Stroke and thromboembolic event rates in atrial fibrillation according to different guideline treatment thresholds: A nationwide cohort study.
ABSTRACT: Contemporary guidelines suggest anticoagulant treatment decisions in atrial fibrillation (AF) patients to be based on risk stratification for stroke. However, guidelines do not agree on the threshold for treatment initiation. We explored the variation in thromboembolic event rates in a non-anticoagulated AF population, according to different guideline threshold and methodological approaches. AF patients between 1998 and 2014 free from anticoagulant treatment were identified. Event rates for ischemic stroke and ischemic stroke/systemic embolism were explored. The overall ischemic stroke rate was 3.20 per 100 person-years ('formal rate assessment'). For patients with a CHA2DS2-VASc score of 1 the ischemic stroke rate was 0.97 when using a 'formal rate assessment', 0.62 when using a 'conditioning on the future' approach, and 0.93 when using a 'censoring approach'. Rates for thromboembolism for the 'European treatment threshold' (CHA2DS2-VASc score of 1, males only) ranged 1.17 to 1.53. Rates for the 'U.S. treatment threshold' (CHA2DS2-VASc of 2) ranged from 1.95 to 2.33. Thromboembolic event rates differed markedly in non-anticoagulated AF patients according to the conflicting European and U.S. guideline treatment thresholds. Second, the choice of methodological approach has implications, thus we recommend using the censoring approach for event rate estimation among AF patients not on treatment.
Project description:The ABC-stroke score (age, biomarkers [N-terminal fragment B-type natriuretic peptide, high-sensitivity troponin], and clinical history [prior stroke/transient ischemic attack]) was proposed to predict stroke in atrial fibrillation (AF). This score was derived/validated in 2 clinical trial cohorts in which patients with AF were highly selected and carefully followed-up. However, the median follow-up was 1.9 years in the trial cohort; therefore, its long-term predictive performance remains uncertain. This study aimed to compare the long-term predictive performances of the ABC-stroke and CHA2DS2-VASc (cardiac failure or dysfunction, hypertension, age ?75 [doubled], diabetes mellitus, stroke [doubled]-vascular disease, age 65 to 74 years and sex category [female]) scores in a cohort of anticoagulated patients with AF.We recruited 1125 consecutive patients with AF who were stable on vitamin K antagonists and followed-up for a median of 6.5 years. ABC-stroke and CHA2DS2-VASc (cardiac failure or dysfunction, hypertension, age ?75 [doubled], diabetes mellitus, stroke [doubled]-vascular disease, age 65 to 74 years and sex category [female]) scores were calculated and compared. Median CHA2DS2-VASc and ABC-stroke scores were 4 (interquartile range 3-5) and 9.1 (interquartile range 7.3-11.3), respectively. There were 114 ischemic strokes (1.55% per year) at 6.5 years. The C-index of ABC-stroke at 3.5 years was significantly higher than CHA2DS2-VASc (0.663 versus 0.600, P=0.046), but both C-indexes were nonsignificantly different at 6.5 years. Integrated discrimination improvement showed a small improvement (<2%) in sensitivity at 3.5 and 6.5 years with ABC-stroke. For ABC-stroke, net reclassification improvement was nonsignificantly different at 3.5 years, and showed a negative reclassification at 6.5 years compared with CHA2DS2-VASc. Decision curve analyses did not show a marked improvement in clinical usefulness of the ABC-stroke score over the CHA2DS2-VASc score.In anticoagulated patients with AF followed-up over a long-term period, the novel ABC-stroke score does not offer significantly better predictive performance compared with the CHA2DS2-VASc score.
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:BACKGROUND: Atrial fibrillation (AF) is a leading cause of fatal ischemic stroke. It was recently reported that international normalized ratio (INR) levels were associated with infarct volumes. However, factors other than INR levels that affect stroke phenotypes are largely unknown. Therefore, we evaluated the determinants of stroke phenotypes (pattern and volume) among patients with AF who were not adequately anticoagulated. METHODS: We analyzed data pertaining to consecutive AF patients admitted over a 6-year period with acute MCA territory infarcts. We divided the patients according to DWI (diffusion-weighted imaging) lesion volumes and patterns, and the relationship between stroke predictors (the CHADS2 and CHA2DS2-VASc score), systemic, and local factors and each stroke phenotype were then evaluated. RESULTS: The stroke phenotypes varied among 231 patients (admission INR median 1.06, interquartile range (IQR) 1.00-1.14). Specifically, (1) the DWI lesion volumes ranged from 0.04-338.62 ml (median 11.86 ml; IQR, 3.07-44.20 ml) and (2) 46 patients had a territorial infarct pattern, 118 had a lobar/deep pattern and 67 had a small scattered pattern. Multivariate testing revealed that the CHADS2 and CHA2DS2-VASc score were not related to either stroke phenotype. Additionally, the prior use of antiplatelet agents was not related to the stroke phenotypes. Congestive heart failure and diastolic dysfunction were not associated with stroke phenotypes. CONCLUSIONS: The results of this study indicated that the determinants of stroke phenotypes were different from the predictors (i.e., CHADS2 and CHA2DS2-VASc score) of stroke in patients with AF.
Project description:Background:We aimed to determine the relative frequency of affected cerebrovascular territories in patients with atrial fibrillation (AF) suffering an ischemic stroke. Methods:Altogether, 1,976 patients who suffered their first-ever ischemic stroke during 2003-2012 and were diagnosed with AF either before or within 30 days after the event were included in this retrospective multicenter cohort study. Strokes were classified radiographically to be located either within the anterior or the posterior cerebrovascular territory, and the effect of the CHA2DS2-VASc score, oral anticoagulant (OAC) use, and timing of AF diagnosis on lesion localization was determined. Results:The median age of the patients was 78.4 (interquartile range: 71.7-84.2) years, 1,137 (57.5%) of them were women, their mean CHA2DS2-VASc score was 3.5 (95% confidence interval: 3.4-3.5), 656 (33.2%) were receiving OAC drugs, and altogether, 1,450 (73%) had a previous AF diagnosis. The localization of ischemic lesions between the anterior and the posterior cerebrovascular territories was not affected by the timing of AF diagnosis (p = 0.46), use of OACs (p = 0.70), or the CHA2DS2-VASc score (p = 0.10). Within the anterior territory, altogether 774 strokes (53.2%) were located in the left hemisphere and 3 (0.2%) were bilateral. The timing of AF diagnosis (p = 0.84), use of OACs (p = 0.90), or the CHA2DS2-VASc score (p = 0.21) did not affect the location of the ischemic lesion between the hemispheres. Conclusions:The timing of AF diagnosis, use of OAC drugs, or the CHA2DS2-VASc score did not affect the distribution of ischemic strokes. Anterior territory strokes were slightly more often located within the left hemisphere.
Project description:BACKGROUND:In people with atrial fibrillation (AF), periods of sinus rhythm present an opportunity to detect prothrombotic atrial remodeling through measurement of P-wave indices (PWIs)-prolonged P-wave duration, abnormal P-wave axis, advanced interatrial block, and abnormal P-wave terminal force in lead V1. We hypothesized that the addition of PWIs to the CHA2DS2-VASc score would improve its ability to predict AF-related ischemic stroke. METHODS:We included 2229 participants from the ARIC study (Atherosclerosis Risk in Communities) and 700 participants from MESA (Multi-Ethnic Study of Atherosclerosis) with incident AF who were not on anticoagulants within 1 year of AF diagnosis. PWIs were obtained from study visit ECGs before development of AF. AF was ascertained using study visit ECGs and hospital records. Ischemic stroke cases were based on physician adjudication of hospital records. We used Cox proportional hazards models to estimate hazard ratios and 95% CIs of PWIs for ischemic stroke. Improvement in 1-year stroke prediction was assessed by C-statistic, categorical net reclassification improvement, and relative integrated discrimination improvement. RESULTS:Abnormal P-wave axis was the only PWI associated with increased ischemic stroke risk (hazard ratio, 1.84; 95% CI, 1.33-2.55) independent of CHA2DS2-VASc variables, and that resulted in meaningful improvement in stroke prediction. The ? estimate was approximately twice that of the CHA2DS2-VASc variables, and thus abnormal P-wave axis was assigned 2 points to create the P2-CHA2DS2-VASc score. This improved the C-statistic (95% CI) from 0.60 (0.51-0.69) to 0.67 (0.60-0.75) in ARIC and 0.68 (0.52-0.84) to 0.75 (0.60-0.91) in MESA (validation cohort). In ARIC and MESA, the categorical net reclassification improvements (95% CI) were 0.25 (0.13-0.39) and 0.51 (0.18-0.86), respectively, and the relative integrated discrimination improvement (95% CI) were 1.19 (0.96-1.44) and 0.82 (0.36-1.39), respectively. CONCLUSIONS:Abnormal P-wave axis-an ECG correlate of left atrial abnormality- improves ischemic stroke prediction in AF. Compared with CHA2DS2-VASc, the P2-CHA2DS2-VASc is a better prediction tool for AF-related ischemic stroke.
Project description:Recent hospital-based cohort studies found the CHA2DS2-VASc score to be associated with ischemic stroke in individuals without atrial fibrillation (AF). Our aim was to determine the distribution of embolic and thrombotic strokes and association with the CHA2DS2-VASc score, among community-dwelling individuals without AF. We included participants from the Atherosclerosis Risk in Communities (ARIC) Study who attended visit 4 (1996 to 1998) and had no previous AF, stroke, or anticoagulant use (n?=?10,671). During follow-up through 2008, incident AF cases (n?=?760) and participants who started warfarin were censored. Incident AF was ascertained from study electrocardiograms and hospital discharge diagnosis codes, and stroke was physician-adjudicated. After 10 years of follow-up, 280 ischemic strokes were identified, of which 146 were thrombotic and 57 embolic. The hazard ratios (95% confidence intervals [CI]) for thrombotic stroke were 1 (reference), 1.71 (1.13 to 2.59), 2.92 (1.91 to 4.45), 3.22 (1.70 to 6.11), and 1.25 (0.17 to 9.09), with CHA2DS2-VASc scores of 0 to 1, 2, 3, 4, and ?5, respectively. The hazard ratios (95% CI) for embolic stroke were 1 (ref), 4.91 (2.10 to 11.5), 7.07 (2.93 to 17.0), 14.8 (5.50 to 39.6), and 15.2 (3.16 to 73.3), with CHA2DS2-VASc scores of 0 to 1, 2, 3, 4, and ?5, respectively. A receiver-operating characteristic model had a C-statistic of 0.65 for ischemic stroke, 0.61 for thrombotic stroke, and 0.71 for embolic stroke. In conclusion, in community-dwelling individuals without AF, the CHA2DS2-VASc score can assess ischemic stroke risk and has good discriminatory capacity for embolic stroke.
Project description: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.
Project description:Importance:Current guidelines support treating atrial fibrillation (AF) and atrial flutter (AFL) as equivalent risk factors for ischemic stroke stratified by CHA2DS2-VASc scores, recommending anticoagulation therapy for patients with a CHA2DS2-VASc score of 2 or higher, but some studies found differences in clinical outcomes. Objective:To investigate differences in clinical outcomes among AF, AFL, and matched control cohorts. Design, Setting, and Participants:This nationwide cohort study analyzed data from the Taiwan National Health Insurance Research Database from January 1, 2001, through December 31, 2012. Follow-up and data analysis ended December 31, 2012. A total of 219 416 age- and sex-matched individuals participated in the study. Clinical outcomes were compared after stratification by CHA2DS2-VASc score (possible score range, 0-9; higher scores indicate greater risk of ischemic stroke). Main Outcomes and Measures:Ischemic stroke, heart failure hospitalization, and all-cause mortality among the AF, AFL, and matched control cohorts were analyzed using Cox proportional hazards regression. Results:This study comprised 188?811 patients in the AF cohort (mean [SD] age, 73.8 [13.4] years; 104 703 [55.5%] male), 6121 patients in the AFL cohort (mean [SD] age, 67.7 [15.8] years; 3735 [61.0%] male), and 24?484 patients in the matched control cohort (mean [SD] age, 67.3 [15.6] years; 14 940 [61.0%] male). The patients with AF were older, were more predominantly female, and had higher CHA2DS2-VASc scores than the patients with AFL and the control participants. After stratification by CHA2DS2-VASc score, the incidence densities (IDs; events per 100 person-years) of ischemic stroke (AF cohort: ID, 3.08; 95% CI, 3.03-3.13; AFL cohort: ID, 1.45; 95% CI, 1.28-1.62; controls: ID, 0.97; 95% CI, 0.92-1.03), heart failure hospitalization (AF cohort: ID, 3.39; 95% CI, 3.34-3.44; AFL cohort: ID, 1.57; 95% CI, 1.39-1.74; controls: ID, 0.32; 95% CI, 0.29-0.35), and all-cause mortality (AF cohort: ID, 17.8; 95% CI, 17.7-17.9; AFL cohort: ID, 13.9; 95% CI, 13.4-14.4; controls: ID, 4.2; 95% CI, 4.1-4.4) were significantly higher in the AF cohort than in the matched control cohort. For the AFL cohort vs the matched control cohort, the incidences of heart failure hospitalization and all-cause mortality were significantly higher across all levels, but the incidence of ischemic stroke was only significantly higher at CHA2DS2-VASc scores of 5 to 9. For the AF cohort vs the AFL cohort, the incidences of ischemic stroke and heart failure hospitalization were significantly higher at a CHA2DS2-VASc score of 1 or higher, but the incidence of all-cause mortality was significantly higher only at CHA2DS2-VASc scores of 1 to 3. Conclusions and Relevance:This study found different clinical outcomes between patients with AFL and AF and those without AF and AFL. The current recommended level of the CHA2DS2-VASc score in preventing ischemic stroke in patients with AFL should be reevaluated.
Project description:BACKGROUND:The CHA2DS2-VASc score is used to assess risk of mortality as well as to stratify risk of stroke in patients with atrial fibrillation (AF). This study evaluated whether CHA2DS2-VASc score was predictive of 1 and 2 year risks of stroke and death in Asian patients with heart failure (HF). METHODS:Patients hospitalized for HF were enrolled in the Korean Acute Heart Failure (KorAHF) registry, a prospective observational multicenter cohort study, between March 2011 and February 2014. Patients with a history of cancer before hospitalization for HF were excluded. The discriminatory properties of the CHA2DS2-VASc score were quantified using C-statistics. RESULTS:The study included 5158 patients with HF, 2091 with and 3067 without AF. Rates of stroke in these two groups were 4.5 and 2.8%, respectively, after 1 year, and 5.5 and 3.4%, respectively, after 2 years. Each 1-point increase in CHA2DS2-VASc score was associated with significantly increased risks of stroke and all-cause death in HF patients with and without AF (p-value < 0.05). The C-statistics of the CHA2DS2-VASc score for all-cause death in patients with and without AF were 0.600 and 0.630, respectively, at 1 year and 0.626 and 0.635, respectively, at 2 years. The C-statistics for stroke ranged from 0.593 to 0.639. CONCLUSIONS:Among patients with incident HF with and without AF, CHA2DS2-VASc score was significantly associated with the risks of stroke and death. However, CHA2DS2-VASc score was only a modest predictor of stroke and death, indicating the need for studies evaluating modified CHA2DS2-VASc scores. The majority of strokes occurred relatively shortly after hospitalization for HF and that mortality rates in patients with HF remain high. Thus, early treatment after HF to prevent stroke is essential.
Project description:Ischemic stroke following coronary revascularization procedures remains one of the most potentially devastating complications. CHA2DS2-VASc score has been widely used for stroke risk stratification in AF patients. The aim of this nationwide study was to examine the association between the CHA2DS2-VASc score and ischemic stroke following coronary revascularization procedures. We identified patients undergoing coronary revascularization procedures, coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI), using the electronic Hospitalization Summary Reports. Logistic regression models were applied to evaluate the association of CHA2DS2-VASc score with the risk of post-procedural ischemic stroke. We identified 54,714 patients undergoing CABG and 263,063 patients undergoing PCI from 2013 to 2015. The CHA2DS2-VASc score had a positive graded association with the risk of post-procedural ischemic stroke in both CABG and PCI (P for trend <0.001). The adjusted risk of post-procedural ischemic stroke increased by an estimated 122.4% (odds ratio [OR], 2.22; 95% confidence interval [CI], 2.11-2.35) and 34.7% (OR, 1.35; 95% CI, 1.31-1.39) for each additional 1 point in the CHA2DS2-VASc score in CABG and PCI, respectively. In conclusion, these findings suggested that CHA2DS2-VASc score was an independent predictor of the development of post-procedural ischemic stroke in patients undergoing CABG and PCI.