Association of Burden of Atrial Fibrillation With Risk of Ischemic Stroke in Adults With Paroxysmal Atrial Fibrillation: The KP-RHYTHM Study.
ABSTRACT: Importance:Atrial fibrillation is a potent risk factor for stroke, but whether the burden of atrial fibrillation in patients with paroxysmal atrial fibrillation independently influences the risk of thromboembolism remains controversial. Objective:To determine if the burden of atrial fibrillation characterized using noninvasive, continuous ambulatory monitoring is associated with the risk of ischemic stroke or arterial thromboembolism in adults with paroxysmal atrial fibrillation. Design, Setting, and Participants:This retrospective cohort study conducted from October 2011 and October 2016 at 2 large integrated health care delivery systems used an extended continuous cardiac monitoring system to identify adults who were found to have paroxysmal atrial fibrillation on 14-day continuous ambulatory electrocardiographic monitoring. Exposures:The burden of atrial fibrillation was defined as the percentage of analyzable wear time in atrial fibrillation or flutter during the up to 14-day monitoring period. Main Outcomes and Measures:Ischemic stroke and other arterial thromboembolic events occurring while patients were not taking anticoagulation were identified through November 2016 using electronic medical records and were validated by manual review. We evaluated the association of the burden of atrial fibrillation with thromboembolism while not taking anticoagulation after adjusting for the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) or CHA2DS2-VASc stroke risk scores. Results:Among 1965 adults with paroxysmal atrial fibrillation, the mean (SD) age was 69 (11.8) years, 880 (45%) were women, 496 (25%) were persons of color, the median ATRIA stroke risk score was 4 (interquartile range [IQR], 2-7), and the median CHA2DS2-VASc score was 3 (IQR, 1-4). The median burden of atrial fibrillation was 4.4% (IQR ,1.1%-17.23%). Patients with a higher burden of atrial fibrillation were less likely to be women or of Hispanic ethnicity, but had more prior cardioversion attempts compared with those who had a lower burden. After adjusting for either ATRIA or CHA2DS2-VASc stroke risk scores, the highest tertile of atrial fibrillation burden (?11.4%) was associated with a more than 3-fold higher adjusted rate of thromboembolism while not taking anticoagulants (adjusted hazard ratios, 3.13 [95% CI, 1.50-6.56] and 3.16 [95% CI, 1.51-6.62], respectively) compared with the combined lower 2 tertiles of atrial fibrillation burden. Results were consistent across demographic and clinical subgroups. Conclusions and Relevance:A greater burden of atrial fibrillation is associated with a higher risk of ischemic stroke independent of known stroke risk factors in adults with paroxysmal atrial fibrillation.
Project description:To determine if the CHA2DS2-VASc score (congestive heart failure, hypertension, age ?75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65-74 years, sex category) predicts thromboembolism and death in patients without atrial fibrillation in a population with implantable cardiac monitoring devices.A retrospective review utilizing the Rochester Epidemiology Project research infrastructure was conducted to evaluate the CHA2DS2-VASc tool as a predictor of mortality and ischemic stroke, transient ischemic attack, or systemic embolism in patients without atrial fibrillation. An implantable device was required in the inclusion criteria to discern the absence of atrial fibrillation. The study period was January 1, 2004, through March 7, 2016.The study population (N=1606) had a mean (SD) age of 69.8 (12.6) years and median follow-up of 4.8 years (range, 0-12 years; quartile 1, 2.6 years and quartile 3, 8.1 years). The number of thromboembolic and mortality events stratified by CHA2DS2-VASc score groupings of 0 to 2 (399 patients), 3 to 5 (756 patients), and 6 to 9 (451 patients) were 12 (3.0%), 109 (14.4%), and 123 (27.3%) and 22 (5.5%), 205 (27.1%), and 214 (47.4%), respectively. The CHA2DS2-VASc score predicted thromboembolism and death. The hazard ratios (HRs) for thromboembolic events for CHA2DS2-VASc scores 3 to 5 and 6 to 9 were 4.84 (95% CI, 2.66-8.80) and 10.53 (95% CI, 5.77-19.21) (reference group, scores 0-2). The HRs for death for the corresponding score categories were 4.45 (95% CI, 2.86-6.91) and 8.18 (95% CI, 5.23-12.78). The CHA2DS2-VASc score also predicted development of atrial fibrillation, for which the HRs for scores 3 to 5 and 6 to 9 were 1.51 (95% CI, 1.13-2.00) and 2.17 (95% CI, 1.60-2.95).The CHA2DS2-VASc tool predicts thromboembolic events and overall mortality in patients without atrial fibrillation who have implantable devices.
Project description:Research is conflicting whether kidney function should be incorporated in thromboembolism risk prediction. Our published data showed that the CHA2DS2-VASc score predicts thromboembolism and mortality in those without atrial fibrillation. We used the Rochester Epidemiology Project medical records system to retrospectively evaluate whether adding renal impairment (1 point) to the CHA2DS2-VASc score (-R) enhances the score's prediction of mortality, thromboembolism, and atrial fibrillation in patients without atrial fibrillation. We identified patients that had an implantable cardiac monitoring device placed from January 1, 2004 to December 31, 2013, which was defined as the start date. Follow-up was through March 7, 2016. An implantable device was required to discern the absence of atrial fibrillation. Renal impairment was defined as chronic kidney disease stage 3 or greater. The population (n?=?1,606) had a mean age of 69.8 years and median follow-up of 4.8 years. Baseline renal impairment was predictive of mortality (hazard ratio [HR] 2.06, 95% confidence interval [CI] 1.64 to 2.60, p <0.001), thromboembolism (HR 1.34, 95% CI 0.96 to 1.87, p?=?0.09), and atrial fibrillation (HR 1.31, 95% CI 0.98 to 1.74, p?=?0.07). Lower glomerular filtration rate correlated significantly with mortality. Increasing CHA2DS2-VASc-R score correlated significantly with mortality, thromboembolism, and incident atrial fibrillation. The addition of renal impairment to the CHA2DS2-VASc score improved the C-statistics for thromboembolism and survival from 0.72 to 0.73 (p?=?0.01) and 0.70 to 0.72 (p <0.001). Adding renal impairment to the CHA2DS2-VASc score improves the score's prediction of thromboembolism and mortality in a population without atrial fibrillation, although the incremental benefit appears mild.
Project description:BACKGROUND:We hypothesized that the change in stroke risk profile between baseline and follow-up may be a better predictor of ischemic stroke than the baseline stroke risk determination using the CHA2DS2-VASc score ((congestive heart failure, hypertension, age ?75 years (doubled), diabetes, stroke/transient ischemic attack/thromboembolism (doubled), vascular disease (prior myocardial infarction, peripheral artery disease, or aortic plaque), age 65-75 years, sex category (female))). METHODS:We collected information for all patients treated with atrial fibrillation (AF) in French hospitals between 2010 and 2019. We studied 608,108 patients with AF who did not have risk factors of the CHA2DS2-VASc score (except for age and sex). The predictive accuracies of baseline and follow-up CHA2DS2-VASc scores, as well as the 'Delta CHA2DS2-VASc' (i.e., change/difference between the baseline and follow-up CHA2DS2-VASc scores) for prediction of ischemic stroke were studied. RESULTS:The mean CHA2DS2-VASc score at baseline was 1.7, and increased to 2.4 during follow-up of 2.2 ± 2.4 years, (median (interquartile range: IQR) 1.2 (0.1-3.8) years), resulting in a mean Delta CHA2DS2-VASc score of 0.7. Among 20,082 patients suffering ischemic stroke during follow-up, 67.1% had a Delta CHA2DS2-VASc score ?1 while they were only 40.4% in patients without ischemic stroke. The follow-up CHA2DS2-VASc score and Delta CHA2DS2-VASc score were predictors of ischemic stroke (C-index 0.670, 95% confidence interval (CI) 0.666-0.673 and 0.637, 95%CI 0.633-0.640) and they performed better than baseline CHA2DS2-VASc score (C-index 0.612, 95%CI 0.608-0.615, p < 0.0001). CONCLUSIONS:Stroke risk was non-static, and many AF patients had ?1 new stroke risk factor(s) before ischemic stroke occurred. The follow-up CHA2DS2-VASc score and its change (i.e., 'Delta CHA2DS2-VASc') were better predictors of ischemic stroke than relying on the baseline CHA2DS2-VASc score.
Project description:The CHA2DS2-VASc score is a validated predictor of ischemic stroke in atrial fibrillation (AF) patients. However, data are limited on whether the CHA2DS2-VASc score is associated with subclinical brain structural changes or physical frailty among older AF patients. We assessed the relationship between CHA2DS2-VASc scores and brain structural changes or physical frailty in AF patients without history of stroke. Overall, 117 patients completed a comprehensive geriatric assessment for physical frailty. In brain magnetic resonance imaging sub-study (n?=?49), brain volume and white matter hyperintensity lesion burden were automatically quantified using the LESIONQUANT software program. Patients with high risk of CHA2DS2-VASc scores (? 2 in men or ? 3 in women) tended to be older and had more comorbidities, higher frailty index, and slower gait speed. Total white matter hyperintensity lesion burden was higher in those with high risk of CHA2DS2-VASc score than in those with intermediate risk (score of 1 in men or 2 in women) of CHA2DS2-VASc score (1.67 [interquartile range: 0.70-3.45] vs. 0.64 [0.19-1.44], p?=?0.036). Cognitive function was associated with brain volume, but gait speed was related with white matter hyperintensity lesion burden. In conclusion, we showed a positive relationship between CHA2DS2-VASc scores, white matter hyperintensity lesion burden, and physical frailty in older AF patients. Subclinical brain changes associated with high CHA2DS2-VASc scores may predict physical frailty risk.
Project description:<h4>Abstract</h4>The performance of scoring systems for risk stratification in patients with atrial fibrillation (AF) was not validated well in patients with stroke. The purpose of this study was to evaluate whether the risk scoring systems predict vascular outcomes in stroke patients with AF.Data were obtained from a nationwide multicenter registry for acute stroke with AF from January 1, 2013, to December 31, 2015. We investigated the predictive power of the CHADS2, CHA2DS2-VASc, ATRIA, and Essen stroke scores in stroke patients with AF. The subjects were further stratified into groups according to treatment with or without oral anticoagulants (OACs).A total of 3112 stroke with AF subjects were included. The rate of recurrent ischemic stroke and any stroke were not associated with the CHADS2, CHA2DS2-VASc, ATRIA, and Essen stroke risk scores. The risks of death and major adverse cerebrovascular and cardiovascular events (MACEs) increased sequentially with the increase of each risk score in OAC group. (the range of C-index 0.544-0.558 for recurrent ischemic stroke; 0.523-0.537 for any stroke; 0.580-0.597 for death; 0.564-0.583 for MACEs). However, in the group treated with OACs, all risk scores were significantly associated with the risk of MACEs. The C-statistics of the 4 scoring systems were 0.544 to 0.558, 0.523 to 0.537, 0.580 to 0.597, 0.564 to 0.583, respectively, for recurrent ischemic stroke, any stroke, death, and MACEs.The performance of the CHADS2, CHA2DS2-VASc, ATRIA, and Essen stroke risk scores for the prediction of recurrent stroke was unsatisfactory in stroke patients with AF whereas the performance for the prediction of recurrent stroke was not MACEs or death was good. A new risk stratification scheme that is specific for secondary stroke prevention in the AF population is needed.
Project description:With the introduction of novel oral anticoagulants (NOACs), the factors driving anticoagulant selection in atrial fibrillation (AF) in real-world practice are unclear. The goal was to examine whether and to what extent utilization has been driven by predictions of stroke risk (treatment benefit), bleeding risk (treatment harm), or prescription benefits' coverage. We extracted a cohort of patients with nonvalvular AF initiating anticoagulation from October 2010 to December 2012 from a large US database of commercial and Medicare supplement claims. Multivariable regression examined associations between ischemic stroke (CHA2DS2-VASc) and bleeding (Anticoagulation and Risk Factors in Atrial Fibrillation [ATRIA]) risk scores and benefits' generosity (proportion of costs covered by patients relative to total) with warfarin and novel oral anticoagulant (NOAC) selection and also between dabigatran and rivaroxaban. C-statistics and partial chi-square statistics were used to assess the variation explained. Of 70,498 patients initiating anticoagulation, 29.9% and 7.9% used dabigatran and rivaroxaban, respectively. Compared with warfarin, patients were less likely to receive an NOAC with high ischemic stroke risk (CHA2DS2-VASc ?2; adjusted relative risk [aRR] 0.75, 95% confidence interval [CI] 0.72 to 0.77) and high bleeding risk (ATRIA ?5; aRR 0.66, 95% CI 0.64 to 0.69) but more likely with good benefits' generosity (?20% of costs borne by patient; aRR 2.03, 95% CI 1.92 to 2.16). Prescription generosity explained almost twice the model variation as either risk score. Compared with dabigatran, patients were more likely to fill rivaroxaban with high bleeding risk (aRR 1.16, 95% CI 1.09 to 1.24). In conclusion, patients with greater bleeding and ischemic stroke risk were more likely to initiate warfarin, but generous benefits more strongly predicted NOAC usage and drove more selection.
Project description:We aimed to estimate the risk of ischemic stroke after intracranial hemorrhage in patients with atrial fibrillation.Using discharge data from all nonfederal acute care hospitals and emergency departments in California, Florida, and New York from 2005 to 2012, we identified patients at the time of a first-recorded encounter with a diagnosis of atrial fibrillation. Ischemic stroke and intracranial hemorrhage were identified using validated diagnosis codes. Kaplan-Meier survival statistics and Cox proportional hazard analyses were used to evaluate cumulative rates of ischemic stroke and the relationship between incident intracranial hemorrhage and subsequent stroke.Among 2,084,735 patients with atrial fibrillation, 50,468 (2.4%) developed intracranial hemorrhage and 89,594 (4.3%) developed ischemic stroke during a mean follow-up period of 3.2 years. The 1-year cumulative rate of stroke was 8.1% (95% CI, 7.5-8.7%) after intracerebral hemorrhage, 3.9% (95% CI, 3.5-4.3%) after subdural hemorrhage, and 2.0% (95% CI, 2.0-2.1%) in those without intracranial hemorrhage. After adjustment for the CHA2DS2-VASc score, stroke risk was elevated after both intracerebral hemorrhage (hazard ratio [HR], 2.8; 95% CI, 2.6-2.9) and subdural hemorrhage (HR, 1.6; 95% CI, 1.5-1.7). Cumulative 1-year rates of stroke ranged from 0.9% in those with subdural hemorrhage and a CHA2DS2-VASc score of 0, to 33.3% in those with intracerebral hemorrhage and a CHA2DS2-VASc score of 9.In a large, heterogeneous cohort, patients with atrial fibrillation faced a substantially heightened risk of ischemic stroke after intracranial hemorrhage. The risk was most marked in those with intracerebral hemorrhage and high CHA2DS2-VASc scores.
Project description:Purpose:Paroxysmal atrial fibrillation is often suspected as a probable cause of cryptogenic stroke. Continuous long-term ECG monitoring using insertable cardiac monitors is a clinically effective technique to screen for atrial fibrillation and superior to conventional follow-up in cryptogenic stroke. However, more studies are needed to identify factors which can help selecting patients with the highest possibility of detecting atrial fibrillation with prolonged rhythm monitoring. The clinical relevance of short-term atrial fibrillation, the need for medical intervention and the evaluation as to whether intervention results in improved clinical outcomes should be assessed. Method:The Nordic Atrial Fibrillation and Stroke Study is an international, multicentre, prospective, observational trial evaluating the occurrence of occult atrial fibrillation in cryptogenic stroke and transient ischaemic attack. Patients with cryptogenic stroke or transient ischaemic attack from the Nordic countries are included and will have the Reveal LINQ® Insertable cardiac monitor system implanted for 12 months for atrial fibrillation detection. Biomarkers which can be used as predictors for atrial fibrillation and may identify patients, who could derive the most clinical benefit from the detection of atrial fibrillation by prolonged monitoring, are being studied. Conclusion:The primary endpoint is atrial fibrillation burden within 12 months of continuous rhythm monitoring. Secondary endpoints are atrial fibrillation burden within six months, levels of biomarkers predicting atrial fibrillation, CHA2DS2-VASc score, incidence of recurrent stroke or transient ischaemic attack, use of anticoagulation and antiarrhythmic drugs, and quality of life measurements. The clinical follow-up period is 12 months. The study started in 2017 and the completion is expected at the end of 2020.
Project description:It is unclear whether oral anticoagulants are beneficial for atrial fibrillation (AF) patients with low CHA2DS2-VASc score. Age could be important in determining the risk of thromboembolism in low risk AF patients (CHA2DS2-VASc score of 1 for male or 2 for female).The Taiwan National Health Insurance Research Database (NHIRD) was used and 27,521 AF patients with CHA2DS2-VASc score of 1 (male) or 2 (female) not receiving anticoagulants were acquired as the study cohort, which were classified into three age groups: 20-49, 50-64, and 65-74 years. The clinical endpoint was the occurrence of ischemic thromboembolism within one year of follow up.During the follow-up of 0.94 ± 0.19 years, 385 (2.19%) male patients experienced ischemic thromboembolism, with annual rate of 2.32%. The annual risk ranged from 1.29%, 2.43% to 2.77% for male patients aged 20-49, 50-64 and 65-74 years respectively. Of the female patients, 218 (2.20%) experienced clinical event with annual rate of 2.32%. The annual risk increased from 1.87%, 2.28% to 2.64% for female patients aged 20-49, 50-64 and 65-74 years respectively. There was no difference in risk between the male patients aged 20-49 years with CHA2DS2-VASc score of 1 and overall male patients with CHA2DS2-VASc score of 0. (P = 0.631) The female patients aged 20-49 years with CHA2DS2-VASc score of 2 was associated with a higher risk of thromboembolic events than overall female patients with CHA2DS2-VASc score of 1 (HR = 1.93; P = 0.008).Age is important in determining the risk of thromboembolism in AF patients with single risk factor. In male patients <50 years old with CHA2DS2-VASc score of 1, the risk of ischemic thromboembolism was low. Considering the benefits and the risk of bleeding, oral anticoagulation therapy may not be favorable in these patients.
Project description:Novel oral anticoagulants (NOACs) have been shown to be at least as good as warfarin for preventing stroke or transient ischemic attack in patients with atrial fibrillation, yet diffusion of these therapies and patterns of use among atrial fibrillation patients with ischemic stroke and transient ischemic attack have not been well characterized.Using data from Get With The Guidelines-Stroke, we identified a cohort of 61 655 atrial fibrillation patients with ischemic stroke or transient ischemic attack hospitalized between October 2010 and September 2012 and discharged on warfarin or NOAC (either dabigatran or rivaroxaban). Multivariable logistic regression was used to identify factors associated with NOAC versus warfarin therapy. In our study population, warfarin was prescribed to 88.9%, dabigatran to 9.6%, and rivaroxaban to 1.5%. NOAC use increased from 0.04% to a 16% to 17% plateau during the study period, although anticoagulation rates among eligible patients did not change appreciably (93.7% versus 94.1% from first quarter 2011 to second quarter 2012), suggesting a trend of switching from warfarin to NOACs rather than increased rates of anticoagulation among eligible patients. Several bleeding risk factors and CHA2DS2-VASc scores were lower among those discharged on NOAC versus warfarin therapy (47.9% versus 40.9% with CHA2DS2-VASc ?5, P<0.001 for difference in CHA2DS2-VASc).NOACs have had modest but growing uptake over time among atrial fibrillation patients hospitalized with stroke or transient ischemic attack and are prescribed to patients with lower stroke risk compared with warfarin.