Rationale and design of the impact of anticoagulation therapy on the Cognitive Decline and Dementia in Patients with Nonvalvular Atrial Fibrillation (CAF) Trial: A Vanguard study.
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SUBMITTER: Bunch TJ
PROVIDER: S-EPMC6522997 | biostudies-literature | 2019 May
REPOSITORIES: biostudies-literature
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Project description:BackgroundAtrial fibrillation (AF) is associated with a risk for cognitive impairment and dementia, which is more pronounced in patients with a history of clinical stroke. Anticoagulation use and efficacy impact long-term risk of dementia in AF patients in observational trials.MethodsThe cognitive decline and dementia in patients with non-valvular atrial fibrillation (CAF) Trial was a randomized, prospective, open-label vanguard clinical study with blinded endpoint assessment involving patients with moderate- to high-risk (CHADS2 or CHA2DS2-Vasc scores of ≥2) non-valvular AF assigned to dabigatran etexilate or warfarin. The primary endpoint was incident dementia or moderate cognitive decline at 24 months.ResultsA total of 101 patients were enrolled [mean age:73.7 ± 6.0 years, male: 54(53.5%)]. Prior stroke and stroke risk factors were similar between groups. Average INR over the study was 2.41 ± 0.68 in the warfarin group. No patient experienced a stroke or developed dementia. Mini-Mental Status Evaluation, Hachinski Ischemic scale, cognitive subscale of the Alzheimer's Disease Assessment Scale, Disability Assessment for Dementia, Quality of Life Improvement as assessed by Minnesota Living with Heart Failure Scale and the Anti-Clot Treatment Scale Quality of Life Survey scores did not vary at baseline or change over 2 years. Biomarker analysis indicated a similar efficacy of anticoagulation strategies.ConclusionUse of dabigatran and well-managed warfarin therapy were associated with similar risks of stroke, cognitive decline, and dementia at 2 years, suggestive that either strategy is acceptable. The results of this Vanguard study did not support the pursuit of a larger formally powered study.
| S-EPMC9745454 | biostudies-literature
Project description:Background/objectivesOral anticoagulation (OAC) is challenging in older patients with nonvalvular atrial fibrillation (NVAF) who are often frail and have cognitive impairment. We examined the characteristics of older NVAF patients associated with higher odds of physical and cognitive impairments. We also examined if these high-risk patients have different OAC prescribing patterns and their satisfaction with treatment because it may impact optimal management of their NVAF.MethodsThe patients in the Systematic Assessment of Geriatric Elements in Atrial Fibrillation (SAGE-AF study cohort 2016-2018) had NVAF, were aged 65 and older, and eligible for the receipt of OAC. Measures included frailty (Fried Frailty scale), cognitive impairment (Montreal Cognitive Assessment Battery), OAC prescribing and type (direct oral anticoagulant [DOAC] or vitamin K antagonist [VKA]), depressive symptoms (Patient Health Questionnaire-9), bleeding, stroke risk, and treatment benefit (Anti-Clot Treatment Scale).ResultsPatients (n = 1,244) were 49% female, aged 76 (standard deviation = 7) years. A total of 14% were frail, and 42% had cognitive impairment. Frailty and cognitive impairment co-occurred in 9%. Odds of having both impairments versus none were higher with depression (odds ratio [OR] = 4.62; 95% confidence interval [CI] = 2.59-8.26), older age (OR = 1.56; 95% CI = 1.29-1.88), lower education (OR = 3.81; 95%CI = 2.13-6.81), race/ethnicity other than non-Hispanic White (OR = 7.94; 95% CI = 4.34-14.55), bleeding risk (OR = 1.43; 95% CI = 1.12-1.81), and stroke risk (OR = 1.35; 95% CI = 1.13-1.62). OAC prescribing was not associated with CI and frailty status. Among patients taking OACs (85%), those with both impairments were more likely to take DOAC than VKA (OR = 1.69; 95% CI = 1.01-2.80). Having both impairments (OR = 1.87; 95% CI = 1.08-3.27) or cognitive impairment (OR = 1.56; 95% CI = 1.09-2.24) was associated with higher odds of reporting lower treatment benefit.ConclusionIn a large cohort of older NVAF patients, half were frail or cognitively impaired, and 9% had both impairments. We highlight the characteristics of patients who may benefit from cognitive and physical function screenings to maximize treatment and enhance prognosis. Finally, the co-occurrence of impairment was associated with low perceived benefit of treatment that may impede optimal management.
| S-EPMC8567309 | biostudies-literature
Project description:Three target-specific oral anticoagulants (TSOACs)-dabigatran, rivaroxaban, and apixaban-have been approved by the FDA to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation; however, no agents are currently approved to reverse the anticoagulant effects of these TSOACs in cases of active bleeding. This review discusses the benefits and risks of these TSOACs from a clinician's perspective, with a focus on the interruption of treatment for either elective or emergent surgery, monitoring, and reversal of anticoagulation. Available coagulation assays are not ideal for monitoring the effects of TSOACs and do not provide reliable quantitative measurement of their anticoagulant effects. When necessary, activated partial thromboplastin time (aPTT) may provide qualitative information on dabigatran, and prothrombin time (PT) may provide qualitative assessment of the presence of the factor Xa inhibitors, rivaroxaban and apixaban. Current recommendations for reversal of TSOACs are based largely on limited and sometimes conflicting data from in vitro or in vivo animal models, and clinical experience with these recommendations is also limited. Methods that have been investigated for effectiveness for reversal of the pharmacodynamic effects of the TSOACs include dialysis, activated charcoal, prothrombin complex concentrate (PCC), and recombinant activated factor VII. It is important to note that even within a class of anticoagulant drugs, compounds respond differently to reversal agents; therefore, recommendations for one agent should not be extrapolated to another, even if they are from the same therapeutic class. New antidotes are being explored, including a mouse monoclonal antibody to dabigatran; andexanet alfa, a potential universal factor Xa inhibitor reversal agent; and a synthetic small molecule (PER977) that may be effective for the reversal of factor Xa inhibitors and direct thrombin inhibitors. Given the short half-lives of TSOACs, watchful waiting, rather than reversal, may be the best approach in some circumstances.
| S-EPMC4264672 | biostudies-literature
Project description:Purpose of Review:Atrial fibrillation (AF) and dementia are both prevalent diseases in aging societies, which exert a great economic burden worldwide. Although a handful of epidemiologic studies have indicated that AF is independently associated with faster cognitive decline and a higher risk of dementia, there is still a lack of comprehensive understanding of the observed association. In this review, we summarize evidence from major epidemiologic studies concerning AF-related cognitive decline and dementia, the potential mechanisms underlying their association, and the cognitive benefits of treatment options. Recent Findings:A large majority of population-based longitudinal studies have consistently shown an independent association of AF with cognitive decline and dementia with varying effect sizes, depending on the age of the study population and the presence of clinical stroke. The underlying pathways linking AF to cognitive phenotypes may involve systemic inflammation, cerebral hypoperfusion, and cerebral small vessel disease and microemboli. However, current evidence is insufficient to support the potential benefits of AF treatment in reducing risk of cognitive decline and dementia. Summary:Current epidemiologic research suggests that AF contributes to cognitive decline and dementia, independent of a history of stroke. Further work is warranted to elucidate the potential mechanisms underlying this association, and more well-designed studies are needed to explore the possible cognitive benefits of different therapeutic options in patients with AF.
| S-EPMC6096854 | biostudies-literature
Project description:BackgroundBridging anticoagulation is commonly prescribed to patients with atrial fibrillation during initiation and interruption of warfarin. Guidelines recommend bridging patients at high risk of stroke, while a recent randomized trial demonstrated overall harm in a population at comparatively low risk of ischemic stroke. Theory suggests that patients at high risk of stroke and low risk of hemorrhage may benefit from bridging, but data informing patient selection are scant.ObjectiveTo estimate the utility and cost-effectiveness of bridging anticoagulation among patients with nonvalvular atrial fibrillation, stratified by thromboembolic and hemorrhagic risk DESIGN: Cost-effectiveness analysis with lifelong time horizon, from the perspective of a third-party payer MAIN MEASURES: Quality-adjusted life years (QALYs) per bridged patient; US dollars per QALY gained KEY RESULTS: Unselected patients with nonvalvular atrial fibrillation may be harmed by bridging anticoagulation. Hospital admission for bridging is almost never cost-effective, and generally harmful. Among patients carefully selected by both thromboembolic and hemorrhagic risks, outpatient bridging can be beneficial and cost-effective. Results were sensitive to how effectively heparin products reduce stroke risk.ConclusionsOutpatient bridging anticoagulation can be beneficial and cost-effective for a subset of patients with nonvalvular atrial fibrillation during interruption or initiation of warfarin. Admission for bridging should be avoided.
| S-EPMC6445930 | biostudies-literature
Project description:BackgroundIt is well known that atrial fibrillation (AF) carried a high risk of cognitive decline, which is independent of stroke or transient ischemic attack (TIA). Whether anticoagulation is associated with reduced risk of cognitive decline in participants with AF still remains controversial. We conducted a systematic review and meta-analysis to explore the effect of anticoagulation on the risk of cognitive decline in patients with AF.MethodsWe systematically searched the PubMed, Embase and the Cochrane Database for eligible studies published up to January 2018. Risk ratios (RR) with 95% confidence interval (CI) for cognitive decline were extracted, and pooled estimations were calculated using the fixed effects model. Subgroup analyses were further performed.ResultsEight relevant articles involved 454,273 patients were ultimately included in this meta-analysis. We found that anticoagulation was associated with reduced risk of cognitive impairment as compared with nonanticoagulation (RR 0.72, 95% CI 0.69-0.75, I 11.5%). This reduction was still significant after adjustment for stroke and TIA (RR 0.72, 95% CI 0.69-0.74, I 0.0%). In the subgroup analyses, the incidence of cognitive decline was significantly decreased in those treated with anticoagulation compared to no treatment (RR 0.72, 95% CI 0.69-0.75, I 0.0%), but the cognitive benefit showed no significant difference between anticoagulant and antiplatelet treatment (RR 1.01, 95% CI 0.68-1.50, I 46.8%).ConclusionAnticoagulation is associated with cognitive benefit in participants with AF independent of stroke and TIA, but it was not superior to antiplatelet drugs in reducing the risk of cognitive decline.
| S-EPMC6408007 | biostudies-literature
Project description:AimsTo assess whether AF is a risk factor for cognitive dysfunction we used prospective data on AF, repeat cognitive scores, and dementia incidence in adults followed over 45 to 85 years.Methods and resultsData are drawn from the Whitehall II study, N = 10 308 at study recruitment in 1985. A battery of cognitive tests was administered four times (1997-2013) to 7428 participants (414 cases of AF), aged 45-69 years in 1997. Compared with AF-free participants, those with longer exposure to AF (5, 10, or 15 years) experienced faster cognitive decline after adjustment for sociodemographic, behavioural, and chronic diseases (P for trend = 0.01). Incident stroke or coronary heart disease individually did not explain the excess cognitive decline; however, this relationship was impacted when considering them together (P for trend 0.09). Analysis of incident dementia (N = 274/9302 without AF; N = 50/912 with AF) showed AF was associated with higher risk of dementia in Cox regression adjusted for sociodemographic factors, health behaviours and chronic diseases [hazard ratio (HR): 1.87; 95% confidence interval (CI): 1.37, 2.55]. Multistate models showed AF to increase risk of dementia in those free of stroke (HR: 1.67; 95% CI: 1.17, 2.38) but not those free of stroke and coronary heart disease (HR: 1.29; 95% CI: 0.74, 2.24) over the follow-up.ConclusionIn adults aged 45-85 years AF is associated with accelerated cognitive decline and higher risk of dementia even at ages when AF incidence is low. At least in part, this was explained by incident cardiovascular disease in patients with AF.
| S-EPMC5837240 | biostudies-literature
Project description:BackgroundBridging anticoagulation is commonly prescribed to patients with atrial fibrillation who are initiating warfarin or require interruption of anticoagulation. Current guidelines recommend bridging for patients at high risk of stroke. Among patients with atrial fibrillation and one or more risk factors for ischemic stroke, the recently published BRIDGE trial found forgoing bridging during interruption to be, on average, noninferior to bridging with respect to ischemic complications, with significantly fewer hemorrhagic complications.ObjectiveWe sought to examine the benefits and harms of bridging anticoagulation across the spectrum of ischemic and hemorrhagic stroke risk and thereby enable more nuanced, risk-stratified decision-making when bridging is considered during initiation or interruption of vitamin K antagonists.DesignA Monte Carlo simulation, using a combination of literature-derived estimates, registry data, and trial data.Main measuresNet clinical benefit, weighting for ischemic strokes, intracranial hemorrhages, and extracranial major hemorrhages.Key resultsThe benefits and harms of bridging anticoagulation vary according to underlying patient risk profiles for both thromboembolic stroke and major intracranial bleeding. Patients at high risk of ischemic stroke and low risk of hemorrhage derive benefit from bridging during initiation or interruption of warfarin therapy. Patients at similarly high or low risk of both outcomes may receive benefit from bridging during initiation and bridging during interruption, but this was sensitive to underlying assumptions. The need for stratification along both axes of risk was robust to a wide range of parameters.ConclusionsBridging anticoagulation may provide benefit to patients at high risk of ischemic stroke and low risk of intracranial hemorrhage who are initiating or interrupting warfarin therapy, while patients at high or low risk of both complications may be harmed. The use of bridging anticoagulation in patients with non-valvular atrial fibrillation should be considered only after stratification by risk of ischemic and hemorrhagic complications.
| S-EPMC5377884 | biostudies-literature
Project description:Patients with atrial fibrillation (AF) are at increased thromboembolic risk, and they suffer more severe strokes with worse outcomes. Most thromboembolic complications of AF are eminently preventable with oral anticoagulation, and the increasing numbers of AF patients mean antithrombotic therapy is the most crucial management aspect of this common arrhythmia. Despite the proven efficacy of warfarin, a string of limitations have meant that it is underused by physicians and patients alike. This has prompted a search for new anticoagulants that could overcome many of the inconveniences of dose variability and anticoagulant monitoring associated with warfarin, but without sacrificing efficacy in thromboprophylaxis. The arrival of new oral anticoagulants has been complemented by improved risk stratification schemes, which permit clinicians to easily and reliably identify patients requiring anticoagulation and their bleeding risk. These advances in AF treatment will hopefully translate into improved outcomes for patients, especially as our experience with the new agents grows.
| S-EPMC4711491 | biostudies-other
Project description:Background: Oral anticoagulants (OACs) are essential for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). However, the appropriateness of anticoagulation treatment in locally practice remains unclear. This study evaluated compliance with anticoagulation therapy concerning the guidelines and drug labels in patients with NVAF. Methods: Hospitalized patients diagnosed with NVAF between 1 November 2020, and 31 December 2021, were retrospectively enrolled. The appropriateness of anticoagulation regimens at discharge was evaluated based on a flowchart designed according to atrial fibrillation (AF) guidelines and medication labels. Furthermore, we explored factors potentially influencing the "no-use of OACs" using binary logistic regression and verified anticoagulation-related issues through a physician questionnaire. Results: A total of 536 patients were enrolled in this study, including 254 patients (47.4%) with inappropriate anticoagulation regimens. 112 patients (20.9%) were categorized as "underdosing-use of OACs," 134 (25%) who needed anticoagulation therapy were "no-use of OACs" and eight (1.5%) were "over-use of OACs." The results of a binary logistic regression analysis showed that paroxysmal AF (odds ratio [OR], 7.74; 95% confidence interval [CI], 4.57-13.10), increased blood creatinine levels (OR, 1.88; 95% CI, 1.11-3.16), hospitalized pacemaker implantation (OR, 6.76; 95% CI, 2.67-17.11), percutaneous coronary intervention (OR, 3.35; 95% CI, 1.44-7.80), and an increased HAS-BLED score (OR, 1.62; 95% CI, 1.11-2.35) were associated with "no-use of OACs" in patients with NVAF who had indications for anticoagulation therapy. Conclusion: For patients with NVAF with severe renal dysfunction and paroxysmal AF, anticoagulation therapy was inadequate. The underdosing-use of OACs in patients with NVAF was frequently observed. We recommend an anticoagulation management team to tailor anticoagulation regimens to suit each patient's needs.
| S-EPMC10728771 | biostudies-literature