Blood Pressure Trajectory Groups and Outcome After Endovascular Thrombectomy: A Multicenter Study.

BACKGROUND: Elevated blood pressure after endovascular thrombectomy (EVT) has been associated with an increased risk of hemorrhagic transformation and poor functional outcomes. However, the optimal hemodynamic management after EVT remains unknown, and the blood pressure course in the acute phase of ischemic stroke has not been well characterized. This study aimed to identify patient subgroups with distinct blood pressure trajectories after EVT and study their association with radiographic and functional outcomes. METHODS: This multicenter retrospective cohort study included consecutive patients with anterior circulation large-vessel occlusion ischemic stroke who underwent EVT. Repeated time-stamped blood pressure data were recorded for the first 72 hours after thrombectomy. Latent variable mixture modeling was used to separate subjects into five groups with distinct postprocedural systolic blood pressure (SBP) trajectories. The primary outcome was functional status, measured on the modified Rankin Scale 90 days after stroke. Secondary outcomes included hemorrhagic transformation, symptomatic intracranial hemorrhage, and death. RESULTS: Two thousand two hundred sixty-eight patients (mean age [±SD] 69±15, mean National Institutes of Health Stroke Scale 15±7) were included in the analysis. Five distinct SBP trajectories were observed: low (18%), moderate (37%), moderate-to-high (20%), high-to-moderate (18%), and high (6%). SBP trajectory group was independently associated with functional outcome at 90 days (P<0.0001) after adjusting for potential confounders. Patients with high and high-to-moderate SBP trajectories had significantly greater odds of an unfavorable outcome (adjusted odds ratio, 3.5 [95% CI, 1.8-6.7], P=0.0003 and adjusted odds ratio, 2.2 [95% CI, 1.5-3.2], P<0.0001, respectively). Subjects in the high-to-moderate group had an increased risk of symptomatic intracranial hemorrhage (adjusted odds ratio, 1.82 [95% CI, 1-3.2]; P=0.04). No significant association was found between trajectory group and hemorrhagic transformation. CONCLUSIONS: Patients with acute ischemic stroke demonstrate distinct SBP trajectories during the first 72 hours after EVT that have differing associations with functional outcome. These findings may help identify potential candidates for future blood pressure modulation trials.

Anticoagulation Timing in Cardioembolic Stroke and Recurrent Event Risk.

OBJECTIVE: Guidelines recommend initiating anticoagulation within 4 to 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/transient ischemic attack/systemic embolism, symptomatic intracerebral hemorrhage (sICH), and major extracranial hemorrhage (ECH) within 90 days. RESULTS: Among 2,084 patients, 1,289 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 3 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 and 14 days did not have a lower rate of sICH (vs 0-3 days; odds ratio [OR] = 1.49, 95% confidence interval [CI] = 0.50-4.43), nor 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. ANN NEUROL 2020;88:807-816.

Ischaemic stroke on anticoagulation therapy and early recurrence in acute cardioembolic stroke: the IAC study.

BACKGROUND AND PURPOSE: A subset of ischaemic stroke patients with atrial fibrillation (AF) have ischaemic stroke despite anticoagulation. We sought to determine the association between prestroke anticoagulant therapy and recurrent ischaemic events and symptomatic intracranial haemorrhage (sICH). METHODS: We included consecutive patients with acute ischaemic stroke and AF from the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study from eight comprehensive stroke centres in the USA. We compared recurrent ischaemic events and delayed sICH risk using adjusted Cox regression analyses between patients who were prescribed anticoagulation (ACp) versus patients who were naïve to anticoagulation therapy prior to the ischaemic stroke (anticoagulation naïve). RESULTS: Among 2084 patients in IAC, 1518 had prior anticoagulation status recorded and were followed for 90 days. In adjusted Cox hazard models, ACp was associated with some evidence of a higher risk higher risk of 90-day recurrent ischaemic events only in the fully adjusted model (adjusted HR 1.50, 95% CI 0.99 to 2.28, p=0.058) but not increased risk of 90-day sICH (adjusted HR 1.08, 95% CI 0.46 to 2.51, p=0.862). In addition, switching anticoagulation class was not associated with reduced risk of recurrent ischaemic events (adjusted HR 0.41, 95% CI 0.12 to 1.33, p=0.136) nor sICH (adjusted HR 1.47, 95% CI 0.29 to 7.50, p=0.641). CONCLUSION: AF patients with ischaemic stroke despite anticoagulation may have higher recurrent ischaemic event risk compared with anticoagulation-naïve patients. This suggests differing underlying pathomechanisms requiring different stroke prevention measures and identifying these mechanisms may improve secondary 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, treatment with low molecular weight heparin 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. METHODS: We included consecutive patients with acute ischemic stroke and atrial fibrillation from the IAC (Initiation of Anticoagulation after Cardioembolic) stroke study pooling data from stroke registries of 8 comprehensive stroke centers across the United States. We compared recurrent ischemic events and delayed symptomatic intracranial hemorrhage between each of the following groups in separate Cox-regression analyses: (1) DOAC versus warfarin and (2) bridging with heparin/low molecular weight heparin versus no bridging, adjusting for pertinent confounders to test these associations. RESULTS: We identified 1289 patients who met the bridging versus no bridging analysis inclusion criteria and 1251 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 delayed symptomatic intracranial hemorrhage (hazard ratio, 2.74 [95% CI, 1.01-7.42]) but a similar rate of recurrent ischemic events (hazard ratio, 1.23 [95% CI, 0.63-2.40]). Furthermore, DOAC (versus warfarin) treatment was associated with a lower risk of recurrent ischemic events (hazard ratio, 0.51 [95% CI, 0.29-0.87]) but not delayed symptomatic intracranial hemorrhage (hazard ratio, 0.57 [95% CI, 0.22-1.48]). CONCLUSIONS: Our study suggests that patients with ischemic stroke and atrial fibrillation 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.

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

INTRODUCTION: Predictors of long-term ischaemic and haemorrhagic complications in atrial fibrillation (AF) have been studied, but there are limited data on predictors of early ischaemic and haemorrhagic complications after AF-associated ischaemic stroke. We sought to determine these predictors. METHODS: The Initiation of Anticoagulation after Cardioembolic stroke study is a multicentre retrospective study across that pooled data from consecutive patients with ischaemic stroke in the setting of AF from stroke registries across eight comprehensive stroke centres in the USA. The coprimary outcomes were recurrent ischaemic event (stroke/TIA/systemic arterial embolism) and delayed symptomatic intracranial haemorrhage (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 ischaemic events (stroke/TIA/systemic embolism) and d-sICH. RESULTS: Out of 2084 patients, 1520 patients qualified; 104 patients (6.8%) had recurrent ischaemic 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 ischaemic events were prior stroke or transient ischemic attack (TIA) (HR 1.42, 95% CI 0.96 to 2.10) and ipsilateral arterial stenosis with 50%-99% narrowing (HR 1.54, 95% CI 0.98 to 2.43). Those associated with sICH were male sex (HR 2.68, 95% CI 1.06 to 6.83), history of hyperlipidaemia (HR 2.91, 95% CI 1.08 to 7.84) and early haemorrhagic transformation (HR 5.35, 95% CI 2.22 to 12.92). CONCLUSION: In patients with ischaemic stroke and AF, predictors of d-sICH are different than those of recurrent ischaemic events; therefore, recognising these predictors may help inform early stroke versus d-sICH prevention strategies.

Factors associated with therapeutic anticoagulation status in patients with ischemic stroke and atrial fibrillation.

BACKGROUND AND PURPOSE: Understanding factors associated with ischemic stroke despite therapeutic anticoagulation is an important goal to improve stroke prevention strategies in patients with atrial fibrillation (AF). We aim to determine factors associated with therapeutic or supratherapeutic anticoagulation status at the time of ischemic stroke in patients with AF. METHODS: The Initiation of Anticoagulation after Cardioembolic stroke (IAC) study is a multicenter study pooling data from stroke registries of eight comprehensive stroke centers across the United States. Consecutive patients hospitalized with acute ischemic stroke in the setting of AF were included in the IAC cohort. For this study, we only included patients who reported taking warfarin at the time of the ischemic stroke. Patients not on anticoagulation and patients who reported use of a direct oral anticoagulant were excluded. Analyses were stratified based on therapeutic (INR ≥2) versus subtherapeutic (INR <2) anticoagulation status. We used binary logistic regression models to determine factors independently associated with anticoagulation status after adjustment for pertinent confounders. In particular, we sought to determine whether atherosclerosis with 50% or more luminal narrowing in an artery supplying the infarct (a marker for a competing atherosclerotic mechanism) and small stroke size (≤ 10 mL; implying a competing small vessel disease mechanism) related to anticoagulant status. RESULTS: Of the 2084 patients enrolled in the IAC study, 382 patients met the inclusion criteria. The mean age was 77.4 ± 10.9 years and 52.4% (200/382) were women. A total of 222 (58.1%) subjects presented with subtherapeutic INR. In adjusted models, small stroke size (OR 1.74 95% CI 1.10-2.76, p = 0.019) and atherosclerosis with 50% or more narrowing in an artery supplying the infarct (OR 1.96 95% CI 1.06-3.63, p = 0.031) were independently associated with INR ≥2 at the time of their index stroke. CONCLUSION: Small stroke size (≤ 10 ml) and ipsilateral atherosclerosis with 50% or more narrowing may indicate a competing stroke mechanism. There may be important opportunities to improve stroke prevention strategies for patients with AF by targeting additional ischemic stroke mechanisms to improve patient outcomes.

Temporal profiles of systolic blood pressure variability and neurologic outcomes after endovascular thrombectomy.

Introduction: Observational studies have found an increased risk of hemorrhagic transformation and worse functional outcomes in patients with higher systolic blood pressure variability (BPV). However, the time-varying behavior of BPV after endovascular thrombectomy (EVT) and its effects on functional outcome have not been well characterized. Patients and methods: We analyzed data from an international cohort of patients with large-vessel occlusion stroke who underwent EVT at 11 centers across North America, Europe, and Asia. Repeated time-stamped blood pressure data were recorded for the first 72 h after thrombectomy. Parameters of BPV were calculated in 12-h epochs using five established methodologies. Systolic BPV trajectories were generated using group-based trajectory modeling, which separates heterogeneous longitudinal data into groups with similar patterns. Results: Of the 2041 patients (age 69 ± 14, 51.4% male, NIHSS 15 ± 7, mean number of BP measurements 50 ± 28) included in our analysis, 1293 (63.4%) had a poor 90-day outcome (mRS ⩾ 3) or a poor discharge outcome (mRS ⩾ 3). We identified three distinct SBP trajectories: low (25%), moderate (64%), and high (11%). Compared to patients with low BPV, those in the highest trajectory group had a significantly greater risk of a poor functional outcome after adjusting for relevant confounders (OR 2.2; 95% CI 1.2-3.9; p = 0.008). In addition, patients with poor outcomes had significantly higher systolic BPV during the epochs that define the first 24 h after EVT (p < 0.001). Discussion and conclusions: Acute ischemic stroke patients demonstrate three unique systolic BPV trajectories that differ in their association with functional outcome. Further research is needed to rapidly identify individuals with high-risk BPV trajectories and to develop treatment strategies for targeting high BPV.

Effect of Alteplase Use on Outcomes in Patients With Atrial Fibrillation: Analysis of the Initiation of Anticoagulation After Cardioembolic Stroke Study.

Background Intravenous alteplase improves outcome after acute ischemic stroke without a benefit in 90-day mortality. There are limited data on whether alteplase is associated with reduced mortality in patients with atrial fibrillation (AF)-related ischemic stroke whose mortality rate is relatively high. We sought to determine the association of alteplase with hemorrhagic transformation and mortality in patients with AF. Methods and Results We retrospectively analyzed consecutive patients with acute ischemic stroke between 2015 and 2018 diagnosed with AF included in the IAC (Initiation of Anticoagulation After Cardioembolic Stroke) study, which pooled data from stroke registries at 8 comprehensive stroke centers across the United States. For our primary analysis, we included patients who did not undergo mechanical thrombectomy (MT), and secondary analyses included patients who underwent MT. We used binary logistic regression to determine whether alteplase use was associated with risk of hemorrhagic transformation and 90-day mortality. There were 1889 patients (90.6%) who had 90-day follow-up data available for analyses and were included; 1367 patients (72.4%) did not receive MT, and 522 patients (27.6%) received MT. In our primary analyses we found that alteplase use was independently associated with an increased risk for hemorrhagic transformation (odds ratio [OR], 2.23; 95% CI, 1.57-3.17) but reduced risk of 90-day mortality (OR, 0.58; 95% CI, 0.39-0.87). Among patients undergoing MT, alteplase use was not associated with a significant reduction in 90-day mortality (OR, 0.68; 95% CI, 0.45-1.04). Conclusions Alteplase reduced 90-day mortality of patients with acute ischemic stroke with AF not undergoing MT. Further study is required to assess the efficacy of alteplase in patients with AF undergoing MT.