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  • American Medical Association (AMA)  (5)
  • 1
    In: JAMA, American Medical Association (AMA), Vol. 331, No. 9 ( 2024-03-05), p. 750-
    Abstract: Whether endovascular thrombectomy (EVT) efficacy for patients with acute ischemic stroke and large cores varies depending on the extent of ischemic injury is uncertain. Objective To describe the relationship between imaging estimates of irreversibly injured brain (core) and at-risk regions (mismatch) and clinical outcomes and EVT treatment effect. Design, Setting, and Participants An exploratory analysis of the SELECT2 trial, which randomized 352 adults (18-85 years) with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) and large ischemic core to EVT vs medical management (MM), across 31 global centers between October 2019 and September 2022. Intervention EVT vs MM. Main Outcomes and Measures Primary outcome was functional outcome—90-day mRS score (0, no symptoms, to 6, death) assessed by adjusted generalized OR (aGenOR; values & amp;gt;1 represent more favorable outcomes). Benefit of EVT vs MM was assessed across levels of ischemic injury defined by noncontrast CT using ASPECTS score and by the volume of brain with severely reduced blood flow on CT perfusion or restricted diffusion on MRI. Results Among 352 patients randomized, 336 were analyzed (median age, 67 years; 139 [41.4%] female); of these, 168 (50%) were randomized to EVT, and 2 additional crossover MM patients received EVT. In an ordinal analysis of mRS at 90 days, EVT improved functional outcomes compared with MM within ASPECTS categories of 3 (aGenOR, 1.71 [95% CI, 1.04-2.81] ), 4 (aGenOR, 2.01 [95% CI, 1.19-3.40]), and 5 (aGenOR, 1.85 [95% CI, 1.22-2.79] ). Across strata for CT perfusion/MRI ischemic core volumes, aGenOR for EVT vs MM was 1.63 (95% CI, 1.23-2.16) for volumes ≥70 mL, 1.41 (95% CI, 0.99-2.02) for ≥100 mL, and 1.47 (95% CI, 0.84-2.56) for ≥150 mL. In the EVT group, outcomes worsened as ASPECTS decreased (aGenOR, 0.91 [95% CI, 0.82-1.00] per 1-point decrease) and as CT perfusion/MRI ischemic core volume increased (aGenOR, 0.92 [95% CI, 0.89-0.95] per 10-mL increase). No heterogeneity of EVT treatment effect was observed with or without mismatch, although few patients without mismatch were enrolled. Conclusion and Relevance In this exploratory analysis of a randomized clinical trial of patients with extensive ischemic stroke, EVT improved clinical outcomes across a wide spectrum of infarct volumes, although enrollment of patients with minimal penumbra volume was low. In EVT-treated patients, clinical outcomes worsened as presenting ischemic injury estimates increased. Trial Registration ClinicalTrials.gov Identifier: NCT03876457
    Type of Medium: Online Resource
    ISSN: 0098-7484
    RVK:
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2024
    detail.hit.zdb_id: 2958-0
    SSG: 5,21
    Location Call Number Limitation Availability
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  • 2
    In: JAMA, American Medical Association (AMA), Vol. 331, No. 7 ( 2024-02-20), p. 573-
    Abstract: Atrial cardiopathy is associated with stroke in the absence of clinically apparent atrial fibrillation. It is unknown whether anticoagulation, which has proven benefit in atrial fibrillation, prevents stroke in patients with atrial cardiopathy and no atrial fibrillation. Objective To compare anticoagulation vs antiplatelet therapy for secondary stroke prevention in patients with cryptogenic stroke and evidence of atrial cardiopathy. Design, Setting, and Participants Multicenter, double-blind, phase 3 randomized clinical trial of 1015 participants with cryptogenic stroke and evidence of atrial cardiopathy, defined as P-wave terminal force greater than 5000 μV × ms in electrocardiogram lead V 1 , serum N-terminal pro-B-type natriuretic peptide level greater than 250 pg/mL, or left atrial diameter index of 3 cm/m 2 or greater on echocardiogram. Participants had no evidence of atrial fibrillation at the time of randomization. Enrollment and follow-up occurred from February 1, 2018, through February 28, 2023, at 185 sites in the National Institutes of Health StrokeNet and the Canadian Stroke Consortium. Interventions Apixaban, 5 mg or 2.5 mg, twice daily (n = 507) vs aspirin, 81 mg, once daily (n = 508). Main Outcomes and Measures The primary efficacy outcome in a time-to-event analysis was recurrent stroke. All participants, including those diagnosed with atrial fibrillation after randomization, were analyzed according to the groups to which they were randomized. The primary safety outcomes were symptomatic intracranial hemorrhage and other major hemorrhage. Results With 1015 of the target 1100 participants enrolled and mean follow-up of 1.8 years, the trial was stopped for futility after a planned interim analysis. The mean (SD) age of participants was 68.0 (11.0) years, 54.3% were female, and 87.5% completed the full duration of follow-up. Recurrent stroke occurred in 40 patients in the apixaban group (annualized rate, 4.4%) and 40 patients in the aspirin group (annualized rate, 4.4%) (hazard ratio, 1.00 [95% CI, 0.64-1.55]). Symptomatic intracranial hemorrhage occurred in 0 patients taking apixaban and 7 patients taking aspirin (annualized rate, 1.1%). Other major hemorrhages occurred in 5 patients taking apixaban (annualized rate, 0.7%) and 5 patients taking aspirin (annualized rate, 0.8%) (hazard ratio, 1.02 [95% CI, 0.29-3.52] ). Conclusions and Relevance In patients with cryptogenic stroke and evidence of atrial cardiopathy without atrial fibrillation, apixaban did not significantly reduce recurrent stroke risk compared with aspirin. Trial Registration ClinicalTrials.gov Identifier: NCT03192215
    Type of Medium: Online Resource
    ISSN: 0098-7484
    RVK:
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2024
    detail.hit.zdb_id: 2958-0
    SSG: 5,21
    Location Call Number Limitation Availability
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  • 3
    In: JAMA Neurology, American Medical Association (AMA), Vol. 81, No. 4 ( 2024-04-01), p. 327-
    Abstract: Patients with large ischemic core stroke have poor clinical outcomes and are frequently not considered for interfacility transfer for endovascular thrombectomy (EVT). Objective To assess EVT treatment effects in transferred vs directly presenting patients and to evaluate the association between transfer times and neuroimaging changes with EVT clinical outcomes. Design, Setting, and Participants This prespecified secondary analysis of the SELECT2 trial, which evaluated EVT vs medical management (MM) in patients with large ischemic stroke, evaluated adults aged 18 to 85 years with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) as well as an Alberta Stroke Program Early CT Score (ASPECTS) of 3 to 5, core of 50 mL or greater on imaging, or both. Patients were enrolled between October 2019 and September 2022 from 31 EVT-capable centers in the US, Canada, Europe, Australia, and New Zealand. Data were analyzed from August 2023 to January 2024. Interventions EVT vs MM. Main Outcomes and Measures Functional outcome, defined as modified Rankin Scale (mRS) score at 90 days with blinded adjudication. Results A total of 958 patients were screened and 606 patients were excluded. Of 352 enrolled patients, 145 (41.2%) were female, and the median (IQR) age was 66.5 (58-75) years. A total of 211 patients (59.9%) were transfers, while 141 (40.1%) presented directly. The median (IQR) transfer time was 178 (136-230) minutes. The median (IQR) ASPECTS decreased from the referring hospital (5 [4-7]) to an EVT-capable center (4 [3-5] ). Thrombectomy treatment effect was observed in both directly presenting patients (adjusted generalized odds ratio [OR], 2.01; 95% CI, 1.42-2.86) and transferred patients (adjusted generalized OR, 1.50; 95% CI, 1.11-2.03) without heterogeneity ( P for interaction = .14). Treatment effect point estimates favored EVT among 82 transferred patients with a referral hospital ASPECTS of 5 or less (44 received EVT; adjusted generalized OR, 1.52; 95% CI, 0.89-2.58). ASPECTS loss was associated with numerically worse EVT outcomes (adjusted generalized OR per 1-ASPECTS point loss, 0.89; 95% CI, 0.77-1.02). EVT treatment effect estimates were lower in patients with transfer times of 3 hours or more (adjusted generalized OR, 1.15; 95% CI, 0.73-1.80). Conclusions and Relevance Both directly presenting and transferred patients with large ischemic stroke in the SELECT2 trial benefited from EVT, including those with low ASPECTS at referring hospitals. However, the association of EVT with better functional outcomes was numerically better in patients presenting directly to EVT-capable centers. Prolonged transfer times and evolution of ischemic change were associated with worse EVT outcomes. These findings emphasize the need for rapid identification of patients suitable for transfer and expedited transport. Trial Registration ClinicalTrials.gov Identifier: NCT03876457
    Type of Medium: Online Resource
    ISSN: 2168-6149
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2024
    detail.hit.zdb_id: 2702023-X
    Location Call Number Limitation Availability
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  • 4
    In: JAMA Neurology, American Medical Association (AMA), Vol. 74, No. 3 ( 2017-03-01), p. 301-
    Type of Medium: Online Resource
    ISSN: 2168-6149
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2017
    detail.hit.zdb_id: 2702023-X
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  • 5
    In: JAMA Neurology, American Medical Association (AMA), Vol. 80, No. 8 ( 2023-08-01), p. 833-
    Abstract: After aneurysmal subarachnoid hemorrhage, the use of lumbar drains has been suggested to decrease the incidence of delayed cerebral ischemia and improve long-term outcome. Objective To determine the effectiveness of early lumbar cerebrospinal fluid drainage added to standard of care in patients after aneurysmal subarachnoid hemorrhage. Design, Setting, and Participants The EARLYDRAIN trial was a pragmatic, multicenter, parallel-group, open-label randomized clinical trial with blinded end point evaluation conducted at 19 centers in Germany, Switzerland, and Canada. The first patient entered January 31, 2011, and the last on January 24, 2016, after 307 randomizations. Follow-up was completed July 2016. Query and retrieval of data on missing items in the case report forms was completed in September 2020. A total of 20 randomizations were invalid, the main reason being lack of informed consent. No participants meeting all inclusion and exclusion criteria were excluded from the intention-to-treat analysis. Exclusion of patients was only performed in per-protocol sensitivity analysis. A total of 287 adult patients with acute aneurysmal subarachnoid hemorrhage of all clinical grades were analyzable. Aneurysm treatment with clipping or coiling was performed within 48 hours. Intervention A total of 144 patients were randomized to receive an additional lumbar drain after aneurysm treatment and 143 patients to standard of care only. Early lumbar drainage with 5 mL per hour was started within 72 hours of the subarachnoid hemorrhage. Main Outcomes and Measures Primary outcome was the rate of unfavorable outcome, defined as modified Rankin Scale score of 3 to 6 (range, 0 to 6), obtained by masked assessors 6 months after hemorrhage. Results Of 287 included patients, 197 (68.6%) were female, and the median (IQR) age was 55 (48-63) years. Lumbar drainage started at a median (IQR) of day 2 (1-2) after aneurysmal subarachnoid hemorrhage. At 6 months, 47 patients (32.6%) in the lumbar drain group and 64 patients (44.8%) in the standard of care group had an unfavorable neurological outcome (risk ratio, 0.73; 95% CI, 0.52 to 0.98; absolute risk difference, −0.12; 95% CI, −0.23 to −0.01; P  = .04). Patients treated with a lumbar drain had fewer secondary infarctions at discharge (41 patients [28.5%] vs 57 patients [39.9%] ; risk ratio, 0.71; 95% CI, 0.49 to 0.99; absolute risk difference, −0.11; 95% CI, −0.22 to 0; P  = .04). Conclusion and Relevance In this trial, prophylactic lumbar drainage after aneurysmal subarachnoid hemorrhage lessened the burden of secondary infarction and decreased the rate of unfavorable outcome at 6 months. These findings support the use of lumbar drains after aneurysmal subarachnoid hemorrhage. Trial Registration ClinicalTrials.gov Identifier: NCT01258257
    Type of Medium: Online Resource
    ISSN: 2168-6149
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
    detail.hit.zdb_id: 2702023-X
    Location Call Number Limitation Availability
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