurrent ischemic events and delayed symptomatic intracranial hemorrhage (d-sICH). METHODS: We included consecutive patients with acute ischemic stroke and AF from the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study pooling data from stroke registries of 8 comprehensive stroke centers across the United States. We compared recurrent ischemic events and d-sICH between each of the following groups in separate cox-regression analyses: 1) DOAC versus warfarin and 2) Bridging with heparin/LMWH versus no bridging, adjusting for pertinent confounders to test these associations. RESULTS: We identified 1,289 patients who met the “bridging versus no bridging” analysis inclusion criteria and 1,251 patients who met the “DOAC versus warfarin” analysis inclusion criteria. In adjusted cox-regression models, bridging (versus no bridging) treatment was associated with a high risk of d-sICH (HR 2.74 95% CI 1.01 – 7.42) but a similar rate of recurrent ischemic events (HR 1.23 95% CI 0.63 – 2.40). Furthermore, DOAC (versus warfarin) treatment was associated with a lower risk of recurrent ischemic events (HR 0.51 95% CI 0.29 – 0.87) but not d-sICH (HR 0.57 95% CI 0.22 – 1.48). CONCLUSION: Our study suggests that patients with ischemic stroke and AF would benefit from the initiation of a DOAC without bridging therapy. Due to our study limitations, these findings should be interpreted with caution pending confirmation from large prospective studies