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Introduction: Extracranial internal carotid artery dissection (eICAD) is a leading cause of stroke in younger patients. In this Cochrane Review update we compared benefits and harms of eICAD-patients treated with either antiplatelets or anticoagulants., Patients and Methods: Eligible studies were identified through Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE, and EMBASE and personal search until December 2023. We included randomized-controlled trials (RCTs) and non-randomized studies comparing anticoagulants with antiplatelets in eICAD-patients. Co-primary outcomes were (i) death (all causes) and (ii) death or disability. Secondary outcomes were ischemic stroke, symptomatic intracranial hemorrhage, and major extracranial hemorrhage. Odds ratios (OR) with 95% CIs were calculated for (i) all studies and (ii) separately for RCTs and non-randomized studies., Results: We meta-analyzed a total of 42 studies (2624 patients) including 2 RCTs (213 patients) for the primary outcome of death and 31 studies (1953 patients) including 1 RCT (115 patients) for the primary outcome of death or disability. Antiplatelet-treated patients had higher odds for death (OR all-studies 2.70, 95% CI 1.27-5.72; OR RTCs 6.80, 95% CI 0.14-345; OR non-randomized studies 2.60, 95% CI 1.20-5.60) and death or disability (OR all-studies 2.1, 95% CI 1.58-2.66; OR RTCs 2.2, 95% CI 0.29-16.05; OR non-randomized studies 2.1, 95% CI 1.58-2.66) than anticoagulated patients. Antiplatelet-treated patients had also higher odds for ischemic stroke, though this reached statistical significance only in the subgroup of RCTs (OR RTC 4.60, 95% CI 1.36-15.51). In turn, antiplatelet-treated patients had less symptomatic intracranial hemorrhage (OR all-studies 0.25, 95% CI 0.07-0.86) and a tendency toward less major extracranial hemorrhage (OR all-studies 0.17, 95% CI 0.03-1.03)., Discussion and Conclusion: The evidence considering antiplatelets as standard of care in eICAD is weak. Individualized treatment decisions balancing risks versus harms seem recommendable., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: STE reports grants from Swiss National Science Foundation, Swiss Heart Foundation, FAG Basel, University of Basel, the Neurology Department of the University Hospital Basel, and the Science Fund Rehabilitation of the University Department of Geriatric Medicine Felix Platter Basel. He had travel grants, speaker honoraria, or scientific advisory board compensations from Bayer and Boehringer Ingelheim, and his institutions had received an educational grant from Pfizer and research support from Daiichi-Sankyo (outside this research).PL reports grants from Bayer, Swiss National Science Foundation, and ProPatient Foundation of the University Hospital Basel; the Neurology Department of the University Hospital Basel; compensation for research activities from Acticor, outside of the submitted work.All other authors report no disclosures.

Background: Data on the safety and effectiveness of once-daily (QD) versus twice-daily (BID) direct oral anticoagulants (DOAC) in comparison to vitamin K antagonists (VKA) and to one another in patients with atrial fibrillation (AF) and recent stroke are scarce., Patients and Methods: Based on prospectively obtained data from the observational registry Novel-Oral-Anticoagulants-in-Ischemic-Stroke-Patients(NOACISP)-LONGTERM (NCT03826927) from Basel, Switzerland, we compared the occurrence of the primary outcome - the composite of recurrent ischemic stroke, major bleeding, and all-cause death - among consecutive AF patients treated with either VKA, QD DOAC, or BID DOAC following a recent stroke using Cox proportional hazards regression including adjustment for potential confounders., Results: We analyzed 956 patients (median age 80 years, 46% female), of whom 128 received VKA (13.4%), 264 QD DOAC (27.6%), and 564 BID DOAC (59%). Over a total follow-up of 1596 patient-years, both QD DOAC and BID DOAC showed a lower hazard for the composite outcome compared to VKA (adjusted HR [95% CI] 0.69 [0.48, 1.01] and 0.66 [0.47, 0.91], respectively). Upon direct comparison, the hazard for the composite outcome did not differ between patients treated with QD versus BID DOAC (adjusted HR [95% CI] 0.94 [0.70, 1.26]). Secondary analyses focusing on the individual components of the composite outcome revealed no clear differences in the risk-benefit profile of QD versus BID DOAC., Discussion and Conclusion: The overall benefit of DOAC over VKA seems to apply to both QD and BID DOAC in AF patients with a recent stroke, without clear evidence that one DOAC dosing regimen is more advantageous than the other., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AP: research support from the Swiss Academy of Medical Sciences/Bangerter-Rhyner Foundation and the Swiss Heart Foundation; CT: travel honoraria from Bayer; research support from the Swiss Heart Foundation, Freiwillige Akademische Gesellschaft Basel, Bangerter-Rhyner Foundation, University of Basel, Novartis Foundation for Medical and Biological Research; ST: travel grants from BMS/Pfizer; DJS: research support from the Science Funds and Stroke Funds University Hospital Basel, Swiss National Science Foundation, Swiss Society of Neurology, Bangerter-Rhyner Foundation, Daiichi-Sankyo; Thrombosis research prize from Bayer Foundation; compensation for educational efforts from Stago; advisory board fees from Portola/Alexion, Bayer, Pfizer; NP: research support from the Swiss National Science Foundation, Swiss Heart Foundation; advisory boards for AstraZeneca and Daiichi-Sankyo; speaker honoraria from Vifor and OMPharma Suisse; GMDM: support from the Swiss National Science Foundation; Spezialprogramm Nachwuchsförderung Klinische Forschung, University of Basel; Science Funds (Wissenschaftspool) University Hospital Basel; Swiss Heart Foundation; ProPatient Foundation Basel; Bangerter-Rhyner-Stiftung; Swisslife Jubiläumsstiftung for Medical Research; Swiss Neurological Society; Fondazione Dr Ettore Balli; De Quervain research grant; Thermo Fisher GmbH; travel honoraria by Bayer and BMS/Pfizer; speaker honoraria by Bayer and Medtronic; consultant honoraria by Bayer and Novartis; member of the Steering Committee of PACIFIC Stroke; Industry payments are made to the research fund of the University Hospital Basel; LHB: research support from the Swiss Heart Foundation, Swiss National Science Foundation, Stiftung zur Förderung der gastroenterologischen und allgemeinen klinischen Forschung sowie der medizinischen Bildauswertung; unrestricted research grant from AstraZeneca, personal fees from Amgen, Claret Medical, InnovHeart; HG: research support from the Swiss National Science Foundation; advisory board honoraria from Daiichi-Sankyo; funding for travel from BMS/Pfizer and AbbVie; STE: research support from the Swiss National Science Foundation, Swiss Heart Foundation, Freiwillige Akademische Gesellschaft Basel, Science Fund Rehabilitation, Felix Platter Basel, the Stroke Fund and Scientific Fund of the University Hospital Basel, Pfizer, Daiichi-Sankyo; compensation from Stago for educational material; travel or speaker honoraria from Bayer, Boehringer-Ingelheim, BMS, Daiichi-Sankyo; advisory boards for Bayer, Boehringer-Ingelheim, BMS; PAL: research support from the Swiss National Science Foundation, Swiss Heart Foundation, Research Funds Neurology University Hospital Basel; advisory board compensation from Boehringer-Ingelheim, Bayer, Recordati SA, Daiichi-Sankyo; travel support from Pfizer. The remaining authors declare no relevant conflicts., (© European Stroke Organisation 2022.)

Objective: To investigate the safety and effectiveness of direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) after recent stroke in patients with atrial fibrillation (AF) aged ≥85 years., Methods: Individual patient data analysis from seven prospective stroke cohorts. We compared DOAC versus VKA treatment among patients with AF and recent stroke (<3 months) aged ≥85 versus <85 years. Primary outcome was the composite of recurrent stroke, intracranial hemorrhage (ICH) and all-cause death. We used simple, adjusted, and weighted Cox regression to account for confounders. We calculated the net benefit of DOAC versus VKA by balancing stroke reduction against the weighted ICH risk., Results: In total, 5,984 of 6,267 (95.5%) patients were eligible for analysis. Of those, 1,380 (23%) were aged ≥85 years and 3,688 (62%) received a DOAC. During 6,874 patient-years follow-up, the impact of anticoagulant type (DOAC versus VKA) on the hazard for the composite outcome did not differ between patients aged ≥85 (HR ≥85y  = 0.65, 95%-CI [0.52, 0.81]) and < 85 years (HR <85y  = 0.79, 95%-CI [0.66, 0.95]) in simple (p interaction  = 0.129), adjusted (p interaction  = 0.094) or weighted (p interaction  = 0.512) models. Analyses on recurrent stroke, ICH and death separately were consistent with the primary analysis, as were sensitivity analyses using age dichotomized at 90 years and as a continuous variable. DOAC had a similar net clinical benefit in patients aged ≥85 (+1.73 to +2.66) and < 85 years (+1.90 to +3.36 events/100 patient-years for ICH-weights 1.5 to 3.1)., Interpretation: The favorable profile of DOAC over VKA in patients with AF and recent stroke was maintained in the oldest old. ANN NEUROL 2022;91:78-88., (© 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)