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Summary of evidence-based guideline update: Prevention of stroke in nonvalvular atrial fibrillation: Report of the Guideline Development Subcommittee of the American Academy of Neurology

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... The detection rate of AF in patients with CS remains relatively low in large-scale population studies (7). Current guidelines recommend extending the duration of ECG monitoring by 1 week and beyond to improve AF detection (8). Due to limited healthcare resources at all levels, it is impossible to sequentially use all cardiac monitoring techniques for real-time follow-up of patients during hospitalization and after discharge. ...
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Background Atrial fibrillation detected after stroke (AFDAS) is associated with an increased risk of ischemic stroke (IS) recurrence and death. Early diagnosis can help identify strategies for secondary prevention and improve prognosis. However, there are no validated predictive tools to assess the population at risk for AFDAS. Therefore, this study aimed to develop and validate a predictive model for assessing the incidence of AFDAS after acute ischemic stroke (AIS). Methods This study was a multicenter retrospective study. We collected clinical data from 5332 patients with AIS at two hospitals between 2014.01 and 2021.12 and divided the development and validation of clinical prediction models into a training cohort (n = 3173) and a validation cohort (n = 2159). Characteristic variables were selected from the training cohort using the least absolute shrinkage and selection operator (LASSO) algorithm and multivariable logistic regression analysis. A nomogram model was developed, and its performance was evaluated regarding calibration, discrimination, and clinical utility. Results We found the best subset of risk factors based on clinical characteristics and laboratory variables, including age, congestive heart failure (CHF), previous AIS/transient ischemia attack (TIA), national institutes of health stroke scale (NIHSS) score, C-reactive protein (CRP), and B-type natriuretic peptide (BNP). A predictive model was developed. The model showed good calibration and discrimination, with calibration values of Hosmer-Lemeshow χ² = 4.813, P = 0.732 and Hosmer-Lemeshow χ² = 4.248, P = 0.834 in the training and validation cohorts, respectively. The area under the ROC curve (AUC) was 0.815, 95% CI (0.777–0.853) and 0.808, 95% CI (0.770–0.847). The inclusion of neuroimaging variables significantly improved the performance of the integrated model in both the training cohort (AUC. 0.846 (0.811–0.882) vs. 0.815 (0.777–0.853), P = 0.001) and the validation cohort (AUC: 0.841 (0.804–0.877) vs. 0.808 (0.770–0.847), P = 0.001). The decision curves showed that the integrated model added more net benefit in predicting the incidence of AFDAS. Conclusion Predictive models based on clinical characteristics, laboratory variables, and neuroimaging variables showed good calibration and high net clinical benefit, informing clinical decision-making in diagnosing and treating patients with AFDAS.
... Moreover, we discovered multiple differences in known therapeutic target genes of brain, vascular and autoimmune disorders, predicting involvement of the corresponding transcripts in the AD cognitive decline. For example, the G protein-coupled receptor gene P2RY12 is elevated in AD and interestingly is implicated in peripheral and cerebrovascular diseases (Culebras et al., 2014), reminiscent of apolipoprotein E that controls cerebrovascular integrity in healthy individuals and fails to do so in AD patients (Bell et al., 2012). The P2RY12targeting drug Clopidogrel (Pfizer) is chronically administered to acute coronary syndrome patients. ...
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Alzheimer's disease (AD) involves changes in both lipid and RNA metabolism, but it remained unknown if these differences associate with AD's cognition and/or post-mortem neuropathology indices. Here, we report RNA-sequencing evidence of inter-related associations between lipid processing, cognition level, and AD neuropathology. In two unrelated cohorts, we identified pathway-enriched facilitation of lipid processing and alternative splicing genes, including the neuronal-enriched NOVA1 and hnRNPA1. Specifically, this association emerged in temporal lobe tissue samples from donors where postmortem evidence demonstrated AD neuropathology, but who presented normal cognition proximate to death. The observed changes further associated with modified ATP synthesis and mitochondrial transcripts, indicating metabolic relevance; accordingly, mass-spectrometry-derived lipidomic profiles distinguished between individuals with and without cognitive impairment prior to death. In spite of the limited group sizes, tissues from persons with both cognitive impairment and AD pathology showed elevation in several drug-targeted genes of other brain, vascular and autoimmune disorders, accompanied by pathology-related increases in distinct lipid processing transcripts, and in the RNA metabolism genes hnRNPH2, TARDBP, CLP1 and EWSR1. To further detect 3′-polyadenylation variants, we employed multiple cDNA primer pairs. This identified variants that showed limited differences in scope and length between the tested cohorts, yet enabled superior clustering of demented and non-demented AD brains versus controls compared to total mRNA expression values. Our findings indicate inter-related cognition-associated differences in AD's lipid processing, alternative splicing and 3′-polyadenylation, calling for pursuing the underlying psychological and therapeutics implications.
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Background and purpose: Patients with nonvalvular atrial fibrillation (NVAF) who survive an intracranial hemorrhage (ICH) have an increased risk of ischemic stroke and systemic embolism (IS/ SE). We investigated whether starting oral anticoagulants (OACs) among older NVAF patients after an ICH was associated with a lower risk of IS/SE and mortality but offset by an increase in major bleeding. Methods: We assembled a patient cohort from the Quebec Régie de l'Assurance Maladie du Québec (RAMQ) and Med-Echo administrative databases. We identified older adults with NVAF from 1995 to 2015. All patients with incident ICH and discharged in community were included. Patients were categorized according to OAC exposure. Outcomes included IS/SE, all-cause mortality, recurrent ICH and major bleeding after a quarantine period of 6 weeks. Crude event rates were calculated at 1-year of follow-up, and Cox proportional hazard models with a time-dependent binary exposure were used to assess adjusted hazard ratios (AHRs). Results: The cohort of 683 NVAF patients with ICH aged 83 years on average. The rates (per 100 person-years) for IS/SE, death, ICH and major bleeding were 3.3, 40.6, 11.4, and 2.7 for the no OAC group; and 2.6, 16.3, 5.2, and 5.2 for OAC group, respectively. The AHR for IS/SE and death was 0.10 (95% confidence interval [CI], 0.05 to 0.21), 0.43 (95% CI, 0.19 to 0.97) for recurrent ICH and 1.73 (95% CI, 0.71 to 4.20) for major extracranial bleeding comparing OAC exposure to non-exposed. Conclusions: Initiating OAC after ICH in older individuals with NVAF is associated with a reduction of IS/SE and mortality and a trend in recurrent ICH supporting its use after ICH.
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Approximately one third of ischemic strokes are labeled cryptogenic because the etiology is unknown despite a thorough evaluation. Paroxysmal atrial fibrillation carries the same risk of ischemic stroke as persistent atrial fibrillation and has increasingly gained attention as a potential source of cryptogenic stroke. Recent trials utilizing long-term cardiac monitoring devices have demonstrated high rates of previously undetected paroxysmal atrial fibrillation in patients with cryptogenic stroke. Newly detected atrial fibrillation has subsequently changed treatment and increased the use of oral anticoagulation in these studies. Other trials have shown an increased risk of stroke and thromboembolism in patients with device-detected subclinical tachyarrhythmias. Together, these studies suggest an important relationship between episodes of paroxysmal atrial fibrillation and the risk of cryptogenic stroke, but further investigations are needed to guide diagnostic and therapeutic decisions.
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Atrial fibrillation (AF) puts patients at risk of complications, including stroke. Warfarin therapy has been the mainstay of antithrombotic treatment for reducing the risk of stroke in AF. However, warfarin has limitations that have motivated development of several novel oral anticoagulants (NOACs), including dabigatran, rivaroxaban, apixaban, and edoxaban. Clinical trials demonstrate that the NOACs offer efficacy and safety that are equivalent to, or better than, those of warfarin for reducing the risk of stroke in patients with nonvalvular AF. This review examines stroke risk reduction in patients with AF from the perspective of the clinician balancing the risks and benefits of treatment options, evaluates the most recent guidelines, and discusses 2 hypothetical patient cases to better illustrate how clinicians may apply available data in the clinical setting. We reviewed guidelines for the reduction of stroke risk in AF and data from clinical trials on the NOACs. Choosing antithrombotic treatment involves assessing the benefits of therapy versus its risks. Risk indexes, including CHADS2, CHA2DS2-VASc, and HAS-BLED can help determine how to treat patients with AF. Current guidelines suggest using these risk indexes to customize treatment to individual patients. Many current treatment guidelines also incorporate recommendations for the use of NOACs as an alternative to warfarin. As additional data emerge and guidelines are updated, these recommendations will likely evolve. In the interim, clinicians may consider published guidelines and clinical trial results on NOACs. Real-world experience will provide clinicians with additional insight into their treatment decisions.
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Fragestellung: Was hat sich durch die Zulassung neuer NOAC (orale direkte Antikoagulanzien) an den Therapieleitlinien zur Schlaganfallprävention bei Vorhofflimmern geändert?Hintergrund: Die letzte Leitlinie der American Academy of Neurology (AAN) zur Schlaganfallprävention bei nicht valvulärem Vorhofflimmern datiert aus dem Jahr 1998. Die Ergebnisse der großen Studien zu den NOAC bei nicht valvulärem Vorhofflimmern machte es notwendig, die Leitlinien zu aktualisieren.Patienten und Methodik: Die Autoren führten eine systematische Literaturrecherche durch und begründen ihre Therapieempfehlungen mit den Ergebnissen großer randomisierter Studien. Die Therapieempfehlungen werden zusammenfassend dargestellt.Ergebnisse: 1. Bei Patienten mit kryptogenem Schlaganfall kann ein EKG-Monitoring klinisch stummes Vorhofflimmern mit einer durchschnittlichen Wahrscheinlichkeit von 11% entdecken.2. Patienten mit Vorhofflimmern wird eine orale Antikoagulation empfohlen. Wird Warfarin eingesetzt, sollte d ...
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Secondary stroke prevention in the elderly in many cases requires the use of drug therapy to maximize risk factor control. However, the elderly (≥65 years) are most likely to receive care that is not evidence-based, because of concerns for adverse events. In this review, we provide evidence to the practitioner in support of the value of blood pressure control with drug therapy to decrease recurrent stroke risk. This review also highlights evidence for the importance of statin therapy in stroke prevention among the elderly. Finally, the appropriate use of antiplatelet therapy and oral anticoagulation is addressed.
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To update the 1998 American Academy of Neurology practice parameter on stroke prevention in nonvalvular atrial fibrillation (NVAF). How often do various technologies identify previously undetected NVAF? Which therapies reduce ischemic stroke risk with the least risk of hemorrhage, including intracranial hemorrhage? The complete guideline on which this summary is based is available as an online data supplement to this article. Systematic literature review; modified Delphi process recommendation formulation. In patients with recent cryptogenic stroke, cardiac rhythm monitoring probably detects occult NVAF. In patients with NVAF, dabigatran, rivaroxaban, and apixaban are probably at least as effective as warfarin in preventing stroke and have a lower risk of intracranial hemorrhage. Triflusal plus acenocoumarol is likely more effective than acenocoumarol alone in reducing stroke risk. Clopidogrel plus aspirin is probably less effective than warfarin in preventing stroke and has a lower risk of intracranial bleeding. Clopidogrel plus aspirin as compared with aspirin alone probably reduces stroke risk but increases the risk of major hemorrhage. Apixaban is likely more effective than aspirin for decreasing stroke risk and has a bleeding risk similar to that of aspirin. Clinicians might obtain outpatient cardiac rhythm studies in patients with cryptogenic stroke to identify patients with occult NVAF (Level C) and should routinely offer anticoagulation to patients with NVAF and a history of TIA/stroke (Level B). Specific patient considerations will inform anticoagulant selection in patients with NVAF judged to need anticoagulation.
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To determine whether low-dose aspirin or warfarin induces fecal occult blood loss. A prospective, cross-over study, of 100 participants over 40 years of age in 1 of 3 groups, taking: (1) no aspirin or warfarin, (2) daily aspirin (either 81 or 325 mg), or (3) warfarin, but no aspirin. Stool samples were collected and analyzed for the presence of occult blood using HemoQuant and Hemoccult II. After collection of baseline samples, patients initially taking no aspirin (group 1) were asked to take regular aspirin (325 mg daily) for 2 months. Patients initially taking aspirin 81 mg daily (group 2) were switched to 325 mg daily for 2 months, and vice versa. Patients taking no aspirin had mean fecal blood of 0.68 +/- 0.05 mg hemoglobin/g stool, which increased to 1.41 +/- 0.36 mg/g after taking 325 mg of aspirin daily (P = 0.02). In contrast, patients in group 2, taking 81 mg and 325 mg of aspirin, had mean fecal blood of 0.82 +/- 0.08 mg/g (P = 0.57) and 1.04 +/- 0.23 mg/g (P = 0.13), respectively (comparisons with patients taking no aspirin). The mean blood loss in patients taking warfarin was 0.51 +/- 0.04 mg/g (P = 0.55), and fecal blood was not related to the degree of anticoagulation. There was no increase over normal in the rate of Hemoccult II-positive stool tests with aspirin or warfarin therapy. Aspirin, but not warfarin, caused a small but clinically insignificant increase in occult fecal blood. The small blood loss in patients taking aspirin or warfarin is unlikely to interfere with fecal occult blood test. Therefore, positive fecal occult blood tests, in patients taking either low-dose aspirin or warfarin, should be managed in the same fashion as patients not taking these medications.
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This trial evaluated the efficacy and safety of the combination of antiplatelet and moderate-intensity anticoagulation therapy in patients with atrial fibrillation associated with recognized risk factors or mitral stenosis. Warfarin was more effective than aspirin in preventing stroke in these patients; combined therapy with low anticoagulant intensity was ineffective. Mitral stenosis patients were not investigated. We performed a multicenter randomized trial in 1,209 patients at risk. The intermediate-risk group included patients with risk factors or age >60 years: 242 received the cyclooxygenase inhibitor triflusal, 237 received acenocumarol, and 235 received a combination of both. The high-risk group included patients with prior embolism or mitral stenosis: 259 received anticoagulants and 236 received the combined therapy. Median follow-up was 2.76 years. Primary outcome was a composite of vascular death and nonfatal stroke or systemic embolism. Primary outcome was lower in the combined therapy than in the anticoagulant arm in both the intermediate- (hazard ratio [HR] 0.33 [95% confidence interval (CI)0.12 to 0.91]; p = 0.02) and the high-risk group (HR 0.51 [95% CI 0.27 to 0.96]; p = 0.03). Primary outcome plus severe bleeding was lower with combined therapy in the intermediate-risk group. Nonvalvular and mitral stenosis patients had similar embolic event rates during anticoagulant therapy. The combined antiplatelet plus moderate-intensity anticoagulation therapy significantly decreased the vascular events compared with anticoagulation alone and proved to be safe in atrial fibrillation patients.
Article
Patients with nonvalvular atrial fibrillation are at increased risk for systemic embolism, predominantly disabling stroke. To study how stroke and mortality rates vary with different degrees of anticoagulation reflected by the international normalised ratio (INR) we critically assess information from different sources. 1. Computerized search of the medical literature published between 1980 and July 2004 was performed using MEDLINE applied to various combinations of the search terms of atrial fibrillation, warfarin, anticoagulation, anticoagulation intensity, and INR, not restricted by language. 2. We performed a record linkage analysis with death hazard estimated as a continuous function of INR based on 21,967 patients. Similarly the risk of admission to hospital or death due to diseases of the vessels of the brain was estimated. 3. Re-analysis of data earlier published by Hylek et al. from year 2003. 1. One randomised study showed a significantly lower risk of stroke for mean INR 2.4 compared to mean INR 1.3 combined with aspirin. Remaining studies found INRs of 2-2.5 to be as efficacious as higher anticoagulation intensities.2. Mortality as well as risk of admission to hospital or death due to diseases of the vessels of the brain followed U-shaped curves with minimum at INR 2.2 and 2.4, respectively. At high INR the risk increased 2.3 times per 1 unit increase of INR for death and 1.7 times for events in the vessels of the brain.3. The re-analysing of data of Hylek et al. indicated that there might be a substantial increase of the risk of intracranial hemorrhage when INR is increased from 2.5 to 4. We conclude that INRs in the interval 2.0--2.5 give the lowest risk of stroke and death in patients with nonvalvular atrial fibrillation.