Mainstay Of Stroke Prevention Research Articles

Minimally invasive left atrial appendage occlusion plus reduced dose direct oral anticoagulant to prevent stroke in patients with atrial fibrillation-the LAAO-PlusRE.

The onset of atrial fibrillation (AF) has a direct association with left atrial appendage (LAA) function, as demonstrated by recent studies demonstrating the link between left atrial (LA) wall fibrosis, impaired contractility, and the development of AF. Non-valvular AF (NVAF) affects almost 30 million people worldwide, with this number expected to increase in the next 20 years. It is the main cause of ischemic stroke, with significant subsequent economic and social impact. Currently, the mainstay of stroke prevention in patients with NVAF is oral anticoagulation (OAC), which reduces the incidence of ischemic events at the stake of increased hemorrhagic events. Despite the introduction and widespread use of direct oral anticoagulants (DOACs), which almost completely replaced vitamin K antagonists (VKAs), the adherence to OAC is still low, hindering the efficacy of stroke prevention. Percutaneous LAA occlusion (LAAO) is now indicated (class IIB) in patients with NVAF at increased ischemic risk who cannot undergo OAC. Recently published data demonstrated that a reduced dose of DOAC after percutaneous LAAO is superior to long-term dual antiplatelet therapy (DAPT) for stroke prevention in the mid-term. One of the possible pitfalls of percutaneous LAAO is postprocedural peri-device leaks (PDLs) that have been associated with increased thromboembolic events. According to LAAOS III results, surgical LAAO during cardiac surgery brings a 33% reduction in risk of stroke at five years, independently from the OAC regimen with a high rate of complete appendage occlusion. The combination of surgical LAAO and reduced dose DOAC might ensure adequate embolic prevention, lowering the hemorrhagic risk. The present manuscript aims to describe the rationale and design of the Minimally Invasive Left Atrial Appendage Occlusion Plus REduced Dose DOAC To Prevent Stroke In Patients With Atrial Fibrillation Randomized Clinical Trial (LAAO-PlusRE).

Anticoagulants for atrial fibrillation: from warfarin and DOACs to the promise of factor XI inhibitors.

Anticoagulation is the mainstay of stroke prevention in appropriate patients with atrial fibrillation. Due to advances in pharmacotherapy the anticoagulants used for this purpose have evolved significantly over the past decades with the aim of optimizing effectiveness while minimizing bleeding risks. Though significant improvements have been made toward this goal, bleeding risk remains the major concern with these therapies. An investigational class of agents which inhibit Factor XI have shown promise in pre-clinical and early clinical trials to significantly minimize bleeding while maintaining efficacy against stroke and systemic embolism. This mini-review will discuss anticoagulants currently used for stroke prevention in patients with atrial fibrillation including warfarin and direct oral anticoagulants. We will also review the mechanism of action and data from early clinical trials for Factor XI inhibitors and discuss their potential advantages and shortcomings.

Cardiac and renal outcomes of direct oral anticoagulants in patients with atrial fibrillation.

Oral anticoagulation therapy with warfarin or direct oral anticoagulants (DOACs) is the mainstay for stroke prevention in patients with non-valvular atrial fibrillation (AF). The DOACs might have a lower risk of declining renal function than warfarin. This study aimed to compare renal outcomes among rivaroxaban, edoxaban, dabigatran, and warfarin. This cohort study identified 2203 adults with AF who started anticoagulation therapy between 1 July 2013 and 31 December 2020, in a clinical database at a single centre. Inverse probability of treatment weighting was adopted to balance baseline characteristics among four anticoagulants treatment groups. The primary outcome was a composite of cardiac and renal outcomes, involving a ≥30% decline in estimated glomerular filtration rate (eGFR), renal failure and cardiovascular death. After propensity score weighting, dabigatran was associated with significantly lower risks of a ≥30% decline in eGFR (hazard ratio [HR]: .69, 95% confidence interval [CI]: .497-.951, p = .0237), doubling of the serum creatinine level (HR: .49, 95% CI: .259-.927, p = .0282) and the cardiac and renal outcome composite (HR: .67, 95% CI: .485-.913, p = .0115) than warfarin. Rivaroxaban and edoxaban did not show significant protective effects on renal outcomes compared to warfarin. In this study, patients treated with dabigatran had significantly reduced risks of declining renal function and composite cardiac and renal events than those treated with warfarin. However, rivaroxaban and edoxaban were not associated with lower risks of any renal outcomes than warfarin. More studies are warranted to investigate and compare the impact of renal function between different DOACs in patients with AF.

Temporal changes in anticoagulant prescribing and atrial fibrillation: results of interrupted time-series analysis of openly available routine data in England

Abstract Introduction The use of anticoagulants for stroke prevention in patients with atrial fibrillation (AF) has been increasing in England in the recent years (1, 2). The changes in practice coincided with several developments in the area of anticoagulants and AF, including: the emergence of evidence supporting anticoagulant use for stroke prevention in AF, changes in guideline recommendations, and the licensing of direct oral anticoagulants (DOACs) as an alternative to warfarin, which was the mainstay of stroke prevention in AF. Currently, there are four DOACs available for use: dabigatran, rivaroxaban, apixaban, and edoxaban. Recent analyses of time trends of anticoagulant prescribing in England showed an increase in DOACs prescribing and a decrease in warfarin prescribing (1, 2). However, more recent exploration of recent anticoagulant prescribing trends is needed. Aim To explore the changes in anticoagulant prescribing for AF in England. Methods Interrupted time-series analysis (ITSA) of openly available data on anticoagulant prescribing and AF. Separate analyses were conducted for data from Sentinel Stroke National Audit Programme (SSNAP) and Quality and Outcomes Framework (QOF). The timeframe of the analysis and the length of time intervals depended on the characteristics of each dataset. Results Analysis of data from SSNAP showed that the proportion of stroke patients who have a diagnosis of AF who were taking an anticoagulant alone prior to admission increased from 32.51% in the third quarter of 2013 to 62.63% in the third quarter of 2020; this coincided with a decreased proportion of stroke patients who have a diagnosis of AF taking antiplatelets alone from 37.10% to 8.31% during the same period. Analysed QOF data on anticoagulants and AF included information about AF prevalence in QOF datasets, the eligibility of patients with AF for anticoagulant based on stroke risk assessment, and the use of anticoagulants among eligible patients. Prevalence of AF in England in QOF datasets increased from 1.52% in 2012/2013 to 2.05% in 2019/2020 (ITSA gradient=0.08, p-value<.001, 95% confidence interval: 0.07- 0.09). The proportion of patients with AF who are considered eligible for anticoagulation per all patients with AF in QOF datasets increased from 44.95% in 2012/2013 to 80.87% in 2019/2020; there was an increase by 25.24% between 2014/2015 and 2015/2016 which corresponds to modifying risk assessment scores to include additional criteria. The proportion of eligible patients with AF being prescribed anticoagulants also increased in the period between 2012/2013 and 2019/2020 (ITSA gradient = 1.98, p-value<.001, 95% confidence interval: 1.52- 2.44). Conclusion The analysis of data from different sources identified an increase in anticoagulant prescribing for patients with AF in England, which is likely to translate into health gains. However, the use of aggregate data in the analysis did not allow for detailed inspection of patient characteristics, and individual anticoagulants were not specified in the datasets. Therefore, quantitative analyses of primary care data of individual anticoagulant prescribing for different patient groups with AF are needed to further understand whether additional improvements are possible in the prevention of complications from atrial fibrillation. References (1) Adderley NJ, Ryan R, Nirantharakumar K, Marshall T. Prevalence and treatment of atrial fibrillation in UK general practice from 2000 to 2016. Heart. 2019;105(1):27-33. (2) Loo SY, Dell’Aniello S, Huiart L, Renoux C. Trends in the prescription of novel oral anticoagulants in UK primary care. British Journal of Clinical Pharmacology. 2017;83(9):2096-106.

Geriatric Conditions Are Associated With Decreased Anticoagulation Use in Long-Term Care Residents With Atrial Fibrillation.

BackgroundAnticoagulation is the mainstay for stroke prevention in patients with atrial fibrillation, but concerns about bleeding inhibit its use in residents of long‐term care facilities. Risk‐profiling algorithms using comorbid disease information (eg, CHADS2 and ATRIA [Anticoagulation and Risk Factors in Atrial Fibrillation]) have been available for years. In the long‐term care setting, however, providers and residents may place more value on geriatric conditions such as mobility impairment, activities of daily living dependency, cognitive impairment, low body mass index, weight loss, and fall history.Methods and ResultsUsing a retrospective cohort design, we measured the association between geriatric conditions and anticoagulation use and type. After merging nursing home assessments containing information about geriatric conditions (Minimum Data Set 2015) with Medicare Part A 2014 to 2015 claims and prescription claims (Medicare Part D) 2015 to 2016, we identified 228 741 residents with atrial fibrillation and elevated stroke risk (CHA2DS2‐VASc score ≥2) for our main analysis. Recent fall, activities of daily living dependency, moderate and severe cognitive impairment, low body mass index, and unintentional weight loss were all associated with lower anticoagulation use even after adjustment for multiple predictors of stroke and bleeding (odds ratios ranging from 0.51 to 0.91). Residents with recent fall, low body mass index, and unintentional weight loss were more likely to be using a direct oral anticoagulant, although the magnitude of this effect was smaller.ConclusionsGeriatric conditions were associated with lower anticoagulation use. Preventing stroke in these residents with potential for further physical and cognitive impairment would appear to be of paramount significance, although the net benefit of anticoagulation in these individuals warrants further research.

SUPPORT-AF IV: Supporting use of AC through provider prompting about oral anticoagulation therapy for AF clinical trial study protocol

BackgroundSix million Americans suffer from atrial fibrillation (AF), a heart rhythm abnormality that significantly increases the risk of stroke. AF is responsible for 15% of ischemic strokes, which lead to permanent disability in 60% of cases and death in up to 20%. Anticoagulation (AC) is the mainstay for stroke prevention in patients with AF. Despite guidelines recommending AC for patients, up to half of eligible patients are not on AC. Clinical decision support tools in the electronic health record (EHR) can help bridge the disparity in AC prescription for patients with AF.ObjectiveTo enhance and assess the effectiveness of our previous rule-based alert on AC initiation and persistence in a diverse patient population from UMass-Memorial Medical Center and University of Florida at Jacksonville.Methods/ResultsUsing the EHR, we will track AC initiation and persistence. We will interview both patients and providers to determine a measure of satisfaction with AC management. We will track digital crumbs to better understand the alert’s mechanism of effect and further add enhancements. These enhancements will be used to refine the alert and aid in developing an implementation toolkit to facilitate use of the alert at other health systems.ConclusionIf the number of AC starts, the likelihood of persisting on AC, and the frequency alert use are found to be higher among intervention vs control providers, we believe such findings will confirm our hypothesis on the effectiveness of our alert.

Current Evidence for the Use of Aspirin in Patients with Atrial Fibrillation and a CHA2DS2-Vasc=1

Aspirin was once the mainstay of stroke prevention in patients with atrial fibrillation. Its popularity was based on the results of the SPAF and PATAF trials, which showed the low risks of this therapy and the many benefits it had to offer in terms of embolic complications prevention. Nevertheless, aspirin has lost popularity in atrial fibrillation since the CHADS, CHA2DS2-VASc and HASBLED scoring systems were first introduced. These scoring systems showed a different perspective, which highlighted that thromboembolic risk varied among individuals and that a generalization on antiplatelet therapy for atrial fibrillation was not effective. These caveats gave support to additional treatments based on anticoagulation, including warfarin and direct oral anticoagulants. These treatments gained popularity based on the superiority over warfarin, first described on the BAFTA trial, which nominated the warfarin as the standard of care for atrial fibrillation thromboembolic prevention. Since then, direct anticoagulation therapies have gained popularity based on the results of the ARISTOTLE (apixaban), RE-LY (dabigatran), ROCKET-AF (rivaroxaban), ENGAGE TIMI 48 AF (edoxaban) trials. However, the CHA2DS2-VASc score was generous with aspirin, since it opened a possible recommendation for low CHA2DS2-VASc scores (0-1). This comprehensive literature review is intended to discuss the arguments behind this last statement and to show the available evidence in favor of and against aspirin for non-valvular atrial fibrillation in low thromboembolic risk patients.

Red cell exchange transfusions lower cerebral blood flow and oxygen extraction fraction in pediatric sickle cell anemia

AbstractBlood transfusions are the mainstay of stroke prevention in pediatric sickle cell anemia (SCA), but the physiology conferring this benefit is unclear. Cerebral blood flow (CBF) and oxygen extraction fraction (OEF) are elevated in SCA, likely compensating for reduced arterial oxygen content (CaO2). We hypothesized that exchange transfusions would decrease CBF and OEF by increasing CaO2, thereby relieving cerebral oxygen metabolic stress. Twenty-one children with SCA receiving chronic transfusion therapy (CTT) underwent magnetic resonance imaging before and after exchange transfusions. Arterial spin labeling and asymmetric spin echo sequences measured CBF and OEF, respectively, which were compared pre- and posttransfusion. Volumes of tissue with OEF above successive thresholds (36%, 38%, and 40%), as a metric of regional metabolic stress, were compared pre- and posttransfusion. Transfusions increased hemoglobin (Hb; from 9.1 to 10.3 g/dL; P < .001) and decreased Hb S (from 39.7% to 24.3%; P < .001). Transfusions reduced CBF (from 88 to 82.4 mL/100 g per minute; P = .004) and OEF (from 34.4% to 31.2%; P < .001). At all thresholds, transfusions reduced the volume of peak OEF found in the deep white matter, a location at high infarct risk in SCA (P < .001). Reduction of elevated CBF and OEF, both globally and regionally, suggests that CTT mitigates infarct risk in pediatric SCA by relieving cerebral metabolic stress at patient- and tissue-specific levels.

Comparison of bleeding risk scores in patients with atrial fibrillation: insights from the RE-LY trial.

Oral anticoagulation is the mainstay of stroke prevention in atrial fibrillation (AF), but must be balanced against the associated bleeding risk. Several risk scores have been proposed for prediction of bleeding events in patients with AF. To compare the performance of contemporary clinical bleeding risk scores in 18113 patients with AF randomized to dabigatran 110mg, 150mg or warfarin in the RE-LY trial. HAS-BLED, ORBIT, ATRIA and HEMORR2 HAGES bleeding risk scores were calculated based on clinical information at baseline. All major bleeding events were centrally adjudicated. There were 1182 (6.5%) major bleeding events during a median follow-up of 2.0years. For all the four schemes, high-risk subgroups had higher risk of major bleeding (all P<0.001). The ORBIT score showed the best discrimination with c-indices of 0.66, 0.66 and 0.62, respectively, for major, life-threatening and intracranial bleeding, which were significantly better than for the HAS-BLED score (difference in c-indices: 0.050, 0.053 and 0.048, respectively, all P<0.05). The ORBIT score also showed the best calibration compared with previous data. Significant treatment interactions between the bleeding scores and the risk of major bleeding with dabigatran 150mg BD versus warfarin were found for the ORBIT (P=0.0019), ATRIA (P<0.001) and HEMORR2 HAGES (P<0.001) scores. HAS-BLED score showed a nonsignificant trend for interaction (P=0.0607). Amongst the current clinical bleeding risk scores, the ORBIT score demonstrated the best discrimination and calibration. All the scores demonstrated, to a variable extent, an interaction with bleeding risk associated with dabigatran or warfarin.

Approaches to Left Atrial Appendage Closure: Device Design, Performance, and Limitations.

Up to 6.1 million people in the United States have atrial fibrillation (AF), which is associated with an increased risk of stroke. Oral anticoagulants are the mainstay of stroke prevention in AF. For decades, warfarin was the only available drug, fraught with compliance limitations, a narrow therapeutic window, and a high risk of hemorrhage. Pharmacologic developments have produced new anticoagulants that have improved the rates of stroke related to AF; however, they still confer a high risk of bleeding, making them unsuitable for some patients. Studies have shown that roughly 90% of strokes in patients with AF occur in the left atrial appendage (LAA). This understanding has prompted the development and testing of novel percutaneous strategies for LAA closure as an alternative to anticoagulation therapy. The following review examines the relative merits and shortcomings of these strategies and explores future prospects in the prevention of AF-related stroke.

Large Artery Atherosclerotic Occlusive Disease

Extracranial or intracranial large artery atherosclerosis is often identified as a potential etiologic cause for ischemic stroke and transient ischemic attack. Given the high prevalence of large artery atherosclerosis in the general population, determining whether an identified atherosclerotic lesion is truly the cause of a patient's symptomatology can be difficult. In all cases, optimally treating each patient to minimize future stroke risk is paramount. Extracranial or intracranial large artery atherosclerosis can be broadly compartmentalized into four distinct clinical scenarios based upon the individual patient's history, examination, and anatomic imaging findings: asymptomatic and symptomatic extracranial carotid stenosis, intracranial atherosclerosis, and extracranial vertebral artery atherosclerotic disease. This review provides a framework for clinicians evaluating and treating such patients. Intensive medical therapy achieves low rates of stroke and death in asymptomatic carotid stenosis. Evidence indicates that patients with severe symptomatic carotid stenosis should undergo carotid revascularization sooner rather than later and that the risk of stroke or death is lower using carotid endarterectomy than with carotid stenting. Specific to stenting, the risk of stroke or death is greatest among older patients and women. Continuous vascular risk factor optimization via sustained behavioral modifications and intensive medical therapy is the mainstay for stroke prevention in the setting of intracranial and vertebral artery origin atherosclerosis. Lifelong vascular risk factor optimization via sustained behavioral modifications and intensive medical therapy are the key elements to reduce future stroke risk in the setting of large artery atherosclerosis. When considering a revascularization procedure for carotid stenosis, patient demographics, comorbidities, and the periprocedural risks of stroke and death should be carefully considered.

Abstract 35: Transfusion Relieves Cerebral Metabolic Stress in Children with Sickle Cell Disease

Introduction: Transfusions (Tx) are the mainstay of stroke prevention in children with sickle cell disease (SCD), but the pathophysiology conferring this neuroprotection is not well understood. Hypothesis: Tx relieves cerebral metabolic stress by improving arterial oxygen content, thereby lowering chronically-elevated cerebral blood flow (CBF) and oxygen extraction fraction (OEF) in children with SCD at risk for stroke. Methods: Children with SCD on chronic Tx therapy underwent two brain MRIs with measurement of CBF via pseudocontinuuous arterial spin labeling and OEF via asymmetric spin echo sequence within 24 hours of exchange Tx. To determine how Tx may reduce regions of elevated OEF, we set absolute OEF thresholds (45, 47.5, 50%) and compared tissue volumes above each threshold pre- and post-Tx using nonparametric paired statistics. Results: Twelve children with SCD (6-21 yrs) underwent MRIs. Tx raised Hb and lowered CBF and OEF (Figure), suggesting that elevated CBF and OEF may be markers of metabolic stress relieved by Tx. While CBF correlates with age in healthy children, pre-Tx CBF correlation with age was lost (τ= -0.42, p=0.07), but regained post-Tx (τ= -0.76, p=0.001). Also, absolute change in OEF diminished with increasing age (τ=. -0.75, p=0.003). Regions with very high OEF were found in the periventricular white matter, a common area of infarcts in SCD (Figure, average OEF maps pre- and post-Tx). Tx reduced the volume of these brain regions defined by all three OEF thresholds (Table), suggesting that Tx reduces brain regions at high risk for stroke. Conclusion: Tx in SCD children improves arterial oxygen content by increasing Hb, allowing CBF and OEF to fall, thus relieving metabolic stress globally and regionally. The absolute change in OEF correlates with age, suggesting that the efficacy of Tx may be age-dependent.

Direct Oral Anticoagulants for the Prevention of Stroke in Patients with Nonvalvular Atrial Fibrillation: Understanding Differences and Similarities.

The presence of atrial fibrillation (AF), the most common sustained cardiac arrhythmia, significantly increases the risk for stroke. Current guidelines recommend that the vitamin K antagonist warfarin or direct oral anticoagulants (DOACs), such as the approved direct thrombin inhibitor dabigatran and the approved direct factor Xa inhibitors apixaban, rivaroxaban, and edoxaban, should be used for thromboprophylaxis in patients with nonvalvular AF at risk for stroke or systemic embolic events (SEE). Warfarin, the mainstay of stroke prevention in AF, increases the risk of major bleeding. Furthermore, warfarin therapy comes with several limitations including frequent monitoring and the need for dose adjustments, unpredictable pharmacokinetics and pharmacodynamics, and the potential for significant drug-drug and food-drug interactions. The DOACs were developed to overcome these limitations while maintaining or surpassing warfarin’s efficacy and safety profiles. All four DOACs have similar or better efficacy and safety compared with warfarin and are therefore valuable alternatives for the prevention of stroke and SEE in patients with nonvalvular AF. Understanding the subtle differences in the DOACs’ pharmacology, phase 3 study designs, and trial outcomes will allow for a more tailored approach in selecting the right oral anticoagulant for each patient.

Percutaneous left atrial appendage closure: a review of the WATCHMAN clinical trial experience

The burden of atrial fibrillation (AF) and associated risk of stroke continues to grow with an aging population. The mainstay of stroke prevention in AF is oral anticoagulation. However, a large number of patients cannot, or choose not to take oral anticoagulation due to associated bleeding. Left atrial appendage (LAA) closure is an alternative strategy of stroke prevention in the setting of AF for patients with reasons to avoid chronic oral anticoagulants. The most rigorously studied means of LAA closure is the WATCHMAN device. The WATCHMAN device is a nitinol framed intracardiac device, placed in the LAA via a transseptal approach. We review the option of WATCHMAN LAA closure including the evidence behind its use and future directions for LAA closure research.

Apixaban versus edoxaban for stroke prevention in nonvalvular atrial fibrillation.

Oral anticoagulation therapy is the mainstay of stroke prevention in nonvalvular atrial fibrillation patients. Vitamin K antagonists (such as warfarin) have been effective conventional oral anticoagulants for several decades. However, due to their limitations in clinical use, several nonvitamin K antagonist oral anticoagulants (NOACs, including dabigatran, rivaroxaban, apixaban and edoxaban) have been developed. Nonetheless, no head to head trials have been performed to directly compare these NOACs in patient cohorts. In this review article, two direct factor Xa inhibitors, apixaban and edoxaban, are briefly described with focus on their pharmacokinetic and pharmacodynamic profiles, plus drug interactions. Moreover, both efficacy and safety will be discussed based on the available data from the large Phase III clinical trials and indirect comparison studies.

Rivaroxaban in the Prevention of Stroke and Systemic Embolism in Patients with Non-Valvular Atrial Fibrillation: Clinical Implications of the ROCKET AF Trial and Its Subanalyses.

Atrial fibrillation (AF) is an increasingly common cause of stroke and systemic embolism. While warfarin has been the mainstay of stroke prevention in patients with AF, newer novel oral anticoagulant medications are now available. Rivaroxaban, a direct factor Xa inhibitor with a rapid onset and offset after oral administration, offers potential advantages over warfarin, predominantly due to its predictable pharmacokinetics across wide patient populations. It requires no coagulation monitoring, and only two different doses are needed (20mg daily for patients with normal renal function and 15mg daily in those with reduced renal function). A large randomized trial (ROCKET AF) has shown non-inferiority to warfarin for preventing stroke or systemic embolism in the per-protocol population and superiority to warfarin in the on-treatment safety population. Several subanalyses confirm that the treatment effect of rivaroxaban is consistent across different patient subgroups, including those with reduced renal function. The tolerability of rivaroxaban appears similar to that of warfarin, with comparable overall bleeding rates in clinical trials. In ROCKET AF, significantly lower rates of fatal and intracranial bleeding were seen with rivaroxaban, while lower rates of gastrointestinal bleeding were seen with warfarin. Important contraindications to rivaroxaban include valvular AF, the presence of a prosthetic valve (mechanical or bioprosthetic) or valve repair, the need for concurrent dual antiplatelet therapy, and creatinine clearance <30ml/min. Once-daily dosing and the lack of coagulation monitoring may increase utilization and adherence compared with warfarin, potentially decreasing the large burden of care associated with stroke secondary to AF. Overall, rivaroxaban offers a useful alternative to warfarin for stroke prevention in patients with AF.

Moving Beyond Warfarin—Are We Ready?: A Review of the Efficacy and Safety of Novel Anticoagulant Agents Compared to Warfarin for the Management of Atrial Fibrillation in Older Adults

Atrial fibrillation (AF) is one of the most common cardiac arrhythmias seen in clinical practice. Stroke risk in patients diagnosed with AF increases from 1.5% in the fifth decade of life to 23.5% in patients older than 80, emphasizing the need for effective and appropriate therapies. Over the past 50 years, vitamin K antagonists-namely warfarin (Coumadin(®))-have been the mainstay for stroke prevention. The introduction of dabigatran (Pradaxa(®)), rivaroxaban (Xarelto(®)), and apixaban (Eliquis(®)) has caused both patients and providers to question whether better alternatives to warfarin therapy exist. These agents have shown to be at least as effective as warfarin in stroke risk reduction with no need for international normalized ratio monitoring. This review will examine these newer anticoagulant agents' safety and efficacy and provide clinical considerations for treating older adults with AF. Clinicians with patients unable to tolerate warfarin or with difficulty managing therapy will need to consider patient characteristics, cost, adherence, lack of a reversal agent, and long-term efficacy before prescribing these agents.

Review of Challenges in Optimizing Oral Anticoagulation Therapy for Stroke Prevention in Atrial Fibrillation

Oral anticoagulant therapy is the mainstay of stroke prevention in patients with atrial fibrillation; it is highly effective at reducing stroke risk, but its use can be limited by increased risk of bleeding. As new oral anticoagulants are available, barriers to optimal use of oral anticoagulation therapy warrant consideration by healthcare professionals and administrators who are seeking to optimize the quality of care for patients with atrial fibrillation. Suboptimal use of oral anticoagulation therapy constitutes an important health problem with significant humanistic and economic consequences. Based on a review of the medical literature published between 2000 and 2011, this article summarizes the literature on the barriers to optimal use of oral anticoagulation therapy, describes the clinical and economic burdens that these barriers add to the burden of atrial fibrillation, and discusses how well the new oral anticoagulants may address some of these issues.

Sneddon's syndrome

The risk of recurrence of stroke in patients with systemic lupus erythematosus (SLE) is much higher than in other stroke patients, and the preventative treatment is influenced by the underlying systemic disease. Microinfarcts and microhemorrhages are seen frequently in autopsy specimens of SLE patients. Asymptomatic microinfarcts are common, and are now diagnosed due to the high sensitivity of MRI. Occlusions of large arteries and major strokes also occur in lupus patients. Atherosclerosis may be more frequent in SLE patients than in the general population. The major causes of stroke in lupus are cardiogenic emboli and hypercoagulable (including hypofibrinolytic) states, and the mainstay of stroke prevention is long-term warfarin, with an international normalized ratio (INR) of approximately 3.0. Although stroke is an important problem in lupus patients, leading to significant morbidity in young patients, SLE is relatively uncommon in young patients presenting with strokes or transient ischemic attacks (TIAs).

Lessons from the Stroke Prevention in Atrial Fibrillation trials.

Atrial fibrillation predisposes to left atrial thrombus formation and carries a sixfold increased risk for stroke. Antithrombotic therapies are the mainstay for stroke prevention. The National Institute of Neurological Disorders and Stroke-sponsored Stroke Prevention in Atrial Fibrillation (SPAF) studies assessed the value of warfarin, aspirin, and their combination for preventing stroke in six multicenter trials involving 3950 participants. This review presents the major results and implications, which offer unique perspectives on antithrombotic therapies for stroke prevention in atrial fibrillation. Warfarin and aspirin reduce stroke. Anticoagulation substantially benefits high-risk patients with atrial fibrillation, while many younger patients with atrial fibrillation have a low stroke rate when given aspirin. Pathogenetic and transesophageal echocardiographic correlations shed light on mechanisms by which antithrombotic agents prevent stroke. Warfarin inhibits formation of atrial appendage thrombi and markedly reduces cardioembolic strokes, while aspirin primarily prevents smaller, noncardioembolic strokes. The SPAF III stroke risk stratification scheme has been validated for identifying patients with high versus moderate versus low risk for stroke. Women with atrial fibrillation benefit from anticoagulation significantly more than men do. Many elderly patients with recurrent paroxysmal atrial fibrillation have high rates of stroke. Antithrombotic prophylaxis should be individualized on the basis of the estimated risk for stroke during aspirin therapy and the risk for bleeding during anticoagulation. Overall, nearly one third of patients with atrial fibrillation are low risk and should be treated with aspirin, and about one third are high risk and should receive warfarin if it can be given safely. For patients at moderate risk for stroke, patient preferences and access to reliable anticoagulation monitoring are particularly relevant.