Ischemic Stroke Atrial Fibrillation Research Articles

Metabolic Syndrome and Risk of Ischemic Stroke in Atrial Fibrillation: ARIC Study.

Background and Purpose- Metabolic syndrome (MetS), a prothrombotic state, is associated with an increased risk of atrial fibrillation (AF) and stroke. The CHA2DS2-VASc score does not account for the MetS components of prehypertension, prediabetes mellitus, abdominal obesity, elevated triglycerides, and low HDL (high-density lipoprotein). Data are limited on the association of MetS with stroke in AF, independent of CHA2DS2-VASc variables. Our aim was to identify MetS components associated with ischemic stroke in participants with AF in the ARIC study (Atherosclerosis Risk in Communities). Methods- We included 1172 participants with incident AF within 5 years of measurement of MetS components. MetS was defined by ATP criteria and International Diabetes Federation criteria. Incident ischemic stroke was physician adjudicated. Multivariable Cox proportional hazards regression was used to assess the association of MetS components with stroke. Results- After a median follow-up of 14.8 years, there were 113 ischemic stroke cases. Of the individual MetS components, low HDL was borderline associated with increased stroke risk (hazard ratio, 1.48 [95% CI, 0.99-2.21]) after adjustment for CHA2DS2-VASc variables while the remaining MetS variables were not associated with stroke risk. The presence of ≥3 components of MetS was not significantly associated with ischemic stroke after adjustment for CHA2DS2-VASc variables (hazard ratio, 1.38 [95% CI, 0.91-2.11]). The risk of stroke increased by 13% for each additional component of MetS; however, this association was borderline significant (hazard ratio, 1.13 [95% CI, 0.99-1.28]). Conclusions- The presence of MetS was not significantly associated with ischemic stroke after adjustment for CHA2DS2-VASc variables. Consideration of MetS is unlikely to improve stroke prediction in AF.

Protocol for AREST: Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation-A Randomized Controlled Trial of Early Anticoagulation After Acute Ischemic Stroke in Atrial Fibrillation.

Background: Optimal timing to initiate anticoagulation after acute ischemic stroke (AIS) from atrial fibrillation (AF) is currently unknown. Compared to other stroke etiologies, AF typically provokes larger infarct volumes and greater concern of hemorrhagic transformation, so seminal randomized trials waited weeks to months to begin anticoagulation after initial stroke. Subsequent data are limited and non-randomized. Guidelines suggest anticoagulation initiation windows between 3 and 14 days post-stroke, with Class IIa recommendations, and level of evidence B in the USA and C in Europe.Aims: This open-label, parallel-group, multi-center, randomized controlled trial AREST (Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation) is designed to evaluate the safety and efficacy of early anticoagulation, based on stroke size, secondary prevention of ischemic stroke, and risks of subsequent hemorrhagic transformation.Methods: Subjects are randomly assigned in a 1:1 ratio to receive early apixaban at day 0–3 for transient ischemic attack (TIA), 3–5 for small-sized AIS (<1.5 cm), and 7–9 for medium-sized AIS (1.5 cm or greater but less than a full cortical territory), or warfarin at 1 week post-TIA or 2 weeks post-stroke. Large AISs are excluded.Study Outcomes: Primary: recurrent ischemic stroke, TIA, and fatal stroke; secondary: intracranial hemorrhage (ICH); hemorrhagic transformation (HT) of ischemic stroke; cerebral microbleeds (CMBs); neurologic disability [e.g., modified Rankin Scores (mRS), National Institutes of Health Stroke Scale (NIHSS), Stroke Specific Quality of Life scale (SS-QOL)]; and cardiac biomarkers [e.g., AF burden, transthoracic echo (TTE)/transesophageal echo (TEE) abnormalities].Sample Size Estimates: Enrollment goal was 120 for 80% power (two-sided type I error rate of 0.05) to detect an absolute risk reduction of 16.5% postulated to occur with apixaban in the primary composite outcome of fatal stroke/recurrent ischemic stroke/TIA within 180 days. Enrollment was suspended at 91 subjects in 2019 after a focused guideline update recommended direct oral anticoagulants (DOACs) over warfarin in AF, excepting valvular disease (Class I, level of evidence A).Discussion: AREST will offer randomized controlled trial data about timeliness and safety of anticoagulation in AIS patients with AF.Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02283294.

Oral anticoagulant prescribing in elderly patients above and below age 80 with atrial fibrillation .

Oral anticoagulation is efficient to prevent ischemic stroke in atrial fibrillation (AF), but in very old patients, physicians always remain cautious to use anticoagulants concerning the bleeding risk. This research aims to investigate the current situation of oral anticoagulation therapy in very old (≥ 80 years) AF patients. We carried out a cross-sectional study in an urban area in China from 2014 to 2016. Characteristics of the very old patients (age ≥80 years) and the younger patients (age < 80 years) were compared. Logistic analysis was used to estimate the association between oral anticoagulation therapy and CHA2DS2-VASc score. A total of 1,000 AF patients were enrolled; 306 were very old patients, and 694 were younger patients. In the very old group, 48.0% were women, and the average age was 84.12±3.62 years. In the younger group, 35.3% were women, and the average age was 66.92±9.02 years. CHA2DS2-VASc score was 2.8±1.7 in the younger group and 4.5±1.5 in the very old group (p< 0.001). The proportion of oral anticoagulation was low in patients with AF (31.8%) and even lower in very old patients compared to younger patients (24.5 vs. 35.0%, p=0.004). Moreover, oral anticoagulation therapy was strongly associated with CHA2DS2-VASc scores only in the younger group, but not in the very old group, which means the very old patients were not treated with oral anticoagulation according to their elevated CHA2DS2-VASc scores. Anticoagulants were underused in AF patients, particularly in very old patients. Evidence is accumulating that the very old patients could still benefit from anticoagulants so that physicians should not exclude such patients from anticoagulation only because of their older age.

Abstract WMP64: Global Longitudinal Peak Strain to Predict Atrial Fibrillation in Ischemic Stroke

Cerebral infarction due to atrial fibrillation is more severe and has a higher risk of death than other stroke subtypes. Anticoagulation reduces the risk of recurrence in patients with atrial fibrillation, and so it is crucial to find atrial fibrillation in stroke patients. In the present study, we investigated whether left atrial volume index (LAVI) and global longitudinal peak strain (GLPS) on speckle echocardiography could discriminate a high-risk group of atrial fibrillation in stroke patients. We prospectively enrolled 678 ischemic patients. Stroke subtypes were determined by the consensus of experienced neurologists, using a validated MRI-based algorithm. Left ventricular GLPS was measured averaging by speckle tracking imaging echocardiography from 4-chamber, 2-chamber, and the apical longitudinal long-axis view with breathing hold and an echocardiogram recording. To evaluate the predictability of LAVI and GLPS for the presence of atrial fibrillation, we used the optimism-corrected c-statistics and the net reclassification improvement with prespecified atrial fibrillation risk categories of low (10%), intermediate (10% to 30%), and high (≥30%). Patients with atrial fibrillation were likely to be older and to have more vascular risk factors. LAVI (74 ml/m 2 vs. 42 ml/m 2 ) and GLPS (-14% vs. -17%) were higher in patients with atrial fibrillation. Age (adjusted odds ratio 1.04, 95% confidence interval 1.02-1.07), LAVI (1.07, 1.06-1.09), and GLPS (1.08, 1.03-1.12) were independently associated with atrial fibrillation. As a base model, age and LAVI had a C-statistics of 0.89 (95% confidence interval 0.86 - 0.93). When GLPS levels were added to a base-model, net reclassification improvement was 6.1% (p = 0.03), albeit area under curve marginally improved (C-statistics = 0.90, 95% confidence interval 0.87 - 0.93, p = 0.058) compared to a base model. In patients with ischemic stroke, GLPS levels combined with LAVI were associated with the presence of atrial fibrillation. Our data imply that rigorous screening tests to detect atrial fibrillation may be warranted for the patients with high LAVI and GLPS levels.

Abstract WMP62: Duration of Implantable Cardiac Monitoring and Detection of Atrial Fibrillation in Ischemic Stroke Patients: A Systematic Review and Meta-analysis

Introduction: Although current guidelines indicate that the clinical benefit of prolonged cardiac monitoring for atrial fibrillation (AF) detection in ischemic stroke (IS) patients remains uncertain, clinical trials suggest that implantable cardiac monitors (ICMs) substantially increase AF detection due to prolonged monitoring duration. Methods: In the present systematic review and meta-analysis we sought to investigate the association of ICM duration with the yield of AF detection in IS patients. We also assessed whether IS subtype, individual patient characteristics and elapsed time between IS onset and CM implantation may also impact the probability of AF detection. We included studies reporting AF detection rates by ICM in IS patients with negative initial AF screening. We excluded studies reporting prolonged cardiac monitoring with devices other than ICM, not providing AF detection rates or monitoring duration and reporting overlapping data for the same population. Random-effects model was used to calculate the pooled estimates in all subgroup and univariate meta-regression analyses. Results: We included 28 studies (4531 patients; mean age:65 years; 52% men). In meta-regression analyses the proportion of AF detection by ICM was independently associated with monitoring duration (coefficient=0.015,95%CI:0.005-0.024) and mean patient age (coefficient=0.009, 95%CI:0.003-0.015). No association was detected with other patient characteristics, including IS subtype (cryptogenic vs. embolic stroke of undetermined source) or time from IS onset to CM implantation. In subgroup analyses significant differences (p&lt;0.001) in the AF detection rates were documented according to ICM duration (&lt;6 months: 4%, 95%CI: 3%-6%; ≥6 months &amp; ≤12 months: 20%, 95%CI: 17%-24%; &gt;12 months &amp; ≤24 months: 26%, 95%CI: 23%-30%; &gt;24 months: 34%, 95%CI: 30%-39%). Conclusion: Extended duration of ICM monitoring appears to be the only factor that increases substantially the yield of AF detection in patients with IS and initial negative AF screening. IS subtype and individual patients characteristics, except age, are not related to the probability of AF detection.

Comparison of stroke risk according to sinus node disease, atrial fibrillation and bradycardia-tachycardia syndrome: A French nationwide cohort-study

Atrial fibrillation (AF) may commonly be associated with sinus node disease (SND) presenting as the so-called bray-tachy syndrome (BTS). BTS and AF are known to be at risk for ischemic stroke (IS). It remains unclear whether the risk of IS is similar in patients with isolated SND. Our objective was to compare the risk of IS in AF, SND and BTS patients and to identify risk factors of stroke in patients with SND. This French longitudinal cohort study was based on the national hospitalization database, the Programme de médicalisation des systèmes d’information (PMSI). We included all patients over 18 y.o. in France from January 2010 to December 2015 hospitalized with a main or related diagnosis of AF or SND. Baseline characteristics were pooled into a multivariate Cox model to identify significant predictors of IS. Of 1,732,412 patients included after exclusion of pacemaker or implantable cardiac defibrillator patients (PM/ICD), 1,601,435 (92.44%) had AF, 102,849 (5.94%) SND and 28,128 (1.62%) BTS. Compared to patients with AF or BTS, those with SND were younger, had a lower CHA2DS2-VASc score. Incidence of IS during follow-up was higher in AF than in BTS patients (yearly rate 4.90% vs. 2.73%, P < 0.0001) and in AF than in SND (yearly rate 4.90% vs. 1.97%, P < 0.0001). In patients with SND, main independent predictors of IS during follow-up were age ≥ 75 y.o., hypertension, vascular disease, alcohol-related diagnoses and lung disease. Patients with SND and a CHA2DS2-VASc score ≥ 2 had a worse thromboembolic prognosis with a hazard ratio of 2.34 (95% CI 2.071–2.644, P < 0.0001) for IS occurrence compared to those with CHA2DS2-VASc score = 0 or 1. Patients with SND have a lower risk of thromboembolic events than those with AF or BTS. However, SND patients with a CHA2DS2-VASc score ≥ 2 had a markedly higher risk of IS during follow-up and may need specific considerations.

GW29-e1534 Heart failure status evaluated through different ways and risk of ischemic stroke in atrial fibrillation patients with coronary stenting

Although congestive heart failure (CHF) has been recogonized as a key factor in predicting ischemic stroke in nonvalvular atrial fibrillation (NVAF) patients, measures to evaluate CHF haven’t been investigated, especially in NVAF patients complicated with coronary artery diseases and coronary

Age Threshold for Ischemic Stroke Risk in Atrial Fibrillation.

Background and Purpose- Although older age is one of the most important risk factor for stroke in atrial fibrillation (AF), the appropriate age threshold (eg, CHA2DS2-VASc score [congestive heart failure, hypertension, age ≥75 years (doubled), diabetes mellitus, prior stroke or transient ischemic attack (doubled), vascular disease, age 65-74 years, female], 1 point for age 65-74 years, 2 points for age ≥75 years) for increased risk is controversial because actual age thresholds may differ between countries and ethnic groups. We investigated the age threshold for ischemic stroke risk among Asian AF patients. Methods- Using National Health Insurance Service database, including 426 650 oral anticoagulant-naive nonvalvular AF patients from 2005 to 2015, with ≤2 nongender-related CHA2DS2-VASc risk scores (CHA2DS2-VASc score 0-2 in males, 1-3 in females), we assessed the risk of ischemic stroke in AF patients according to the age. Results- Patients who fulfill the age risk criterion (age, 65-74 years) without other risk factors showed a significantly higher risk of stroke (4.76 per 100 person-years [100PY]; adjusted hazard ratio, 2.25; 95% confidence interval [CI], 2.17-2.36) compared with patients with 1 risk score other than age (1.87/100PY). Patients aged 55 to 59 years with no risk factors showed similar risk of stroke (1.94/100PY; adjusted hazard ratio, 0.95; 95% confidence interval, 0.90-1.00) than patients with 1 risk score (2.06/100PY). Patients aged 65 to 69 years and no other risk factors had similar stroke risk (4.08/100PY; adjusted hazard ratio, 0.93; 95% confidence interval, 0.90-0.97) than patients with 2 nongender-related risk scores (4.42/100PY). Conclusions- Older age is the most important predictor of ischemic stroke in AF, particularly for patients with low to intermediate risk of stroke. These nationwide data suggest lowering the current age threshold (age, ≥65 years) in the CHA2DS2-VASc score to age ≥55 years might be appropriate among Asian patients with AF.

Digoxin and Amiodarone on the Risk of Ischemic Stroke in Atrial Fibrillation: An Observational Study.

Purpose: The present study compared the risk of ischemic stroke in atrial fibrillation (AF) patients receiving digoxin and amiodarone.Methods: A retrospective cohort study was conducted using the longitudinal population-based database of Taiwan’s National Health Insurance program. Patients with AF who received amiodarone or digoxin and were considered to have exposed to study drugs consecutively over 180 days during 2000–2010 were enrolled and divided into three groups: those who received amiodarone, digoxin, and amiodarone plus digoxin. All patients were followed from the index date to the occurrence of ischemic stroke, death, withdrawal from the insurance program, or December 31, 2011. Cox proportional hazard regression models were applied to determine the risk of ischemic stroke and associated risk factors.Results: The amiodarone, digoxin, and amiodarone plus digoxin cohorts comprised 797, 1419, and 376 patients, respectively. Overall, the patients who received digoxin (HR = 1.80; 95% CI = 1.41–2.31) or amiodarone plus digoxin (HR = 2.00; 95% CI = 1.49–2.68) had a higher risk of ischemic stroke, compared with those who received amiodarone. This risk was particularly at CHA2DS2VASc score of 2–5, but disappeared in those who received clopidogrel in the digoxin cohort. The risk of ischemic stroke in the amiodarone plus digoxin cohort did not differ significantly from that in the digoxin cohort (HR = 1.14; 95% CI = 0.90–1.44).Conclusion: Atrial fibrillation patients receiving digoxin are associated with a higher risk of ischemic stroke than are those receiving amiodarone. It is prudent to assess the stroke risk prior to applying treatment strategy for patients with AF.Strengths and Limitations of This Study - This study is a population-based design with a completeness and accuracy of data, national coverage in both study and control cohorts. All insurance claims were double-checked by medical specialists for peer review. - Information about serum levels of the drugs, coagulation status, and types of AF were unavailable in this administrative database.

Abstract TP172: Newly Diagnosed Atrial Fibrillation in Ischemic Stroke is an Independent Predictor of Mortality in Underserved Populations

Stroke is a major cause of death and disability in the United States and underserved communities are at higher risk for complications, severity and recurrence of stroke compared to the general population. Atrial fibrillation (A-fib) predisposes to ischemic stroke occurrence; however, newly diagnosed A-fib at the time of stroke, and its predictive value in the outcome of underserved patients has not been reported. Aim: To explore the clinical significance of newly diagnosed A-fib among underserved populations with ischemic stroke. Methods: Retrospective cohort of patients with acute ischemic stroke diagnosis at John H. Stroger Hospital in 2014. New A-fib confirmed by electrocardiography. Stroke events were confirmed by magnetic resonance imaging or computed tomography. Given our small event rate we dichotomized National Institute of Health Stroke Scale (NIHSS) into severe (≥15) and non-severe (&lt;15) to make groups comparable. Demographic and potential confounding variables were independently extracted. SPSS version 24 was used and Kaplan Meier and Cox logistic regression with forward modeling were applied. Results: A total of 424 patients for the analysis, mean±SD age of 59.2±11.9 years, mostly male (57.5%), the majority African Americans (59.7%) followed by Hispanics (20.3%). The mean±SD follow up was 22.7±16.6 months, and 24 patients died (5.7%). A-fib was newly diagnosed in 8 (1.9%) patients and a third (37.5%) met indication or accepted anticoagulation. We adjusted for age, hypertension, diabetes, prior stroke, prior A-fib, anticoagulation, alcohol, smoking history and NIHSS. In our model NIHSS ≥15 was the strongest predictor or mortality (HR: 8.04; 95%CI: 2.14-30.25; p&lt;0.01) followed by newly diagnosed A-fib (HR: 5.47; 95%CI: 1.29-23.12; p=0.02). Patients with newly diagnosed A-fib had worse overall survival when compared to those without A-fib (mean 517 days vs 1237 days, p&lt;0.01). Conclusion: Our results are hypothesis generating, and suggest that ischemic stroke secondary to newly diagnosed A-fib carries worse overall survival. It’s plausible that this subset of patients may require a tailored longitudinal plan to reduce risk of poor outcomes in an undeserved population.

Epicardial Fat Thickness and Free Fatty Acid Level are Predictors of Acute Ischemic Stroke with Atrial Fibrillation.

BACKGROUNDIncreased epicardial fat is known to be associated with the presence and chronicity of atrial fibrillation (AF). Free fatty acids (FFAs) are major components of epicardial fat; however, their potential association with AF in ischemic stroke has not been investigated. We aimed to assess the performance of echocardiographic epicardial fat thickness (EFT) and plasma FFA level in identifying patients with ischemic stroke and AF.METHODSWe enrolled a total of 214 consecutive patients (mean age, 66.8 ± 12.3 years; 39.7% women) diagnosed with acute ischemic stroke between March 2011 and June 2014. The patients were divided into two groups: ischemic stroke with AF (n = 35, 16.4%) and ischemic stroke without AF (n = 179, 83.6%).RESULTSThe ischemic stroke with AF group showed significantly higher serum FFA level (1379.7 ± 717.5 vs. 757.8 ± 520.5 uEq/L, p < 0.0001) and EFT (6.5 ± 1.2 vs. 5.3 ± 1.2 mm, p < 0.001) than the group without AF. Multivariable logistic regression analysis demonstrated that age (odds ratio [OR], 1.112), serum FFA level (OR, 1.002), and EFT (OR, 1.740) were independently associated with the ischemic stroke group with AF. EFT and FFA significantly improved the goodness-of-fit and discriminability of the simple regression model including age as a covariate (log likelihood difference, 21.35; p < 0.001; c-index difference, 17.9%; p < 0.001).CONCLUSIONSHigh EFT and serum FFA level were associated with ischemic stroke in patients with AF. Echocardiographic EFT and serum FFA level can play a significant role in identifying ischemic stroke with AF.

Role of rivaroxaban in the management of atrial fibrillation: insights from clinical practice.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and it leads to significant morbidity and mortality, predominantly from ischemic stroke. Vitamin K antagonists, mainly warfarin, have been used for decades to prevent ischemic stroke in AF, but their use is limited due to interactions with food and other drugs, as well as the requirement for regular monitoring of the international normalized ratio. Rivaroxaban, a direct factor Xa inhibitor and the most commonly used non-vitamin K oral anticoagulant, avoids many of these challenges and is being prescribed with increasing frequency for stroke prevention in non-valvular AF. Randomized controlled trial (RCT) data from the ROCKET-AF(Rivaroxaban once daily oral direct Factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation) trial have shown rivaroxaban to be non-inferior to warfarin in preventing ischemic stroke and systemic embolism and to have comparable overall bleeding rates. Applicability of the RCT data to real-world practice can sometimes be limited by complex clinical scenarios or multiple comorbidities not adequately represented in the trials. Available real-world evidence in non-valvular AF patients with comorbidities – including renal impairment, acute coronary syndrome, diabetes mellitus, malignancy, or old age – supports the use of rivaroxaban as safe and effective in preventing ischemic stroke in these subgroups, though with some important considerations required to reduce bleeding risk. Patient perspectives on rivaroxaban use are also considered. Real-world evidence indicates superior rates of drug adherence with rivaroxaban when compared with vitamin K antagonists and with alternative non-vitamin K oral anticoagulants – perhaps, in part, due to its once-daily dosing regimen. Furthermore, self-reported quality of life scores are highest among patients compliant with rivaroxaban therapy. The generally high levels of patient satisfaction with rivaroxaban therapy contribute to overall favorable clinical outcomes.

Clarifying the Role of Hypoxia in Obstructive Sleep Apnea as a Potential Promulgator of Atrial Fibrillation in Ischemic Stroke.

Clarifying the Role of Hypoxia in Obstructive Sleep Apnea as a Potential Promulgator of Atrial Fibrillation in Ischemic Stroke.

Diagnostic Scoring System for Atrial Fibrillation in Ischemic Stroke

Diagnostic Scoring System for Atrial Fibrillation in Ischemic Stroke

Abstract 12671: Left Atrial Volumes Corrected for Heart Size are Superior Echocardiographic Measures for Diagnosing Paroxysmal Atrial Fibrillation in Ischemic Stroke and Transient Ischemic Attack Patients

Introduction: The underlying cause of ischemic strokes (IS) and transient ischemic attacks (TIA) is not identified in 25% of the cases. However, asymptomatic paroxysmal atrial fibrillation (PAF) is often assumed to be the cause of the cryptogenic IS or TIA Hypothesis: The aim of this study was to examine if echocardiographic measures of LA volume (LAV) corrected for the left ventricular (LV) length (LAVMax/Min/LV length) could predict PAF in patients with IS and TIA. Methods: We retrospectively included 218 patients who after acute IS or TIA underwent a transthoracic echocardiographic examination in sinus rhythm. Patients were designated as PAF-patients if they had one or more reported incidents of AF before or after their echocardiographic examination. Results: Patients in the PAF group were significantly older (62±13 vs. 52±14 years, p&lt;0.001), had higher CHA2DS2-VASc score (3.3±1.3 vs. 3.8±1.3, p=0.042) and higher National Institutes of Health Stroke Scale (NIHSS) score (2.9±4.9 vs. 1.4±3.3, p=0.016) than patients without PAF. Besides these, no other baseline characteristics (sex, hypertension, diabetes, cholesterol) were associated with PAF. None of the conventional echocardiographic parameters (LV ejection fraction, LV volumes, E/A-ratio, E-wave deceleration time, LAVmax) were significantly associated with PAF. However, the atrial measures corrected for LV length (LAVMax/LV length and LAVMin/LV length) were significantly higher (LAVMax/LV length: 7.6±3.3 mL/cm vs. 6.5± 2.0 mL/cm, p=0.009; LAVMin/LV length: 3.7± 2.1 mL/cm vs. 2.8±1.1 mL/cm, p&lt;0.001) in patients with PAF (Figure), even after adjustment for age, gender, CHA2DS2-VASc and NIHSS scores. Conclusion: In patients with IS and TIA, measures of LA size corrected for LV length are independently associated with the presence of PAF. Applying these may yield better risk stratification for PAF-presence in patients suffering cryptogenic IS and TIA.

Abstract WP415: What Factors Determine Choice of Anticoagulant?

Introduction: Non-vitamin K antagonist Oral Anticoagulation (NOAC) agents are approved for prevention of ischemic stroke in atrial fibrillation (Afib). NOACs offer both advantages (ease of use, reduced rate of intracranial hemorrhage) and disadvantages (cost, absence of reversal agent, less clinical experience) relative to warfarin. We tested the hypothesis that the decision to prescribe a NOAC might be influenced by non-medical factors such as prescriber subspecialty or patient demographics. Methods: We performed an IRB-approved search of the Research Patient Data Registry at our major tertiary referral hospital for all Afib patients prescribed warfarin, dabigatran, rivaroxaban or apixaban between January 2013 and June 2014. We encoded data related to prescriber clinic, patient demographics (including home ZIP code as a marker of family income), intracerebral hemorrhage (ICH) and medical comorbidities. Results: Of 4,261 individuals with Afib prescribed oral anticoagulants during the specified interval, 3450 (81%) received warfarin, 442 (10.4%) rivaroxaban, 304 (7.1%) dabigatran, and 65 (1.5%) apixaban per their last prescription during the period. In univariate analyses patients prescribed NOACs were younger (71.5 ± 11.4 vs. 76.6 ± 10.5 years, p &lt; 0.001), more likely male (64.4% vs. 35.6%, p &lt; 0.005), had lower CHADS2 scores (2.17 ± 1.43 vs. 2.68 ± 1.40, p&lt;0.001) and resided in areas with higher median income ($86,384 ± 33,410 vs. $80,470 ± 30,390, p&lt;0.001). Race and prior ICH did not differ. Among 2,013 prescriptions from a defined subset of cardiology, primary care and neurology clinics, NOACs were more commonly used by cardiologists (37.1%) than neurologists (18.9%) or primary care providers (17.1%, p&lt;0.001). Multivariable analysis of this subset found that physician specialty, residential area income, age and CHADS2 score but not gender were independently associated with receiving a NOAC. Conclusions: Younger, more affluent individuals treated by a cardiologist were likeliest to receive NOACs for prevention of Afib-related stroke. The data suggest that factors other than medical characteristics might influence the decision to use NOACs.

Association of Smoking, Alcohol, and Obesity with Cardiovascular Death and Ischemic Stroke in Atrial Fibrillation: The Atherosclerosis Risk in Communities (ARIC) Study and Cardiovascular Health Study (CHS).

Atrial fibrillation (AF) is associated with an increased risk of ischemic stroke and cardiovascular (CV) death. Whether modifiable lifestyle risk factors are associated with these CV outcomes in AF is unknown. Among Atherosclerosis Risk in Communities (ARIC) study and Cardiovascular Health Study (CHS) participants with incident AF, we estimated the risk of composite endpoint of ischemic stroke or CV death associated with candidate modifiable risk factor (smoking, heavy alcohol consumption, or high body mass index [BMI]), and computed the C-statistic, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) of incorporating each factor into the CHA2DS2-VASc. Among 1222 ARIC (mean age: 63.4) and 756 CHS (mean age: 79.1) participants with incident AF, during mean follow-up of 6.9 years and 5.7 years, there were 332 and 335 composite events respectively. Compared with never smokers, current smokers had a higher incidence of the composite endpoint in ARIC [HR: 1.65 (1.21–2.26)] but not in CHS [HR: 1.05 (0.69–1.61)]. In ARIC, the addition of current smoking did not improve risk prediction over and above the CHA2DS2-VASc. No significant associations were observed with alcohol consumption or BMI with CVD outcomes in AF patients from either cohort. Smoking is associated with an increased risk of ischemic stroke or CV death in ARIC, which comprised mostly middle-aged to young-old (65–74 years), but not in CHS, which comprised mostly middle-old or oldest-old (≥75 years) adults with AF. However, addition of smoking to the CHA2DS2-VASc score did not improve risk prediction of these outcomes.

Predictive value of CHADS2 score for cardiovascular events in patients with acute coronary syndrome and documented coronary artery disease.

Background/Aims:The CHADS2 score, used to predict the risk of ischemic stroke in atrial fibrillation (AF) patients, has been reported recently to predict ischemic stroke in patients with coronary heart disease, regardless of the presence of AF. However, little data are available regarding the relationship between the CHADS2 score and cardiovascular outcomes.Methods:This was a retrospective study on 104 patients admitted for acute coronary syndrome (ACS) who underwent coronary angiography, carotid ultrasound, and transthoracic echocardiography.Results:The mean age of the subjects was 60.1 ± 12.6 years. The CHADS2 score was as follows: 0 in 46 patients (44.2%), 1 in 31 (29.8%), 2 in 18 (17.3%), and ≥ 3 in 9 patients (8.7%). The left atrial volume index (LAVi) showed a positive correlation with the CHADS2 score (20.8 ± 5.9 for 0; 23.2 ± 6.7 for 1; 26.6 ± 10.8 for 2; and 30.3 ± 8.3 mL/m2 for ≥3; p = 0.001). The average carotid total plaque area was significantly increased with CHADS2 scores ≥ 2 (4.97 ± 7.17 mm2 vs. 15.52 ± 14.61 mm2; p = 0.002). Eight patients experienced cardiovascular or cerebrovascular (CCV) events during a mean evaluation period of 662 days. A CHADS2 score ≥ 3 was related to an increase in the risk of CCV events (hazard ratio, 14.31; 95% confidence interval, 3.53 to 58.06). Furthermore, LAVi and the severity of coronary artery obstructive disease were also associated with an increased risk of CCV events.Conclusions:The CHADS2 score may be a useful prognostic tool for predicting CCV events in ACS patients with documented coronary artery disease.

Abstract 11900: Influence of Competing Risks on the Association Between Warfarin and Ischemic Stroke in Atrial Fibrillation: The Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study

Introduction: Studies examining the association between warfarin therapy and incidence of ischemic stroke in adults with atrial fibrillation (AF) have not accounted for patients who die of non-stroke causes. Hypothesis: Accounting for the competing risk of death may provide greater understanding of the “real world” impact of warfarin on stroke risk during multiyear follow-up in a large, diverse cohort of AF patients. Methods: We assessed this association in the ATRIA community-based cohort of AF patients (n=13,559; study years 1996-2003), with thromboembolic (&gt;90% ischemic stroke) events (TEE) being clinician-adjudicated. Extended Cox proportional hazards regression with time-varying warfarin exposure estimated the cause-specific hazard ratio (HR) for TEE while adjusting for stroke risk factors. Fine and Gray subdistribution regression was used to estimate this association while also accounting for competing death events. Results: Patients using warfarin were younger, more likely to have had a prior stroke, and to have known diabetes, coronary disease, and heart failure, and also had higher mean CHA2DS2VASc scores (3.68 vs. 3.22). The death rate was much higher in the non-warfarin group (8.1 deaths/100 person-years; 2637 deaths vs. 5.5 deaths/100 person-years; 1777 deaths on warfarin). The cause-specific HR indicated a large reduction in TE with warfarin use (adjusted HR: 0.57, 95% CI: 0.50-0.65). In subdistribution hazard models accounting for competing death events over the full follow-up of 6 years, this association was substantially attenuated (adjusted HR: 0.87, 95% CI: 0.77-0.99). In analyses limited to 1-year follow-up with only 648 competing death events, the results without accounting for competing risks (adjusted cause-specific HR: 0.55, 95% CI: 0.43-0.71) were similar to the results that did account for competing risks (adjusted subdistribution HR: 0.59, 95% CI: 0.46-0.75). Conclusions: By accounting for competing death events, our results reflect a more realistic estimate of the multi-year stroke prevention benefits of warfarin for patients with AF. Many old/frail individuals with AF will not live long enough to gain substantial benefit from warfarin.

Inadequate anticoagulation by Vitamin K antagonists and major adverse cardiovascular events other than stroke

I read the article by Pastori et al. [ [1] Pastori D. Pignatelli P. Saliola M. et al. Inadequate anticoagulation by Vitamin K antagonists is associated with major adverse cardiovascular events in patients with atrial fibrillation. Int. J. Cardiol. 2015; 201: 513-516 Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar ] with great interest. In their artcile, the authors reported that inadequate anticoagulation by Vitamin K Antagonists was found to be associated with Major Adverse Cardiovascular Events (MACE) in patients with atrial fibrillation, and they concluded that time in therapeutic range (TTR) was an independent predictor of MACE in patients with atrial fibrillation. It is known that inadequate anticoagulation by Vitamin K Antagonists is a strong predictor of stroke. Pastori et al. identified the predictive value of inadequate anticoagulation for MACE. However, because of some confounding factors, I would like to emphasize some important points to clarify the findings of the present article. Inadequate anticoagulation by Vitamin K Antagonists is associated with Major Adverse Cardiovascular Events in patients with atrial fibrillationInternational Journal of CardiologyVol. 201PreviewTime 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. Full-Text PDF Reply to: “Inadequate anticoagulation by vitamin K antagonists and major adverse cardiovascular events other than stroke”International Journal of CardiologyVol. 202PreviewWe have recently demonstrated that the quality of anticoagulation with vitamin K antagonists, expressed by the Time in Therapeutic Range (TTR) favourably influences the occurrence of major adverse cardiovascular events (MACE) in atrial fibrillation (AF) patients [1]. Dr. Eyuboglu raises the possibility that the use of anti-hypertensive drugs or blood pressure control may also be implicated in reducing MACE. Full-Text PDF