The impact of competing stroke etiologies in patients with atrial fibrillation.

BACKGROUND Data on the impact of competing stroke etiologies in stroke patients with atrial fibrillation (AF) are scarce. METHODS We used prospectively obtained data from an observational registry (Novel-Oral-Anticoagulants-in-Ischemic-Stroke-Patients-(NOACISP)-LONGTERM) of consecutive AF-stroke patients treated with oral anticoagulants. We compared the frequency of (i) the composite outcome of recurrent ischemic stroke (IS), intracerebral hemorrhage (ICH) or all-cause death as well as (ii) recurrent IS alone among AF-stroke patients with versus without competing stroke etiologies according to the TOAST classification. We performed cox proportional hazards regression modeling adjusted for potential confounders. Furthermore, the etiology of recurrent IS was assessed. RESULTS Among 907 patients (median age 81, 45.6% female), 184 patients (20.3%) had competing etiologies, while 723 (79.7%) had cardioembolism as the only plausible etiology. During 1587 patient-years of follow-up, patients with additional large-artery atherosclerosis had higher rates of the composite outcome (adjusted HR [95% CI] 1.64 [1.11, 2.40], p = 0.017) and recurrent IS (aHR 2.96 [1.65, 5.35 ], p < 0.001), compared to patients with cardioembolism as the only plausible etiology. Overall 71 patients had recurrent IS (7.8%) of whom 26.7% had a different etiology than the index IS with large-artery-atherosclerosis (19.7%) being the most common non-cardioembolic cause. CONCLUSION In stroke patients with AF, causes other than cardioembolism as competing etiologies were common in index or recurrent IS. Concomitant presence of large-artery-atherosclerosis seems to indicate an increased risk for recurrences suggesting that stroke preventive means might be more effective if they also address competing stroke etiologies in AF-stroke patients. CLINICAL TRIAL REGISTRATION NCT03826927

Impact of Modified Frozen Elephant Trunk Procedure on Downstream Aorta Remodeling in Acute Aortic Dissection: CT Scan Follow-Up

The aim was to evaluate the impact of a modified frozen elephant trunk procedure (mFET) on remodeling of the downstream aorta following acute aortic dissections.; Over a period of 8 years, 205 patients (mean age 62.6 ± 12.6 years) underwent a mFET (n = 69, 33.7%) or isolated ascending aorta replacement (n = 136, 66.3%) (iAoA). Aortic diameter was assessed at the aortic arch (AoA), at the mid of the thoracic aorta (mThA), at the thoracoabdominal transition (ThAbd) and at the celiac trunk level (AbdA).; Mean follow-up was 3.3 ± 2.6 years. In-hospital mortality was 14% (n = 28), 7% in mFET and 17% in the iAoA group (p = 0.08). At the end of the follow-up, overall survival was 84% (95% CI 70-92%) and 75% (65-82%) and freedom from aorta-related reoperation was 100% and 95% (88-98%) for mFET and iAoA, respectively. At iAoA, the average difference in diameter change per year between mFET and iAoA was for total lumen 0 mm (- 0.95 to 0.94 mm, p = 0.99), and for true lumen, it was 1.23 mm (- 0.09 to 2.55 mm) per year, p = 0.067. False lumen demonstrated a decrease in diameter in mFET as compared to iAoA by - 1.43 mm (- 2.75 to - 0.11 mm), p = 0.034. In mFET, at the aortic arch level the total lumen diameter decreased from 30.7 ± 4.8 mm to 30.1 ± 2.5 mm (Δr + 2.90 ± 3.64 mm) and in iAoA it increased from 31.8 ± 4.9 to 34.6 ± 5.9 mm (Δr + 2.88 ± 4.18 mm).; The mFET procedure provides satisfactory clinical outcome at short term and mid-term and has a positive impact on aorta remodeling, especially at the level of the aortic arch

Toward Individual Treatment in Cervical Artery Dissection: Subgroup Analysis of the TREAT-CAD Randomized Trial.

OBJECTIVE Uncertainty remains regarding antithrombotic treatment in cervical artery dissection. This analysis aimed to explore whether certain patient profiles influence the effects of different types of antithrombotic treatment. METHODS This was a post hoc exploratory analysis based on the per-protocol dataset from TREAT-CAD (NCT02046460), a randomized controlled trial comparing aspirin to anticoagulation in patients with cervical artery dissection. We explored the potential effects of distinct patient profiles on outcomes in participants treated with either aspirin or anticoagulation. Profiles included (1) presenting with ischemia (no/yes), (2) occlusion of the dissected artery (no/yes), (3) early versus delayed treatment start (median), and (4) intracranial extension of the dissection (no/yes). Outcomes included clinical (stroke, major hemorrhage, death) and magnetic resonance imaging outcomes (new ischemic or hemorrhagic brain lesions) and were assessed for each subgroup in separate logistic models without adjustment for multiple testing. RESULTS All 173 (100%) per-protocol participants were eligible for the analyses. Participants without occlusion had decreased odds of events when treated with anticoagulation (odds ratio [OR] = 0.28, 95% confidence interval [CI] = 0.07-0.86). This effect was more pronounced in participants presenting with cerebral ischemia (n = 118; OR = 0.16, 95% CI = 0.04-0.55). In the latter, those with early treatment (OR = 0.26, 95% CI = 0.07-0.85) or without intracranial extension of the dissection (OR = 0.34, 95% CI = 0.11-0.97) had decreased odds of events when treated with anticoagulation. INTERPRETATION Anticoagulation might be preferable in patients with cervical artery dissection presenting with ischemia and no occlusion or no intracranial extension of the dissection. These findings need confirmation. ANN NEUROL 2024

Antithrombotic treatment for cervical artery dissection: An individual patient data meta-analysis of the CADISS and TREAT-CAD randomized trials

Importance: Cervical artery dissection is the most common cause of stroke in the young. To date, there is no conclusive evidence on which antithrombotic therapy should be used to treat patients. Objective: An individual patient data meta-analysis of previous randomized controlled trials comparing anticoagulants and antiplatelets in prevention of stroke after cervical artery dissection. Data Sources: We searched Pubmed.gov, Cochrane, Embase, and ClinicalTrials.gov from inception to August 1, 2023. Study Selection: Randomized controlled trials that investigated the effectiveness and safety of antithrombotic treatment (antiplatelets versus anticoagulation) in cervical artery dissection patients. The primary endpoint was required to include (i) any stroke, (ii) death, or (iii) major bleeding (extra- or intracranial) at 90 days follow-up. Data Extraction/Synthesis: Two independent investigators performed a systematic review according to the PRIMSA guidelines and inconsistencies were resolved by a principal investigator. Main Outcomes/Measures: The primary outcome was a composite of (i) ischemic stroke, (ii) death, or (iii) major bleeding (extra- or intracranial) at 90 days follow-up. The components of the composite outcome were also secondary outcomes. Subgroup analyses based on baseline characteristics with a putative impact on the outcome were performed. We performed logistic regression using the maximum penalized likelihood method including interaction in the subgroup analyses. Results: We identified two randomized controlled trials, CADISS and TREAT-CAD, of which all participants were eligible. 444 patients were included in the intention-to-treat (ITT) population and 370 patients in the per-protocol (PP) population. Baseline characteristics were balanced. There was a non-significant tendency for there to be fewer primary endpoints in those randomized to anticoagulation vs aspirin (3/218 [1.4%] vs 10/226 [4.4%], OR=0.33 [95% CI 0.08-1.05], p=0.061). In comparison with aspirin, anticoagulation was associated with fewer strokes (1/218 [0.5%] vs 10/226 [4.0%], OR=0.14 [95% CI 0.02-0.61], p=0.012) and more bleeding events (2 vs 0). Conclusion/Relevance: This IPD analysis of all currently available RCT data found no significant difference between anticoagulants and antiplatelets in preventing early recurrent events. Trial Registration: Our IPD meta-analysis is registered in PROSPERO (CRD42023372742).This research project as a doctoral thesis was funded by the Goldschmidt-Jacobson foundation. The CADISS study was supported by a project grant from the Stroke Association, and recruitment was supported by the English National Institute for Health Research Stroke Research Network. The TREAT-CAD trial was funded by Swiss National Science Foundation (grant 140340), Swiss Heart Foundation, Stroke Funds Basel, University Hospital Basel, University of Basel, and Academic Society Basel, and we gratefully acknowledge the work of the data safety monitoring board and the clinical event adjudicators. The Stroke Research Group at the University of Cambridge has received funding from the Cambridge British Heart Foundation Centre of Research Excellence (RE/18/1/34212) and a British Heart Foundation programme grant (RG/F/22/110052), and infrastructural support was provided by the Cambridge University Hospitals NIHR Biomedical Research Centre (IS-BRC-1215-20014). ELH is funded by the Alzheimer’s Society (AS-RF-21-017). The views expressed in this publication are those of the authors and not necessarily those of the NIHR, NHS, or UK Department of Health and Social Care

Once versus twice daily direct oral anticoagulants in patients with recent stroke and atrial fibrillation.

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