Atrial Fibrillation-associated Stroke Research Articles

Bleeding events in the emergency department with warfarin versus novel oral anticoagulants: A five-year analysis.

Although warfarin is the most effective treatment approved to prevent atrial fibrillation-associated stroke, it remains underused in clinical practice due to patient noncompliance. Therefore, novel oral anticoagulants (NOACs) have been developed. This study aimed to identify bleeding complications in patients who were taking oral anticoagulants and compare the rates of major and minor bleeding events between NOACs and warfarin groups. We conducted a retrospective, observational study of warfarin- and NOAC-treated patients who presented to an emergency department between January 2015 and December 2019 with bleeding events. We compared patients with major and minor bleeding in terms of age, gender, comorbid diseases, type of anticoagulant, and site of bleeding. An electronic search yielded 95 (21.9%) cases of patients taking a NOAC (i.e., dabigatran [19], rivaroxaban [45], apixaban [29], or edoxaban [6]) and 354 taking warfarin. There were no significant differences between the warfarin and NOACs groups in the frequency of minor bleeding complications. Similarly, there were no significant differences between the groups in the frequency of major bleeding complications. No significant difference in intracranial bleeding was seen between the NOACs- and warfarin-treated patients, although the incidence of gastrointestinal bleeding was significantly higher in the NOACs (P = 0.102 and P = 0.021, respectively). Our findings indicate that rates of major and minor bleeding complications in patients taking NOACs are similar to those in patients taking warfarin. While warfarin was associated with fewer complications than NOACs in terms of gastrointestinal bleeding, the risk of intracranial bleeding, was similar between the groups.

Prestroke Statins Improve Prognosis of Atrial Fibrillation-Associated Stroke through Increasing Suppressor of Cytokine Signaling-3 Levels

Background: Cerebral infarction associated with atrial fibrillation (AF) has relatively higher mortality and morbidity rates than other types of stroke. Statins are being commonly prescribed to patients with stoke. However, the use of statins in AF-related stroke, especially prestroke, has not been well studied. This study aimed to investigate whether the use of prestroke statins could improve clinical outcomes in patients with AF-related acute ischemic stroke (AIS) and its mechanism. Methods: This prospective study enrolled 453 AF-associated AIS patients from 4 medical centers and divided them into 2 groups based on the statin use before the stroke episode. All patients received comprehensive clinical examinations including 72-h Holter electrocardiogram monitoring and were followed up for 3 months. Plasma suppressor of cytokine signaling-3 (SOCS-3) and matrix metalloproteinase-9 (MMP-9) levels were measured by ELISA on admission and days 3 and 7 after enrollment. The endpoints were death, major disability (modified Rankin Scale score ≥3), and composite outcome (death/major disability) at 3 months after the AIS episode. Results: Plasma SOCS-3 levels were significantly increased and MMP-9 levels decreased in patients in the prestroke statin group on hospital admission and days 3 and 7 after enrollment (p < 0.001). Furthermore, our data suggested that baseline plasma SOCS-3 levels were associated with increased risk of 3-month mortality (adjusted odds ratio [OR], 1.012; 95% confidence interval [CI], 1.006–1.018; p < 0.001) and major disability (adjusted OR, 1.013; 95% CI, 1.007–1.02; p < 0.001). Similarly, baseline plasma MMP-9 levels were also associated with increased risk of 3-month mortality (adjusted OR, 1.037; 95% CI, 1.022–1.053; p < 0.001) and major disability (adjusted OR, 1.038; 95% CI, 1.022–1.55; p < 0.001). Conclusion: Our data suggested that the prestroke use of statins improved the clinical outcomes in AIS patients with AF by upregulating the level of SOCS-3 and reducing the plasma MMP-9 level.

Eight-Section Brocade Exercises Improve the Sleep Quality and Memory Consolidation and Cardiopulmonary Function of Older Adults With Atrial Fibrillation-Associated Stroke.

Purpose: Poor sleep quality is harmful for everyone and potentially even more harmful for older adults with atrial fibrillation-associated stroke (AFAS). This study aims to explore the effects of eight-section brocade (ESB) on sleep quality, memory, and cardiopulmonary function in the older adults with AFAS.Methods: Older adults with AFAS and sleep disorders were recruited and divided into the ESB (EG, n = 85) and control groups (CG, general exercise, n = 85). EG patients received 60 min ESB exercises 5 times a week for 12 weeks; CG patients received normal exercise. Pittsburgh sleep quality index (PSQI) scores (poor sleepers ≥8 and normal sleepers < 8), memory for word pairs (poor memory ≤ 7 and normal memory > 7), left ventricular posterior wall (LVPW) thickness, and maximum ventilation (MV, to evaluate cardiopulmonary function) values were measured. The correlation between sleep and memory quality was analyzed using PSQI scores and word pairs via the Pearson correlation coefficients test. Adjusted Cox models were used to explore an interaction between PSQI and ESB exercise.Results: After 12-week exercise intervention, ESB improved sleep quality, latency, duration, disturbance and daytime dysfunction when compared to conventional exercise. In similar cases, the MV values in the EG were also higher than that in the CG (p = 0.009). ESB intervention could not affect the cardiac structure and left ventricular ejection fraction. Compared with the CG, the ESB intervention reduced PSQI scores and increased memorized word pairs (p < 0.001 for poor and normal sleepers in both unadjusted and adjusted analysis, p = 0.012 and 0.003 for poor and normal memory). The test of Pearson correlation coefficients showed that PSQI scores were strongly associated with the number of word pairs in both unadjusted and adjusted analyses (p < 0.0001).Conclusion: Eight-section brocade exercise improved sleep quality and memory consolidation and cardiopulmonary function by reducing PSQI scores, increasing word pairs and MV values in the older adults with AFAS.

Time Trends in Atrial Fibrillation-Associated Stroke and Premorbid Anticoagulation: Population-Based Study and Systematic Review.

Background and Purpose- Prevalence of atrial fibrillation (AF) is increasing, but the impact on overall burden of stroke is uncertain, as is the proportion that could be attributed to under anticoagulation. We did a population-based study of AF-associated stroke and a systematic review of time trends in other stroke incidence studies and of rates of premorbid anticoagulation. Methods- The proportion of incident strokes with associated AF was determined in the OXVASC (Oxford Vascular Study; 2002-2017) and in other prospective, population-based stroke incidence studies published before December 2017. Proportions were pooled by Mantel Haenszel methods, and the pooled percentage of cases with premorbid anticoagulation was determined. Analyses were stratified by the age of study population, mid-study year, country, and ethnicity. Results- Of 1928 patients with incident ischemic stroke in OXVASC, 629 (32.6%; 95% CI, 30.5-34.7) were AF associated, consistent with the pooled estimate from 4 smaller studies over the same study period (608/1948; 31.2%, 30.0-32.4; Phet=0.80). The pooled estimate from all studies reporting premorbid AF over 25 million person-years of observation (1960 onwards; 33 reports) was lower (18.6%, 16.8-20.3) and more heterogeneous (Phet<0.0001), but 62% of heterogeneity was explained by the age of study population, study period, country, and ethnicity. The proportion of incident strokes on premorbid anticoagulation increased over time, both for ischemic stroke in OXVASC (2002-2007: 15.1%, 2008-2012: 19.6%, and 2013-2017: 35.9%; Ptrend<0.0001), and across all studies (P=0.002), but the pooled estimates suggested substantial undertreatment even in the most recent periods (2001-2015: 25.7%, 21.1-30.3 and ≥2010: 31.6%, 18.2-44.9). Conclusions- About 1 in 3 incident ischemic strokes are still AF associated, due partly to low rates of anticoagulation for known prior AF, which therefore represents a major public health opportunity to reduce the burden of stroke.

Prediction of hemorrhagic transformation in patients with mild atrial fibrillation-associated stroke treated with early anticoagulation: post hoc analysis of the Triple AXEL Trial

ObjectivesTo investigate the predictors of hemorrhagic transformation (HT) in patients with mild atrial fibrillation-related stroke who were treated with early anticoagulation. We conducted a post-hoc subgroup analysis from Acute Cerebral Infarction Patients with Non-valvular Atrial Fibrillation (Triple AXEL) study. Patients and methodsThe Triple AXEL study was a randomized, multicenter, open-label, blinded end-point evaluation, comparative phase 2 trial. To identify the relationship between the type of HT and risk factors. We analyzed various factors using data from the Triple AXEL study, such as sex, history of hypertension, diabetes, microbleeds, concomitant antiplatelet use, initial infarction volume, initial infarction location, and new intracranial hemorrhage on follow-up gradient recalled echo or susceptibility-weighted imaging. ResultsWe analyzed various factors by dividing patients into a new HT group and a no HT group. No correlation was found between HT and risk factors that were significantly associated with HT, including age, sex, history of hypertension, diabetes, microbleeds, concomitant antiplatelet use, and initial infarction volume. When the initial infarction was classified into anterior circulation infarction (ACI) and posterior circulation infarction (PCI), the occurrence of new HT was significantly more associated with PCI than with ACI (57.6% vs 24.0%, P = 0.001). Multivariate logistic regression analysis was performed using HT as a response variable. Only the location of initial infarction according to the vascular territory contributed to the increased risk of HT (OR2.3, 95%CI1.33–3.91, P = 0.003). ConclusionPCI is a very important independent risk factor for HT in patients with mild AF-related stroke treated with early anticoagulation.

Clinical significance of acute and chronic ischaemic lesions in multiple cerebral vascular territories.

To investigate the association between acute and chronic ischaemic lesions in a multiple territory lesion pattern (MTLP) detected by 3-Tesla MRI and stroke aetiology, specifically atrial fibrillation-associated stroke. We analysed data from the 1000+ study - a prospective, observational 3-Tesla MRI cohort study of consecutively included acute stroke patients. Acute and chronic lesions were detected by DWI and fluid-attenuated inversion recovery, respectively. Observers blinded to clinical data allocated lesions to the right anterior, left anterior or posterior circulation. Lesion pattern was categorised as MTLPa/c when more than one territory was affected by either acute or chronic lesions or as MTLPa when more than one territory was affected by acute lesions alone. Of the 1,000 included patients, an MTLPa/c was found in 43% and MTLPa in 24%. Advanced age (aOR=1.21 per 10 years, 95% CI 1.06-1.39), atrial fibrillation (aOR=1.44, 95% CI 1.06-1.94), aortic arch atherosclerosis (aOR=2.52, 95% CI 1.10-5.77), malignant disease (aOR=1.99, 95% CI 1.25-3.16) and lower estimated glomerular filtration rate (eGFR) (aOR=0.90 per 10 ml, 95% CI 0.84-0.97) were associated with MTLPa/c. Only malignant disease (aOR=2.03, 95% CI 1.27-3.23) and lower eGFR (aOR=0.91 per 10 ml, 95% CI 0.85-0.97) were associated with MTLPa. An MRI-detected multiple territory lesion pattern of acute and chronic ischaemic lesions is frequent and more often present in older patients and patients with atrial fibrillation, aortic arch atherosclerosis, malignant disease and lower eGFR. Considering not only acute but also chronic ischaemic lesions may facilitate identifying atrial fibrillation-associated or aorto-embolic stroke. • Brain imaging with MRI may help to determine the aetiology of stroke. • Of 1,000 stroke patients undergoing 3-Tesla MRI, 43% had acute and chronic ischaemic lesions in multiple cerebral vascular territories. • Atrial fibrillation, aortic arch atherosclerosis and malignant disease were associated with a multiple territory lesion pattern.

111Therapeutic Anticoagulation: A Determinant of Outcome after Atrial Fibrillation-Associated Stroke

111Therapeutic Anticoagulation: A Determinant of Outcome after Atrial Fibrillation-Associated Stroke

Anticoagulation for stroke prevention in elderly patients with non-valvular atrial fibrillation: what are the obstacles?

The elderly with atrial fibrillation are more prone to stroke. Oral anticoagulants such as warfarin are effective in the prevention of atrial fibrillation-associated stroke and systemic embolism. The CHADS2 or CHA2D2-VASc score and HAS-BLED score were developed to stratify stroke risk associated with atrial fibrillation and bleeding risk in a patient with atrial fibrillation, respectively, to facilitate the decision for and safe use of oral anticoagulant. Nonetheless, the decision for anticoagulation is not straightforward and the elderly with non-valvular atrial fibrillation are often precluded from anticoagulant prescription. Advanced age and disadvantages associated with the elderly such as fall, comorbidities, cognitive impairment, and polypharmacy contribute to the over-concern of physicians about bleeding risk. Various treatment options such as low-intensity warfarin and aspirin plus clopidogrel have been suggested but are inferior to dose-adjusted warfarin. Novel oral anticoagulants with promising efficacy and convenience hold great appeal. Optimal management of underlying medical conditions and modifiable stroke risk factors, together with intervention to improve the safe use of oral anticoagulants, are useful.

Neurologist ambulatory care, health care utilization, and costs in a large commercial dataset.

To determine the value of neurologist ambulatory care in chronic neurologic diseases in a large administrative claims dataset detailing costs, adverse events, and health care utilization. The Optum proprietary claims dataset (2010-2012) was examined to describe direct health care costs, as well as specific outcome metrics for a large population of persons with chronic neurologic illnesses. In phase I of the study, we detail neurologist involvement and differences in annualized allowed third--party payments within episode treatment groups (ETGs) for 10 neurologic illnesses. For phase II, we examined health care utilization for ETGs of epilepsy, Parkinson disease (PD), stroke, and multiple sclerosis (MS) with and without neurologist involvement. Reported outcomes were unadjusted differences and odds ratios between treatment groups. For phase I, a total of 1,913,605 ETGs for 10 neurologic conditions were identified, 30.1% meeting criteria for neurologist involvement. All conditions had higher direct costs when neurologists were involved with care, ranging from a 25% increase for Alzheimer dementia to 100% more for MS care. In phase II, fractures, infections, emergent care, and inpatient admission were less with neurologist ambulatory care, while neurologist care was associated with greater utilization of disease-specific treatments (immunotherapies in MS anticoagulation in atrial fibrillation-associated stroke, deep brain stimulation and dopaminergic therapies in PD). Neurologist involvement with care is associated with greater unadjusted allowed payments, but fewer adverse events and less acute care utilization.

Is there a role for warfarin anymore?

Reduction of atrial fibrillation-associated stroke risk has become the leading indication for warfarin use. Optimal management of warfarin can only be achieved with a relatively complex infrastructure. Alternative anticoagulant agents have been developed, and 3 have demonstrated effectiveness, safety, and adherence that are comparable or superior to warfarin in the clinical trial setting. None of the novel agents requires routine laboratory testing to demonstrate effective anticoagulation. Whereas these new agents present potential advantages, such as fixed dosing and dramatically reduced intracranial hemorrhaging, they are also subject to caveats that ought to be considered in the context of an "ideal" anticoagulant. If used casually, they have the potential to worsen rather than improve health care outcomes. There is little question that the management burden of the novel agents will be less than with warfarin. However, with a hemorrhagic risk that was similar to warfarin in these trials, there will likely remain a significant need for both baseline education and some level of focused interval follow-up to assess for bleeding risk and adherence considerations. These novel agents offer a definite advance in the available management options for thromboembolic disease, but until we understand the requirements for safe and effective use in the routine clinical setting, we will not be able to establish the extent to which they should replace warfarin.

Abstract 171: A Population-based Comparison of Total Costs: The Economic Burden of Atrial Fibrillation-Associated Stroke

Introduction Accurate health economics data is essential for service planning and clinical guideline development. Stroke associated with atrial fibrillation (AF) is characteristically more severe and disabling than non-AF stroke. Few data exist on the economic impact of AF-stroke compared to non-AF-stroke in population-based samples. Methods The North Dublin Population Stroke Study is a population-based prospective study of incident stroke in Dublin, Ireland. Both direct (healthcare-related) and indirect costs were calculated over a 2-year post-stroke period for individual patients, using data for survival and disability, discharge destination, outpatient and family practitioner visits, community supports, and ongoing treatment. Acute inpatient care was costed using the casemix approach, measuring the resource use per hospitalization (index stroke plus post-stroke admissions). Length of stay was used to cost rehabilitation and nursing home admissions. Indirect costs of illness were calculated using in-hospital length of stay to determine loss of productivity. Total costs were compared for AF-stroke and non-AF stroke, calculated at 2007 prices and converted to US$ (2007 rates). Results Of 568 ischemic and hemorrhagic incident stroke patients, 31% (177) had AF-associated stroke. 2-year fatality was higher in AF-stroke patients (50.3% versus 35.1%, p=0.001). Total 2-year median cost was $34,982 for AF-stroke patients (25-75% IQR $14,213-$88,283) compared to median cost of $17,736 (25-75% IQR $10,803-45,838] in non-AF stroke patients (p&lt;0.001). Inpatient care contributed 47% of total costs: cost per AF-stroke patient (index stroke) was median $14,257 (IQR $10,286-$40,989) compared to median $10,624 per non-AF stroke patient (IQR $9,482-26,241, p=0.002). Long-term institutional care was the second highest cost contributor with greater proportions of living AF stroke patients in nursing homes (2-year mean cost $23,997(±standard deviation [SD] $68,585) versus non-AF-stroke (mean $12,988 (±SD $51,561, p=0.002 for cost comparison). Community supports (2-year mean $5,487 ±SD $13,283 versus $3,808 ±SD $11,844 (p=0.1), post-stroke specialized equipment (mean $2,729±$8,927 vs $2,122±$8,267, p=0.2), and repeat hospital admission (mean $3,580±$12,124 vs $1,951±$8,446, p=0.4) costs were non-significantly higher in patients with AF-stroke. In linear regression models, AF was an independent predictor of total costs after adjusting for age (p=0.02, β 0.1) but the association was lost on adding stroke severity (72-hour Rankin score) (p=0.1, β 0.07). Conclusion In this population study, AF-associated stroke was associated with substantially higher costs for hospitalisation and community support after discharge. With ageing populations and increasing stroke burden, AF-stroke is likely to account for an increasing proportion of overall cost to health services.

Advanced Age, Anticoagulation Intensity, and Risk for Intracranial Hemorrhage among Patients Taking Warfarin for Atrial Fibrillation

The risk for atrial fibrillation-associated stroke increases at low anticoagulation intensities. However, higher intensities increase hemorrhage risk. Optimal use of warfarin for atrial fibrillation requires precise information on the risk for intracranial hemorrhage as a function of patient age and anticoagulation intensity. To examine the relationship of age, anticoagulation intensity, and risk for intracranial hemorrhage. Case-control study. Academic medical center. 170 case-patients who developed intracranial hemorrhage during warfarin therapy and 1020 matched controls who did not; both case-patients and controls were taking warfarin for atrial fibrillation. The authors performed multivariable conditional logistic regression to determine the odds of intracranial hemorrhage with regard to age and international normalized ratio (INR), controlling for comorbid conditions and aspirin use. Case-patients were older than controls (median age, 78 years vs. 75 years; P < 0.001) and had higher median INRs (2.7 vs. 2.3; P < 0.001). The risk for intracranial hemorrhage increased at 85 years of age or older (adjusted odds ratio, 2.5 [95% CI, 1.3 to 4.7]; referent age, 70 to 74 years) and at an INR range of 3.5 to 3.9 (adjusted odds ratio, 4.6 [CI, 2.3 to 9.4]; referent INR, 2.0 to 3.0). The risk for intracranial hemorrhage at INRs less than 2.0 did not differ statistically from the risk at INRs of 2.0 to 3.0 (adjusted odds ratio, 1.3 [CI, 0.8 to 2.2]). Although duration of anticoagulation has been associated with hemorrhage in other studies, the current study could not control for this potential confounder. The risk for intracranial hemorrhage increases at age 85 years. International normalized ratios less than 2.0 were not associated with lower risk for intracranial hemorrhage compared with INRs between 2.0 and 3.0. Therefore, anticoagulation management should focus on maintaining INRs in the 2.0 to 3.0 range, even in elderly patients with atrial fibrillation, rather than targeting INRs less than 2.0. Similarly, INRs of 3.5 or greater should be avoided.

Antithrombotic therapies for stroke prevention.

Aspirin is the most widely used antiplatelet agent, reducing nonfatal ischemic stroke by 22%. There is increasing evidence that the efficacy of aspirin may vary with the etiologic subtype of stroke. Although the cost and side effects have limited the use of ticlopidine, patients who are intolerant of aspirin and those experiencing transient ischemic attack or stroke during aspirin therapy should be given ticlopidine. Patients with atrial fibrillation have a five-fold increased risk of stroke and require prophylactic therapy with warfarin or aspirin. Aspirin is less effective than warfarin in preventing atrial fibrillation-associated stroke, but the higher risk of hemorrhagic complications and frequent monitoring associated with warfarin must be considered. Clinical and echocardiographic predictors of increased thromboembolic risk in atrial fibrillation patients have been identified and may direct the treatment choice.