Ischemic Stroke Atrial Fibrillation Research Articles

Impact of standardized MONitoring for Detection of Atrial Fibrillation in Ischemic Stroke (MonDAFIS): Rationale and design of a prospective randomized multicenter study

Atrial fibrillation (AF) is estimated to account for approximately every fifth ischemic stroke. In routine clinical practice, detection of undiagnosed, clinically silent AF represents a major diagnostic challenge, and in up to 30% of patients with ischemic stroke, AF remains undetected. The MonDAFIS study has been designed to quantify the diagnostic yield and clinical relevance of systematic electrocardiogram (ECG) monitoring for patients with acute ischemic stroke during the subsequent in hospital stay. A prospective randomized multicenter study in 3,470 patients with acute ischemic stroke or transient ischemic attack and without known AF on hospital admission. Over a period of approximately 2years, patients will be enrolled in about 30 German-certified stroke units and randomized 1:1 to receive either usual stroke unit diagnostic procedures for detection of AF (control group) or usual stroke unit diagnostic procedures plus standardized and centrally analyzed Holter ECG recording for up to 7days in hospital (intervention group). Results of the ECG core laboratory analysis will be provided to the patients and treating physicians. All patients will be followed up for treatment and cardiovascular outcomes at 6, 12, and 24months after enrollment. The primary outcome of the randomized MonDAFIS study is the proportion of patients who receive anticoagulation therapy 12months after the index stroke. Secondary outcomes include the number of stroke patients with newly detected AF in hospital and the rate of recurrent stroke, major bleedings, myocardial infarction, or death 6, 12, and 24months after the index event. MonDAFIS will also explore patient-reported adherence to anticoagulants, the clinical relevance of short atrial tachycardia, or excessive supraventricular ectopic activity as well as cost-effectiveness of prolonged, centrally analyzed ECG recordings. MonDAFIS will be the largest study to date to evaluate whether a prolonged and systematic ECG monitoring during the initial in hospital stay has an impact on secondary stroke prevention. In addition, prognosis as well as adherence to medication up to 2 years after the index stroke will be analyzed. The primary results of the MonDAFIS study may have the potential to change the current guidelines recommendations regarding ECG workup after ischemic stroke.

Inadequate anticoagulation by Vitamin K Antagonists is associated with Major Adverse Cardiovascular Events in patients with atrial fibrillation

BackgroundTime in therapeutic range (TTR) reflects the quality of anticoagulation and is inversely correlated with ischemic stroke in atrial fibrillation (AF) patients. Few data on the relationship between TTR and myocardial infarction (MI) are available. We investigated the association between TTR and Major Adverse Cardiovascular Events (MACE) in a cohort of anticoagulated AF patients. MethodsWe calculated TTR for 627 AF patients on vitamin K antagonists, who were followed for a median of 30.8months (1755patients/year). The primary outcome was a combined endpoint of MACE including fatal/nonfatal MI and cardiovascular death. ResultsMean age was 73.3 (±8.2) years, and 40.2% were women. During follow-up, we recorded 67 events: 19 stroke/TIA (1.1%/year) and 48 MACE (2.9%/year): 24 MI and 24 cardiovascular deaths. The cohort was categorized according to tertiles of TTR values: TTR 13–58%, 59–74%, and 75–100%. There was a significant increased rate of MACE across tertiles of TTR (Log-Rank test: p<0.001). On Cox proportion hazard analysis, the 2nd vs. 1st tertile of TTR (p=0.002, hazard ratio [HR] 0.347, confidence interval [CI] 95% 0.177–0.680), 3rd vs. 1st tertile of TTR (p<0.001, HR 0.164, CI 95% 0.067–0.402), age (p<0.001, HR 1.094, CI 95% 1.042–1.148), history of stroke/TIA (p=0.015, HR 2.294, CI 95% 1.172–4.490) and smoking (p=0.003, HR 3.450, CI 95% 1.532–7.769) predicted MACE. ConclusionTTR was an independent predictor of MACE in our cohort of AF patients. Our findings suggest that a good anticoagulation control is necessary to reduce not only the risk of stroke but also that of MACE.

Impact of standardized MONitoring for Detection of Atrial Fibrillation in Ischemic Stroke

Impact of standardized MONitoring for Detection of Atrial Fibrillation in Ischemic Stroke

Abstract 179: Ischemic Stroke in Atrial Fibrillation: 30-day Outcomes and Factors Associated with Severity

Background and Hypothesis: Ischemic stroke (IS) in atrial fibrillation (AF) is associated with high mortality. Inflammation, endothelial dysfunction, and hypercoagulability, in addition to blood stasis in the left atrium, play a critical role in thrombogenesis in AF. Hyperglycemia and chronic kidney disease (CKD) are potent triggers for inflammation, oxidative stress, and thrombogenesis. Statins have been shown to possess anti-inflammatory, anti-oxidant, and anti-thrombotic properties. Accordingly, we assessed the hypothesis that statin use may modulate stroke severity in AF. Methods: Consecutive IS admissions were identified from 2006-2010. All events were subject to CT or MRI and assessed for functional independence at discharge using modified Rankin scale (mRS). AF was confirmed by ECG at presentation or within the prior 6 months in all cases. Covariates were abstracted from the medical record. To account for confounding by treatment, we used multivariable logistic regression analysis adjusted using inverse probability weighting. Results: We identified 1,030 AF-related IS; mean age was 77, 56% were female, mean CHA 2 DS 2 VASC score was 4.8 designating high baseline stroke risk. IS resulted in severe neurological deficit or death (mRS ≥ 4) for 69%; 21% died within 30-days. Severe stroke was associated with older age, diabetes, dementia, prior ischemic stroke, prior venous thromboembolism, and CKD (Table). Baseline statin use was associated with a 33% reduced risk of sustaining a severe stroke. Conclusion: Strokes in AF are associated with high morbidity and mortality. Clinical markers of thrombophilia, including prior IS, DVT, and PE, were significantly associated with severe strokes. Diabetes and CKD independently increased this risk. Statin use resulted in less severe outcomes. Advancing our basic understanding of these interrelated thrombogenic pathways will inform clinical interventions to reduce these devastating outcomes.

Incidence and prediction of ischemic stroke among atrial fibrillation patients with end-stage renal disease requiring dialysis.

Renal dysfunction is a significant risk factor for ischemic stroke in atrial fibrillation (AF). However, the incidence of ischemic stroke and how to predict its occurrence among AF patients with end-stage renal disease (ESRD) are unclear. The purpose of this study was to compare the CHADS2 and CHA2DS2-VASc scores for stroke risk stratification in AF patients with ESRD. A total of 10,999 AF patients with ESRD undergoing renal replacement therapy who were not receiving oral anticoagulants or antiplatelet agents were identified from Taiwan's National Health Insurance Research Database. The study end-point was occurrence of ischemic stroke. The median (interquartile) CHADS2 and CHA2DS2-VASc scores for the study cohort were 3 (2-5) and 5 (4-7), respectively. During follow-up, 1217 patients (11.7%) experienced ischemic stroke, with an incidence rate of 6.9 per 100 person-years. In Cox regression models, the CHADS2 and CHA2DS2-VASc scores both were significant predictors of ischemic stroke. C-indexes for CHADS2 and CHA2DS2-VASc were 0.608 and 0.682, respectively (P < .001). CHA2DS2-VASc improved the net reclassification index by 4.8% compared with CHADS2 (P < .0001). Among 1409 patients with a CHADS2 score of 0 or 1, the CHA2DS2-VASc score ranged from 1 to 4, with event rates ranging from 2.1 to 4.7 per 100 person-years. The CHA2DS2-VASc score was useful in predicting ischemic stroke in AF patients with ESRD undergoing dialysis and was superior to the CHADS2 score. The net clinical benefit balancing stroke reduction against major bleeding with anticoagulation in these high-risk patients remains to be defined.

Incidental MRI findings of left ventricular myocardial scar in atrial fibrillation patients is associated with increased stroke risk

Background Left ventricular late gadolinium enhancement (LV-LGE) is a known incidental cardiac magnetic resonance (CMR) finding in atrial fibrillation (AF) patients and has recently been associated with increased mortality [1]. While LV-LGE is an indicator of poor prognosis in patients with cardiomyopathy, data on the clinical significance of incidental findings of LV-LGE in AF patients is still unavailable. We aimed to evaluate the association of this incidental finding to ischemic stroke in atrial fibrillation.

Antithrombotic therapy for the secondary prevention of ischemic stroke related to atrial fibrillation: ESC/ACC/ACCP Guidelines

Cardiologia CROATICA Aim of this article is to present the state-of-the-art antithrombotic therapy for the secondary prevention of cardioembolic stroke due to new ESC, ACC, and ACCP guidelines which are the key-opinion guidelines in atrial fibrillation (AF). The statements are based on CHADS2 scoring calculation as well as newly developed CHA2DS2-VASc. Statements: for the patients (pts) with a history of ischemic stroke (IS) or TIA and AF, including paroxysmal AF, guidelines recommend oral anticoagulation (Grade IA), aspirin (Grade IB), or aspirin and clopidogrel (Grade IB). In pts with a history of IS or TIA and AF, guidelines suggest dabigatran 150 mg bid over adjusted-dose VKA (INR 2.0-3.0) (Grade IIB). ESC guidelines recommend for pts with CHA2DS2VASc Score 2, VKA therapy (INR 2,0-3,0), or direct thrombin inhibitor dabigatran, or an oral direct Xa factor inhibitors — rivaroxaban or apixaban (Grade IA). In pts with a history of IS or TIA and AF, who are unsuitable for or choose not to take an oral anticoagulant, guidelines recommend dual therapy, aspirin and clopidogrel (Grade IB). Recommendation is that oral anticoagulation should generally be initiated within 1 to 2 weeks after stroke onset. Earlier anticoagulation can be considered for pts at low risk of bleeding complications i.e. patients with a small infarct burden and no evidence of hemorrhage on brain imaging. Delaying anticoagulation should be considered for pts at high risk of hemorrhagic complications — those with extensive infarct burden or evidence of significant hemorrhagic transformation on brain imaging. In patients with a history of noncardioembolic IS or TIA, guidelines recommend long-term treatment with aspirin (75-100 mg once daily), clopidogrel (75 mg once daily), aspirin/extended-release dipyridamole (25 mg/200 mg bid), or cilostazol (100 mg bid) (Grade IA), VKA (Grade IB), the combination of clopidogrel plus aspirin (Grade IB), or triflusal (Grade IIB). Of the recommended antiplatelet regimens, guidelines suggest clopidogrel or aspirin/extended-release dipyridamole over aspirin (Grade IIB) or cilostazol (Grade IIC). Conclusions: It is an ongoing trend that recommendations follow CHADS2 scoring calculation as well as CHA2DS2VASc Score. Standard of care is based on net clinical benefit i.e. balance between clinical/prevention benefit and safety profile. Still there is a question mark: what to suggest for patients who are unsuitable for oral anticoagulants, for reasons other than major bleeding risk.

Prevalence of atrial fibrillation in intracerebral hemorrhage

Oral anticoagulation (OAC) is an effective preventive therapy for ischemic stroke in atrial fibrillation (AF). The management of anticoagulation in AF patients with previous intracerebral hemorrhage (ICH) is challenging. The aim of this study was to determine the prevalence of AF after acute ICH in a consecutive monocenter cohort, and to document the subsequent management with respect to OAC. Consecutive patients with spontaneous ICH were prospectively included within 19 months. Diagnosis of AF was based on medical history, 12-lead electrocardiogram (ECG), 24-h and continuous ECG monitoring. CHADS₂ scores and patient medication were recorded at admission and after 3 months. Additionally, after 3 months mortality, the management of anticoagulation and a newly detected AF were assessed. In total, 206 ICH patients were eligible for data analysis. After 3 months, AF had been diagnosed in 64/206 ICH patients (31.1%). Mortality after 3 months was higher in patients with AF in univariate analysis (45.3% vs. 31.0%). After adjusting for comorbidities and OAC use, AF did not remain an independent predictor for mortality. In total, 35 patients with AF survived 3 months. Of these, CHADS₂ score was 2 (2/3, median, interquartile range (IQR)) and 27/35 patients had an indication for OAC with respect to the CHADS₂ score, but only 25.7% had been (re-)started on OAC. No consistent factors for deciding whether to initiate OAC treatment could be identified. Atrial fibrillation is a frequent comorbidity in patients suffering an ICH. Our findings underline the prevailing uncertainty regarding the anticoagulation management of AF after ICH.

Abstract TP202: Atrial Fibrillation In Young Stroke Patients: Do We Underestimate Its Prevalence?

BACKGROUND: Our knowledge of the presence of atrial fibrillation (AF) in young stroke patients is scarce. Our objective was to analyze the frequency of AF in ischemic stroke (IS) patients up to 50 years of age and its relationship with stroke severity and outcomes. METHODS: Prospective observational study of consecutive IS patients up to 50 years of age admitted to a stroke center during a five-year period (2007-2011). A complete cardiology study was performed with daily electrocardiogram (ECG) and cardiac monitoring for 72 hours as well as echocardiography. In cases of stroke of unknown etiology, a 24-hour Holter monitoring was performed, which was repeated as necessary. We analyzed baseline data, previously or newly diagnosed AF, structural heart disease (SHD) (valvulopathy/cardiomyopathy), stroke severity on admission measured by the NIHSS (moderate-severe stroke if NIHSS≥5) and 3-month outcomes according to the mRS (good outcome if mRS ≤2). AF was classified as AF associated with SHD (AF-SHD) and AF not associated with SHD (AF-NSHD). RESULTS: One hundred fifty-seven patients were included (mean age 41.1 years, 58.6% male). Sixteen subjects (10.2%) presented AF, 5 with AF-NSHD and 11 with AF-SHD. AF was previously known in 10 patients (6.4%), 2 with AF-NSHD and 8 with AF-SHD. A multivariate analysis showed an independent association between AF and moderate-severe IS (OR 3.882, 95%CI: 1.277-11.799), but AF was not an independent prognostic factor. CONCLUSION: AF is present in up to 10% of young patients with IS and is associated with increased NIHSS scores.

Novel Oral Anticoagulants in Atrial Fibrillation: A Meta‐analysis of Large, Randomized, Controlled Trials vs Warfarin

Warfarin reduces ischemic stroke in atrial fibrillation, but has numerous limitations. Novel oral anticoagulants provide more predictable anticoagulation with fewer shortcomings. Novel oral anticoagulants are superior to warfarin to prevent stroke or systemic embolism. Phase III randomized warfarin-controlled trials enrolling >3000 patients that reported clinical efficacy and safety of novel oral anticoagulants in patients with atrial fibrillation were identified from MEDLINE, Embase, and Cochrane Central Register of Controlled Trials through October 2012. Two reviewers extracted data; differences were resolved by consensus. The end points analyzed were stroke or systemic embolism (primary efficacy composite); all-cause mortality, ischemic stroke, systemic embolism (individually, secondary efficacy); and hemorrhagic stroke, major bleeding (individually, safety). The Mantel-Haenszel method was used to calculate pooled relative risk (RR) and 95% confidence intervals (CI) from fixed-effects (if homogenous) or random-effects models (if heterogeneous). In 5 studies of 51895 patients, the composite of stroke or systemic embolism (RR: 0.82; 95% CI: 0.69-0.98; P = 0.03) and all-cause mortality (RR: 0.91; 95% CI: 0.85-0.96; P = 0.0026, respectively) were reduced with the novel agents. Factor Xa inhibitors significantly reduced the primary composite (RR: 0.84; 95% CI: 0.74-0.94; P = 0.004) and all-cause mortality (RR: 0.91; 95% CI: 0.84 - 0.98; P = 0.01). Direct thrombin inhibitor achieved results similar to the overall meta-analysis (drug class-outcome interactions P = 0.47 for primary outcome, P = 1.00 for mortality). Compared with warfarin, novel anticoagulants markedly reduced hemorrhagic stroke (RR: 0.51; 95% CI: 0.41-0.64; P < 0.0001). Novel oral anticoagulants may be superior to warfarin in patients with atrial fibrillation, reducing the composite of stroke or systemic embolism and lowering all-cause mortality. The benefit is largely due to fewer hemorrhagic strokes.

Atrial Fibrillation in Ischemic Stroke

Atrial fibrillation (AF) increases the risk of stroke and is associated with poor stroke outcomes. Limited tools are available to evaluate clinical outcomes and response to thrombolysis in stroke patients with AF. We applied the iScore (http://www.sorcan.ca/iscore), a validated risk score, to consecutive patients with an acute ischemic stroke admitted to stroke centers in the Registry of the Canadian Stroke Network. The main outcome considered was a favorable outcome (defined as a modified Rankin scale 0-2) at discharge after thrombolysis. Secondary outcomes included intracerebral hemorrhage, death at 30 days, and at 1 year stratified by terciles of the iScore. Among 12 686 patients with an acute ischemic stroke, 2185 (17.2%) had AF. Overall, AF patients had higher risk of death at 30 days (22.3% versus 10.2%; P<0.0001), 1 year (37.1% versus 19.5%; P<0.0001) and death or disability at discharge (69.7% versus 54.7%; P<0.0001) compared with non-AF patients. After adjustment, thrombolysis was associated with a favorable outcome for patients without AF (relative risk, 1.18; 95% CI, 1.10-1.27), but no benefit was observed for patients with AF (relative risk, 0.91; 95% CI, 0.71-1.17). There was a modestly increased risk of intracranial hemorrhage (any type) (16.5% versus 11.6%; relative risk, 1.42; 95% CI, 1.05-1.91) after thrombolysis among AF compared with non-AF patients. In the logistic regression analysis, there was an interaction between tPA and iScore for a favorable outcome (P-value interaction <0.001). The interaction also was significant (P<0.0012) among patients without AF, but did not reach significance (P=0.17) in patients with AF. Stroke patients with AF have higher mortality, greater risk of intracerebral hemorrhage, and a similar response trend to thrombolysis compared with non-AF patients.

Troponin Elevation Predicts Atrial Fibrillation in Patients with Stroke or Transient Ischemic Attack

Atrial fibrillation (AF) is a major cause of ischemic stroke. Cardiac troponin (cTnI) is a marker of myocardial damage and may predict arrhythmia. We sought to determine if increased cTnI levels were a predictor of new-onset AF in ischemic stroke or patients with transient ischemic attack (TIA). Consecutive patients who presented to Charles-Lemoyne Hospital between October 2006 and November 2010 with a diagnosis of acute ischemic stroke or TIA, without a history of AF, with a baseline measurement of cTnI were included in the study. The primary outcome was new-onset AF on 24-hour Holter measurement within 1 week of admission in patients without AF on the baseline electrocardiogram (ECG). Secondary outcomes included AF on Holter measurement, death, myocardial infarction (MI), and stroke within 3 months. A total of 408 patients were included. Forty-six patients (11.3%) had elevated cTnI levels. These patients were older and had a higher prevalence of coronary artery disease and diabetes. AF on baseline ECG or 24-hour Holter measurement was present in 51 patients (12.5%) and was more frequent among patients with increased cTnI levels compared to patients with normal cTnI levels (34.7% vs 9.7%; P = .004 multivariate analysis). Elevated cTnI levels also predicted the composite outcome of stroke, MI, and death at 3 months (50.0% vs 16.1%; P = .0001). cTnI elevation predicts new-onset AF on 24-hour Holter measurement in patients with acute ischemic stroke or TIA and may indicate a poorer prognosis and a higher risk of stroke, MI, and death at 3 months.

Effect of Warfarin on Outcomes in Septuagenarian Patients With Atrial Fibrillation

Anticoagulation has been shown to decrease ischemic stroke in atrial fibrillation (AF). However, concerns remain regarding their safety and efficacy in those ≥70 years of age who constitute most patients with AF. Of the 4,060 patients (mean age 65 years, range 49 to 80) in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial, 2,248 (55% of 4,060) were 70 to 80 years of age, 1,901 of whom were receiving warfarin. Propensity score for warfarin use, estimated for each of the 2,248 patients, was used to match 227 of the 347 patients not on warfarin (in 1:1, 1:2, or 1:3 sets) to 616 patients on warfarin who were balanced in 45 baseline characteristics. All-cause mortality occurred in 18% and 33% of matched patients receiving and not receiving warfarin, respectively, during up to 6 years (mean 3.4) of follow-up (hazard ratio [HR] when warfarin use was compared to its nonuse 0.58, 95% confidence interval [CI] 0.43 to 0.77, p <0.001). All-cause hospitalization occurred in 64% and 67% of matched patients receiving and not receiving warfarin, respectively (HR associated with warfarin use 0.93, 95% CI 0.77 to 1.12, p = 0.423). Ischemic stroke occurred in 4% and 8% of matched patients receiving and not receiving warfarin, respectively (HR associated with warfarin use 0.57, 95% CI 0.31 to 1.04, p = 0.068). Major bleeding occurred in 7% and 10% of matched patients receiving and not receiving warfarin, respectively (HR associated with warfarin use 0.73, 95% CI 0.44 to 1.22, p = 0.229). In conclusion, warfarin use was associated with decreased mortality in septuagenarian patients with AF but had no association with hospitalization or major bleeding.

Prolonged Rhythm Monitoring for the Detection of Occult Paroxysmal Atrial Fibrillation in Ischemic Stroke of Unknown Cause

Atrial fibrillation (AF), commonly encountered in patients with ischemic stroke and transient ischemic attack (TIA), confers a 5-fold increased risk of ischemic stroke.1,2 AF-related strokes are associated with an ≈50% increased risk of disability and 60% increased risk of death at 3 months compared with strokes of other etiologies.3 Paroxysmal AF (PAF), a self-terminating recurrent form of cardiac arrhythmia that comprises between 25% and 62% of AF cases, may present as a brief single episode of arrhythmia or as clusters of abnormal rhythm of variable duration, sometimes evolving into a more persistent or permanent form.4 The self-terminating nature of PAF may lead to its underdiagnosis and consequent use of less effective treatment strategies (aspirin instead of oral anticoagulation) in poststroke patients. To address the underdiagnosis of PAF in patients with ischemic stroke and TIAs, several treatment guidelines have singled out the identification of PAF as an important goal after a stroke/TIA.5–8 The diagnosis of PAF, however, poses a challenge. Several features of AF (such as its brief duration, episodic frequency, and asymptomatic presentations) make its detection difficult and elusive to bedside screening measures, such as pulse monitoring and routine ECGs. To date, several studies have explored the use of prolonged noninvasive and invasive cardiac monitoring devices to identify AF but with variable success. After detection of AF, a cardioembolic mechanism is often inferred and anticoagulation occasionally prescribed for secondary stroke prevention. The routine use of cardiac monitoring to identify patients with PAF who will benefit from anticoagulation has been reported to be cost-effective.9 In this review, we provide an overview of the different methods of cardiac monitoring, summarize studies that investigated the incidence of PAF after stroke, and highlight gaps in our understanding of the pathogenic and prognostic significance of AF …

Edoxaban: Pharmacological principles, Preclinical and early-phase Clinical Testing

Vitamin K antagonists have been the cornerstone of oral antithrombotic therapy to help prevent ischemic stroke in atrial fibrillation (AF) and reduce venous thromboembolic events. Despite proven clinical benefit, vitamin K antagonists have several limitations, including a narrow therapeutic window, slow onset/offset of action, need for close monitoring and significant drug/food interactions, highlighting the need for alternative therapies. Recently, the direct thrombin inhibitor dabigatran was approved by the US FDA for use in AF, and several factor Xa inhibitors are in late-stage clinical testing. Edoxaban is a novel, oral, reversible, direct factor Xa inhibitor with rapid absorption and predictable dose-dependent anticoagulation effects. Early clinical studies have shown promising results and it is currently undergoing large-scale Phase III trials for stroke prevention in AF and venous thromboembolic event prophylaxis and treatment. This review provides an overview of the current understanding, clinical trial results and pharmacology of edoxaban.

Stroke Prevention in Atrial Fibrillation: Atrial Appendage Closure

The left atrial appendage (LAA) is the primary nonvalvular cause of cardioembolic stroke in patients with atrial fibrillation (AF). Warfarin and direct thrombin inhibitors such as dabigatran are presumed to prevent formation of LAA thrombus, and are first-line treatments to prevent ischemic stroke in AF. However, these medications carry many contraindications such as hemorrhage, and can interact with many drugs and supplements. Epicardial and endovascular techniques for occlusion of LAA are being explored, whether to mitigate the need for anticoagulation in patients at risk of bleeding or as a first-line therapy to reduce the risk of thromboembolic stroke. The purposes of this article are to 1) review the LAA structure and its potential contribution to ischemic stroke; 2) discuss the results of surgical and endovascular trials of LAA occlusion on risk of stroke and adverse events in AF patients; and 3) present early data on devices in development.

Stroke prevention in atrial fibrillation patients

Importance of the field: Atrial fibrillation (AF) is the most common cardiac arrhythmia encountered in clinical practice and is associated with an increased risk of stroke, mortality and significant morbidity. Given the rapidly increasing incidence and prevalence of AF, and the resulting public health burden of the consequences associated with this arrhythmia, stroke prevention is an extremely important topic.Areas covered in this review: This review covers the epidemiology of AF, the pathophysiology of ischemic stroke in AF and current antithrombotic therapy choices for stroke prevention in this condition. In addition, this article discusses important topics such as the assessment of stroke risk stratification and bleeding risk assessment, which are key issues in deciding upon thromboprophylaxis for AF patients. Finally, the review highlights the advent of new anticoagulant therapies and discusses the future challenges for researchers in this area.What the reader will gain: This review summarizes all of the major antithrombotic trials conducted in AF patients over the last twenty years and highlights the importance of anticoagulation therapy for the prevention of stroke, after appropriate individual stroke and bleeding risk assessment.Take home message: Assessment of individual stroke risk and bleeding risk is key in determining appropriate thromboprophylaxis for AF patients, given the associated thromboembolic and hemorrhagic complications. The availability of newer, safer and more convenient drugs will mean that oral anticoagulation is available for a larger proportion of AF patients who may benefit from it.

Occult atrial fibrillation in ischemic stroke

Physicians frequently evaluate patients with recent ischemic strokes or transient ischemic attacks (TIA) and perform diagnostic evaluations only to find no clear demonstrable etiology in fully one-third of cases. Cryptogenic stroke remains a diagnostic category of exclusion and encompasses a broad range of patients with varied risk factors, comorbid conditions, and radiographic patterns of cerebral infarction. In contrast, atrial fibrillation (AF) is a common and well-defined cause of ischemic stroke, representing 50% of cardioembolic stroke and 10% of all ischemic strokes, often resulting in severe neurologic disability.1 AF can be readily diagnosed by electrocardiography, and has known risk factors, pathophysiology, and therapeutic options, including anticoagulation. Approximately 25% of patients with AF have intermittent AF that is often asymptomatic and undetected by conventional methods of brief cardiac telemetry monitoring.1,2 Patients who are initially diagnosed with cryptogenic stroke or TIA can be found subsequently to have intermittent AF, suggesting that efforts to improve AF detection are warranted. An optimal telemetry monitoring method for the detection of occult AF could identify stroke patients at risk for recurrent cardioembolic stroke and a subgroup that may benefit from anticoagulation. Paroxysmal AF (PAF) is believed to carry the same stroke risk as continuous AF; however, patients with PAF exhibit a …

230 Unexpected low prevalence of atrial fibrillation in cryptogenic ischemic stroke: a prospective continuous monitoring study

Ischemic stroke (IS) is a frequent pathology, burdened by high rate of recurrence and significant morbidity and mortality. There are several causes of IS, affecting prognosis, outcomes and management, but in many cases the etiology remains undetermined despite comprehensive research. We hypothezised that atrial fibrillation (AF) was largely involved in this pathology but was underdiagnosed by standard methods. The aim of this study was to determine the incidence of AF in cryptogenic IS, by using continuous monitoring of the heart rate over several months. The secondary objective was to test the predictive value of atrial vulnerability study towards spontaneous AF. We prospectively enrolled 24 patients under 75 years: 15 men and 9 women of mean age 48.8± 13.6 years who experienced cryptogenic IS presumed of cardioembolic mechanism within the last 4 months. Any cause of IS was excluded by normal 12-lead ECG, 24-hour Holter monitoring, echocardiography, cervical Doppler, haematological and inflammatory tests. All patients underwent electrophysiological study. 7 patients (29.2%) had inducible arrhythmia during programmed atrial stimulation and 9 (37.5%) had a latent vulnerability index (LVI) <2.5. Patients were secondarily implanted with an implantable loop recorder (ILR) (Medtronic™ Reveal Plus 9526) to look for spontaneous AF over a mean follow-up interval of 14.5 months. No sustained arrhythmia was found. Only one patient had non significant AF access (<30 s). In this patient, it was not triggered sustained arrhythmia but the LVI was low. This study shows that contrary to what was expected, AF does not appear to be a common pathology in patients under 75 years with unexplained IS. The use of ILR should not be generalized in the systematic assessment of these patients because of its unprofitability. Finally this study attests the poor value of atrial vulnerability study for predicting spontaneous AF in such patients.

Should Patient Characteristics Influence Target Anticoagulation Intensity for Stroke Prevention in Nonvalvular Atrial Fibrillation?

Randomized trials and observational studies support using an international normalized ratio (INR) target of 2.0 to 3.0 for preventing ischemic stroke in atrial fibrillation. We assessed whether the INR target should be adjusted based on selected patient characteristics. We conducted a case-control study nested within the ATRIA cohort's 9217 atrial fibrillation patients taking warfarin to define the relationship between INR level and the odds of thromboembolism (TE; mainly stroke) and of intracranial hemorrhage (ICH) relative to INR 2.0 to 2.5. We identified 396 TE cases and 164 ICH cases during follow-up. Each case was compared with 4 randomly selected controls matched on calendar date and stroke risk factors using matched univariable analyses and conditional logistic regression. We explored modification of the INR-outcome relationships by the following stroke risk factors: prior stroke, age, and CHADS(2) risk score. Overall, the odds of TE were low and stable above INR 1.8. Compared with INR 2.0 to 2.5, the relative odds of TE increased strikingly at INR <1.8 (eg, odds ratio, 3.72; 95% CI, 2.67 to 5.19, at INR 1.4 to 1.7). The odds of ICH increased markedly at INR values >3.5 (eg, odds ratio, 3.56; 95% CI: 1.70 to 7.46, at INR 3.6 to 4.5). The relative odds of ICH were consistently low at INR <3.6. There was no evidence of lower ICH risk at INR levels <2.0. These patterns of risk did not differ substantially by history of stroke, age, or CHADS(2) risk score. Our results confirm that the current standard of INR 2.0 to 3.0 for atrial fibrillation falls in the optimal INR range. Our findings do not support adjustment of INR targets according to previously defined stroke risk factors.