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Importance: Use of race-specific risk prediction in clinical medicine is being questioned. Yet, the most commonly used prediction tool for atherosclerotic cardiovascular disease (ASCVD)-pooled cohort risk equations (PCEs)-uses race stratification., Objective: To quantify the incremental value of race-specific PCEs and determine whether adding social determinants of health (SDOH) instead of race improves model performance., Design, Setting, and Participants: Included in this analysis were participants from the biracial Reasons for Geographic and Racial Differences in Stroke (REGARDS) prospective cohort study. Participants were aged 45 to 79 years, without ASCVD, and with low-density lipoprotein cholesterol level of 70 to 189 mg/dL or non-high-density lipoprotein cholesterol level of 100 to 219 mg/dL at baseline during the period of 2003 to 2007. Participants were followed up to 10 years for incident ASCVD, including myocardial infarction, coronary heart disease death, and fatal and nonfatal stroke. Study data were analyzed from July 2022 to February 2023., Main Outcome/measures: Discrimination (C statistic, Net Reclassification Index [NRI]), and calibration (plots, Nam D'Agostino test statistic comparing observed to predicted events) were assessed for the original PCE, then for a set of best-fit, race-stratified equations including the same variables as in the PCE (model C), best-fit equations without race stratification (model D), and best-fit equations without race stratification but including SDOH as covariates (model E)., Results: This study included 11 638 participants (mean [SD] age, 61.8 [8.3] years; 6764 female [58.1%]) from the REGARDS cohort. Across all strata (Black female, Black male, White female, and White male participants), C statistics did not change substantively compared with model C (Black female, 0.71; 95% CI, 0.68-0.75; Black male, 0.68; 95% CI, 0.64-0.73; White female, 0.77; 95% CI, 0.74-0.81; White male, 0.68; 95% CI, 0.64-0.71), in model D (Black female, 0.71; 95% CI, 0.67-0.75; Black male, 0.68; 95% CI, 0.63-0.72; White female, 0.76; 95% CI, 0.73-0.80; White male, 0.68; 95% CI, 0.65-0.71), or in model E (Black female, 0.72; 95% CI, 0.68-0.76; Black male, 0.68; 95% CI, 0.64-0.72; White female, 0.77; 95% CI, 0.74-0.80; White male, 0.68; 95% CI, 0.65-0.71). Comparing model D with E using the NRI showed a net percentage decline in the correct assignment to higher risk for male but not female individuals. The Nam D'Agostino test was not significant for all race-sex strata in each model series, indicating good calibration in all groups., Conclusions: Results of this cohort study suggest that PCE performed well overall but had poorer performance in both BM and WM participants compared with female participants regardless of race in the REGARDS cohort. Removal of race or the addition of SDOH did not improve model performance in any subgroup.

Background: An unmet need exists to reliably predict the risk of intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF) treated with oral anticoagulants (OACs)., Hypothesis: An externally validated model improves ICH risk stratification., Methods: Independent factors associated with ICH were identified by Cox proportional hazard modeling, using pooled data from the GARFIELD-AF (Global Anticoagulant Registry in the FIELD-Atrial Fibrillation) and ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registries. A predictive model was developed and validated by bootstrap sampling and by independent data from the Danish National Patient Register., Results: In the combined training data set, 284 of 53 878 anticoagulated patients had ICH over a 2-year period (0.31 per 100 person-years; 95% confidence interval [CI]: 0.28-0.35). Independent predictors of ICH included: older age, prior stroke or transient ischemic attack, concomitant antiplatelet (AP) use, and moderate-to-severe chronic kidney disease (CKD). Vitamin K antagonists (VKAs) were associated with a significantly higher risk of ICH compared with non-VKA oral anticoagulants (NOACs) (adjusted hazard ratio: 1.61; 95% CI: 1.25-2.08; p = .0002). The ability of the model to discriminate individuals in the training set with and without ICH was fair (optimism-corrected C-statistic: 0.68; 95% CI: 0.65-0.71) and outperformed three previously published methods. Calibration between predicted and observed ICH probabilities was good in both training and validation data sets., Conclusions: Age, prior ischemic events, concomitant AP therapy, and CKD were important risk factors for ICH in anticoagulated AF patients. Moreover, ICH was more frequent in patients receiving VKA compared to NOAC. The new validated model is a step toward mitigating this potentially lethal complication., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Importance: Professional societies and the Centers for Medicare & Medicaid Services suggest volume thresholds to ensure quality in transcatheter aortic valve implantation (TAVI)., Objective: To model the association of volume thresholds vs spoke-and-hub implementation of outcome thresholds with TAVI outcomes and geographic access., Design, Setting, and Participants: This cohort study included patients who enrolled in the US Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy registry. Site volume and outcomes were determined from a baseline cohort of adults undergoing TAVI between July 1, 2017, and June 30, 2020., Exposures: Within each hospital referral region, TAVI sites were categorized by volume (<50 or ≥50 TAVIs per year) and separately by risk-adjusted outcome on the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy 30-day TAVI composite during the baseline period (July 2017 to June 2020). Outcomes of patients undergoing TAVIs from July 1, 2020, to March 31, 2022, were then modeled as though the patients had been treated at (1) the nearest higher volume (≥50 TAVIs per year) or (2) the best outcome site within the hospital referral region., Main Outcomes and Measures: The primary outcome was the absolute difference in events between the adjusted observed and modeled 30-day composite of death, stroke, major bleeding, stage III acute kidney injury, and paravalvular leak. Data are presented as the number of events reduced under the above scenarios with 95% bayesian credible intervals (CrIs) and median (IQR) driving distance., Results: The overall cohort included 166 248 patients with a mean (SD) age of 79.5 (8.6) years; 74 699 (47.3%) were female and 6657 (4.2%) were Black; 158 025 (95%) were treated in higher-volume sites (≥50 TAVIs) and 75 088 (45%) were treated in best-outcome sites. Modeling a volume threshold, there was no significant reduction in estimated adverse events (-34; 95% CrI, -75 to 8), while the median (IQR) driving time from the existing site to the alternate site was 22 (15-66) minutes. Transitioning care to the best outcome site in a hospital referral region resulted in an estimated 1261 fewer adverse outcomes (95% CrI, 1013-1500), while the median (IQR) driving time from the original site to the best site was 23 (15-41) minutes. Directionally similar findings were observed for Black individuals, Hispanic individuals, and individuals from rural areas., Conclusions and Relevance: In this study, compared with the current system of care, a modeled outcome-based spoke-and-hub paradigm of TAVI care improved national outcomes to a greater extent than a simulated volume threshold, at the cost of increased driving time. To improve quality while maintaining geographic access, efforts should focus on reducing site variation in outcomes.

Background Among patients with nonvalvular atrial fibrillation (AF) and an elevated stroke risk, guidelines recommend direct oral anticoagulants (DOACs) over warfarin for stroke prevention. Changes in DOAC use over the past decade have not been well described. Methods and Results We evaluated trends in use of DOACs and warfarin from 2011 to 2020 among adults with AF and a CHA 2 DS 2 -VASc score ≥2 based on electronic health record data from 88 health systems in the United States contributing to Cerner Real World Data. The use of DOACs and warfarin was described over time, by age, sex, race, and ethnicity, and at the health-system level. We identified 436 864 patients with AF at risk for stroke (median age, 78 years; 52.1% men). From 2011 to 2020, overall anticoagulation rates increased from 56.3% to 64.7%, as DOAC use increased steadily (from 4.7% to 47.9%), while warfarin use declined (from 52.4% to 17.7%). DOAC uptake was similar across age, sex, and race and ethnicity groups but varied by health system. In 2020, the median health-system-level proportion of patients with AF on a DOAC was 49% (interquartile range, 40%-54%). Conclusions Over the past decade, anticoagulation rates for patients with AF have increased modestly as DOACs largely replaced warfarin, though significant gaps remain: One in 3 high-risk patients with AF is not on any anticoagulant. While DOAC adoption was generally consistent across major demographic groups, use between health systems remained highly variable, suggesting that provider and system factors influence DOAC uptake use more than patient-level factors.

Background: Among individuals with atherosclerotic cardiovascular disease (ASCVD), type 2 diabetes mellitus (T2DM) is common and confers increased risk for morbidity and mortality. Differentiating risk is key to optimize efficiency of treatment selection. Our objective was to develop and validate a model to predict risk of major adverse cardiovascular events (MACE) comprising the first event of cardiovascular death, myocardial infarction (MI), or stroke for individuals with both T2DM and ASCVD., Methods: Using data from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), we used Cox proportional hazards models to predict MACE among participants with T2DM and ASCVD. All baseline covariates collected in the trial were considered for inclusion, although some were excluded immediately because of large missingness or collinearity. A full model was developed using stepwise selection in each of 25 imputed datasets, and comprised candidate variables selected in 20 of the 25 datasets. A parsimonious model with a maximum of 10 degrees of freedom was created using Cox models with least absolute shrinkage and selection operator (LASSO), where the adjusted R-square was used as criterion for selection. The model was then externally validated among a cohort of participants with similar criteria in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial. Discrimination of both models was assessed using Harrell's C-index and model calibration by the Greenwood-Nam-D'Agostino statistic based on 4-year event rates., Results: Overall, 1491 (10.2%) of 14,671 participants in TECOS and 130 (9.3%) in the ACCORD validation cohort (n = 1404) had MACE over 3 years' median follow-up. The final model included 9 characteristics (prior stroke, age, chronic kidney disease, prior MI, sex, heart failure, insulin use, atrial fibrillation, and microvascular complications). The model had moderate discrimination in both the internal and external validation samples (C-index = 0.65 and 0.61, respectively). The model was well calibrated across the risk spectrum-from a cumulative MACE rate of 6% at 4 years in the lowest risk quintile to 26% in the highest risk quintile., Conclusion: Among patients with T2DM and prevalent ASCVD, this 9-factor risk model can quantify the risk of future ASCVD complications and inform decision making for treatments and intensity., (© 2022. The Author(s).)

Importance: After the publication of the CHANCE (Clopidogrel in High Risk Patients With Acute Nondisabling Cerebrovascular Events) and POINT (Platelet-Oriented Inhibition in New Transient Ischemic Attack and Minor Ischemic Stroke) clinical trials, the American Heart Association/American Stroke Association (AHA/ASA) issued a new class 1, level of evidence A, recommendation for dual antiplatelet therapy (DAPT; aspirin plus clopidogrel) for secondary prevention in patients with minor ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score ≤3). The extent to which variations in DAPT prescribing patterns remain and the extent to which practice patterns in the US are consistent with evidence-based guidelines are unknown., Objective: To evaluate the discharge DAPT prescribing patterns after publication of the new AHA/ASA guidelines and assess the extent of hospital-level variation in the use of DAPT for secondary prevention in patients with minor stroke (NIHSS score ≤3), as indicated by guidelines, and in patients with nonminor stroke (NIHSS score >3), for whom the risks and benefits of DAPT have not been fully established., Design, Setting, and Participants: This multicenter retrospective cohort study involved 132 817 patients from 1890 hospitals participating in the AHA/ASA Get With The Guidelines-Stroke program. Patients who were hospitalized for acute ischemic stroke and prescribed antiplatelet therapy at discharge between October 1, 2019, and June 30, 2020, were included., Exposures: Minor ischemic stroke (NIHSS score ≤3) vs nonminor ischemic stroke (NIHSS score >3)., Main Outcomes and Measures: The primary outcome was DAPT prescription at discharge. The extent to which variations in DAPT use were explained at the hospital level was assessed by calculating the median odds ratio (OR), which was derived using multivariable logistic regression analysis and compared the likelihood that 2 patients with identical clinical features admitted to 2 randomly selected hospitals (1 with higher propensity and 1 with lower propensity for DAPT use) would receive DAPT at discharge. Associations between hospital-level DAPT use among patients with minor vs nonminor stroke were evaluated using Pearson ρ correlation coefficients., Results: Among 132 817 patients (median [IQR] age, 68 [59-78] years; 68 768 men [51.8%]), 4282 (3.2%) were Asian, 11 254 (8.5%) were Hispanic, 27 221 (20.5%) were non-Hispanic Black, 84 468 (63.6%) were non-Hispanic White, and 5592 (4.2%) were of other races and/or ethnicities (including American Indian or Alaska Native, Native Hawaiian or Pacific Islander, and unable to determine). Overall, 86 551 patients (65.2%) presented with minor ischemic stroke, and 46 266 patients (34.8%) presented with nonminor ischemic stroke. After the 2019 AHA/ASA guideline updates, 40 661 patients (47.0%) with minor stroke (NIHSS median [IQR] score, 1 [0-2]) and 19 703 patients (42.6%) with nonminor stroke (NIHSS median [IQR] score, 6 [5-9]) received DAPT at discharge. Despite guideline recommendations, 45 890 patients (53.0%) with minor stroke did not receive DAPT. After accounting for patient characteristics, substantial hospital-level variations were found in the use of DAPT in those with minor stroke (median [IQR] hospital-level DAPT prescription rate, 44.8% [33.7%-57.7%]; range, 0%-91.7%; median OR, 2.03 [95% CI, 1.97-2.09]) when comparing 2 patients with identical risk factors discharged from 2 randomly selected hospitals, 1 with higher propensity and 1 with lower propensity for DAPT use. The use of DAPT in patients with nonminor stroke also varied significantly (median [IQR] hospital-level DAPT prescription rate, 41.4% [30.0%-53.8%]; range, 0%-100%; median OR, 1.90 [95% CI, 1.83-1.97]). Overall, hospitals that were more likely to prescribe DAPT for minor strokes were also more likely to prescribe DAPT for nonminor strokes (Pearson ρ = 0.72; P < .001)., Conclusions and Relevance: This cohort study found that despite updated AHA/ASA guidelines, more than 50% of patients with minor acute ischemic stroke did not receive DAPT at discharge. In contrast, more than 40% of patients with nonminor stroke received DAPT despite lack of evidence in this setting. These findings suggest that enhancing adherence to evidence-based DAPT practice guidelines may be a target for quality improvement in the treatment of patients with ischemic stroke.

Background: Cardioversion is common among patients with atrial fibrillation (AF). We hypothesised that novel oral anticoagulants (NOAC) used in clinical practice resulted in similar rates of stroke compared with vitamin K antagonists (VKA) for cardioversion., Methods: Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II, patients with AF who had a cardioversion, follow-up data and an AF diagnosis within 6 months of enrolment were identified retrospectively. Clinical outcomes were compared for patients receiving a NOAC or VKA for 1 year following cardioversion., Results: Among 13 004 patients with AF, 2260 (17%) underwent cardioversion. 1613 met the inclusion criteria for this analysis. At the time of cardioversion, 283 (17.5%) were receiving a VKA and 1330 (82.5%) a NOAC. A transoesophageal echocardiogram (TOE) was performed in 403 (25%) cardioversions. The incidence of stroke/transient ischaemic attack (TIA) at 30 days was the same for patients having (3.04 per 100 patient-years) or not having (3.04 per 100 patient-years) a TOE (p=0.99). There were no differences in the incidence of death (HR 1.19, 95% CI 0.62 to 2.28, p=0.61), cardiovascular hospitalisation (HR 1.02, 95% CI 0.76 to 1.35, p=0.91), stroke/TIA (HR 1.18, 95% CI 0.30 to 4.74, p=0.81) or bleeding-related hospitalisation (HR 1.29, 95% CI 0.66 to 2.52, p=0.45) at 1 year for patients treated with either a NOAC or VKA., Conclusions: Cardioversion was a low-risk procedure for patients treated with NOAC, and there were statistically similar rates of stroke/TIA 30 days after cardioversion as for patients treated with VKA. There were no statically significant differences in death, stroke/TIA or major bleeding at 1 year among patients treated with NOAC compared with VKA after cardioversion., Competing Interests: Competing interests: BJG: member of a Data Safety Monitoring Board for Mount Sinai St Luke's, Boston Scientific, Teva Pharmaceutical Industries, St Jude Medical, Janssen Research & Development, Baxter Healthcare and Cardiovascular Research Foundation; consultant/Advisory Board for Janssen Scientific Affairs, Cipla, Armetheon and Medtronic. MDE: consultant/Advisory Board and grant support from Boehringer Ingelheim, Diachi Sanko, Pfizer, Bristol Myers Squibb and Janssen Scientific Affairs. PRK: consultant for Johnson and Johnson. JAR: research grant from Janssen Pharmaceuticals; research support from Boehringer Ingelheim Pharmaceuticals and GlaxoSmithKline; consultancies with Sanofi, Gilead Sciences, CV Therapeutics, GlaxoSmithKline, Merck & Co, Cardiome Pharma, Boehringer Ingelheim Pharmaceuticals and Medtronic; speakers bureau income from Sanofi and Boehringer Ingelheim Pharmaceuticals. GN: research grant from Janssen; consultant/Advisory Board for Janssen and Daiichi Sankyo. KWM: financial disclosures can be viewed at http://med.stanford.edu/profiles/kenneth-mahaffey. DES: consultant/Advisory Board for Boehringer Ingelheim, Bristol Myers Squibb, Merck, Johnson and Johnson, Pfizer and Medtronic; research grants from Boehringer Ingelheim and Bristol Myers Squibb. JF: consultant/Advisory Board for Janssen Scientific., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

We sought to determine if the absence of hypertension in older adults can be used to identify those at lower risk of atherosclerotic cardiovascular disease (ASCVD). We identified participants ≥75 years old free of cardiovascular disease (CVD) in the National Institutes of Health Pooled Cohorts with and without hypertension. We assessed the association between systolic blood pressure (BP), diastolic BP, and cardiovascular events using multivariable modeling. The association between predicted ASCVD risk and observed events was compared. Of 2,667 adults aged ≥75 years, 67.9% had hypertension. Lower systolic BP correlated with lower CVD event rates. ASCVD predicted risk score and systolic BP were both independently associated with ASCVD event rates. Among adults with similar ASCVD predicted risk estimates, those without (vs with) hypertension had lower observed event rates across the predicted risk spectrum. The absence of hypertension may help refine the risk stratification of older adults, particularly those with intermediate predicted risk., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aims: Prediction models for outcomes in atrial fibrillation (AF) are used to guide treatment. While regression models have been the analytic standard for prediction modelling, machine learning (ML) has been promoted as a potentially superior methodology. We compared the performance of ML and regression models in predicting outcomes in AF patients., Methods and Results: The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) and Global Anticoagulant Registry in the FIELD (GARFIELD-AF) are population-based registries that include 74 792 AF patients. Models were generated from potential predictors using stepwise logistic regression (STEP), random forests (RF), gradient boosting (GB), and two neural networks (NNs). Discriminatory power was highest for death [STEP area under the curve (AUC) = 0.80 in ORBIT-AF, 0.75 in GARFIELD-AF] and lowest for stroke in all models (STEP AUC = 0.67 in ORBIT-AF, 0.66 in GARFIELD-AF). The discriminatory power of the ML models was similar or lower than the STEP models for most outcomes. The GB model had a higher AUC than STEP for death in GARFIELD-AF (0.76 vs. 0.75), but only nominally, and both performed similarly in ORBIT-AF. The multilayer NN had the lowest discriminatory power for all outcomes. The calibration of the STEP modelswere more aligned with the observed events for all outcomes. In the cross-registry models, the discriminatory power of the ML models was similar or lower than the STEP for most cases., Conclusion: When developed from two large, community-based AF registries, ML techniques did not improve prediction modelling of death, major bleeding, or stroke., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

The aim of this study was to quantify time in therapeutic range (TTR) before and after a temporary interruption of warfarin due to an intervention in the Outcomes Registry for Better Informed Treatment of atrial fibrillation (AF). AF patients on warfarin who had a temporary interruption followed by resumption were identified. A nonparametric method for estimating survival functions for interval censored data was used to examine the first therapeutic International Normalized Ratio (INR) after interruption. TTR was compared using Wilcoxon signed rank test. Cox proportional hazards model was used to investigate the association between TTR in the first 3 months after interruption and subsequent outcomes at 3 to 9 months. Of 9,749 AF patients, 71% were on warfarin. Over a median (IQR) follow-up of 2.6 (1.8 to 3.1) y, 33% of patients had a total of 3,022 temporary interruptions. The first therapeutic INR was recorded within 1 week in 35.0% (95% confidence interval 32.6% to 37.4%), 2 weeks in 54.6% (52.2% to 57.0%), 30 days in 70.0% (67.9% to 72.1%) and 90 days in 91.3% (90.0% to 92.5%) of patients. Compared with pre-interruption, TTR 3 months after interruption was significantly lower (61.1% [36.6% to 85.0%] vs 67.6% [50.0% to 81.3%], p <0.0001). A 10 unit increment in the TTR in the first 3 months after interruption was associated with a lower risk of major bleeding [Hazard ratio 0.91 (0.85 to 0.97), p = 0.005]. This association was noted in patients who received bridging anticoagulation, but not in those who did not. In conclusion, temporary interruption of warfarin is common, and nearly half of these patients had subtherapeutic INR after 2 weeks. Lower TTR in the first 3 months after interruption was associated with higher incidence of major bleeding in patients who received bridging anticoagulation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aims: To determine the extent of shared decision-making (SDM), during selection of oral anticoagulant (OAC) and rhythm control treatments, in patients with newly diagnosed atrial fibrillation (AF)., Methods and Results: We evaluated survey data from 1006 patients with new-onset AF enrolled at 56 US sites participating in the SATELLITE substudy of the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT II). Patients completed surveys at enrolment and at 6-month follow-up. Patients were asked about who made their AF treatment decisions. Shared decision-making was classified as one that the patient felt was an autonomous decision or a shared decision with their healthcare provider (HCP). Approximately half of patients reported that their OAC treatment decisions were made entirely by their HCP. Compared with those reporting no SDM, patients reporting SDM for OAC were more often female (47.2% vs. 38.4%), while patients reporting SDM for rhythm control were more often male (62.2% vs. 57.6%). The most important factors cited by patients during decision-making for OAC were reducing stroke and bleeding risk, and their HCP's recommendations. After adjustment, patients with self-reported understanding of OAC, and rhythm control options, had higher odds of having participated in SDM [odds ratio (OR) 2.54, confidence interval (CI): 1.75-3.68 and OR 2.36, CI: 1.50-3.71, both P ≤ 0.001, respectively]., Conclusion: Shared decision-making is not widely implemented in contemporary AF practice. Patient understanding about available therapeutic options is associated with a more than a two-fold higher likelihood of SDM, and may be a potential target for future interventions., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

While oral anticoagulation is a cornerstone of stroke prevention therapy in atrial fibrillation (AF), few studies have evaluated comparative discontinuation rates in clinical practice. The objective of this study is to evaluate discontinuation rates among patients on warfarin and direct oral anticoagulants (DOACs) in clinical practice., Methods: The ORBIT-AF II Registry enrolled 10,005 total AF patients with a CHA 2 DS 2 VASc score of ≥2 on warfarin or DOACs from 235 clinical practices across the US from February 13, 2013 and July 12, 2017. Descriptive statistics and multivariable Cox regression modeling were used to describe baseline characteristics and predictors of discontinuation. Unadjusted and adjusted discontinuation rates and 95% confidence intervals (CI) were calculated using Cox proportional hazards models and propensity score adjustment, respectively., Results: At baseline, 16.4% (N = 1642/10,005) were treated with warfarin, 83.6% (N = 8363/10,005) with DOACs and 1498/10,005 patients (15.0%) discontinued therapy [warfarin = 236/1642 (14.4%) vs DOACs = 1262/8363 (15.1%)]. At 6 and 12 months respectively, among 7049 patients with a new diagnosis of AF within 6 months, adjusted discontinuation rates for warfarin versus DOACs were as follows: [6 months: 7.9%, 95%CI (6.8%-9.0%) vs 9.6% (8.4%-10.7%), P = .16]; [12 months: 12.7% (11.0%-14.3%) vs 15.3% (13.6%-16.9%), P = .02)]. Patients who discontinued therapy with warfarin or DOACs had higher risk of adverse clinical outcomes including: all-cause mortality and cardiovascular death (CV) than those who continued treatment., Conclusion: In a community based AF cohort, adjusted rates of discontinuation at 12-months were higher in DOAC-treated versus VKA-treated patients. Discontinuation of oral anticoagulation was associated with increased absolute risk of all-cause mortality and CV death., Clinical Trial Registration: URL:https://clinicaltrials.gov. Unique Identifier: NCT01701817., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The ACC/AHA guidelines for primary prevention rely on the Pooled Cohort Risk Equations (PCE) risk estimates of atherosclerotic cardiovascular disease (ASCVD) to guide treatment decisions. In light of the PCE being derived in younger populations, their accuracy in older adults is uncertain., Objective: To evaluate the predictive accuracy and calibration of the PCE in older individuals., Design and Setting: We estimated CVD predicted and observed risk among individuals from four large prospective cohort studies: Cardiovascular Health Study, Multiethnic Study of Atherosclerosis, Framingham Original, and Framingham Offspring., Participants: 12,527 overall individuals without ASCVD, including 9864 individuals aged 40-74 years and 2663 aged ≥75 years., Measurements: We examined the operating characteristics of the PCE to estimate 5-year risk of stroke, MI, and CHD death overall and by age and sex strata. The associations between individual components of the PCE and cardiovascular events by age group (≥75 vs 40-74 years) were also evaluated., Results: The PCE had low discrimination for 5-year ASCVD risk in older (≥75 years) (c-statistic = 0.62, 95% CI 0.60-0.65) vs. younger (40-74 years) adults (c-statistic = 0.75, 95% CI 0.73-0.76). Calibration of the PCE was suboptimal in both older and younger adults, overestimating risk in the highest risk groups. Performance of the PCE in older adults was similarly poor when stratified by sex and age ≥ 80 years., Limitations: Since the PCE were derived from similar cohorts, though using different age groups and exams, this analysis likely overestimates the performance of the PCE., Conclusion: The performance of the PCE for ASCVD risk estimation in older adults is suboptimal; new models to effectively risk-stratify older adults are needed.

Background: There is limited evidence on the effectiveness and safety of direct-acting oral anticoagulants in patients with nonvalvular atrial fibrillation (NVAF) and advanced chronic kidney disease (CKD). This study compared the risks of ischemic stroke/systemic embolism (ISSE) and major bleeding in patients with NVAF and stage IV-V CKD treated with rivaroxaban or warfarin., Methods: Patients with NVAF and stage IV-V CKD who initiated rivaroxaban or warfarin treatment between November 2011 and June 2018 were selected from the Optum® Deidentified Electronic Health Record Database. Propensity score matching was used to balance rivaroxaban and warfarin patients on 112 measured baseline covariates. ISSE and major bleeding events over 2 years following treatment initiation were ascertained with validated end point definitions. Outcomes were analyzed as time-to-event data using Kaplan-Meier survival estimators and Cox regression., Results: A total of 781 eligible rivaroxaban-treated patients were propensity score-matched to 1,536 warfarin-treated patients; baseline covariates were well balanced after matching (absolute standardized differences <0.1). The average patient age was 80 years; 60.5% were female; 81.3% and 18.7% had CKD stage IV and V, respectively. Hazard ratios for rivaroxaban compared to warfarin were 0.93 (95% CI 0.46-1.90, P = .85) for the risk of ISSE and 0.91 (95% CI 0.65-1.28, P = .60) for major bleeding., Conclusions: No statistically significant difference in the risk of ISSE or major bleeding was found between rivaroxaban- and warfarin-treated patients. Although further study is needed, rivaroxaban appears to be a reasonable alternative to warfarin for ISSE prevention in the setting of NVAF and stage IV-V CKD., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Patients with atrial fibrillation on oral anticoagulation (OAC) undergoing cardiac catheterization face risks for embolic and bleeding events, yet information on strategies to mitigate these risks in contemporary practice is lacking., Methods: We aimed to describe the clinical/procedural characteristics of a contemporary cohort of patients with atrial fibrillation on OAC who underwent cardiac catheterization. Use of bleeding avoidance strategies and bridging therapy were described and outcomes including death, stroke, and major bleeding at 30 days and 1 year were compared by OAC type., Results: Of 13 404 patients in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II Registry from 2013 to 2016, 741 underwent cardiac catheterization (139 with percutaneous coronary intervention) in the setting of OAC. The patients' median age was 71, 61.8% were male, white (87.2%), had hypertension (83.7%), hyperlipidemia (72.1%), diabetes mellitus (31.6%), and chronic kidney disease (28.2%); 20.2% received warfarin while 79.8% received direct acting oral anticoagulant. One third of patients underwent radial artery access, and bivalirudin was used in 4.6%. Bridging therapy was used more often in patients on warfarin versus direct acting oral anticoagulant (16.7% versus10.0%). OAC was interrupted in 93.8% of patients. Patients on warfarin versus direct acting oral anticoagulant were equally likely to restart OAC (58.0% versus 60.7%), had similar use of antiplatelet therapy (44.0% versus 41.3%) after catheterization, and had similar rates of myocardial infarction and death at 1 year, but higher rates of major bleeding (43.3 versus 12.9 events/100 patient years) and stroke (4.9 versus 1.9 events/100 patient years)., Conclusions: In a real-world registry of patients with atrial fibrillation undergoing cardiac catheterization, most cases are elective, performed by femoral access, with interruption of OAC. Bleeding avoidance strategies such as radial artery access and bivalirudin were used infrequently and use of bridging therapy was uncommon. Nearly 40% of patients did not restart OAC postprocedure, exposing patients to risk for stroke. Further research is necessary to optimize the management of patients with atrial fibrillation undergoing cardiac catheterization.

Purpose: Patients with atrial fibrillation (AF) undergoing cardiac surgery are at substantially increased risk for stroke. Increasing evidence has suggested that surgical left atrial appendage occlusion (S-LAAO) may have the potential to substantially mitigate this stroke risk; however, S-LAAO is performed in a minority of patients with AF undergoing cardiac surgery. We sought to identify factors associated with usage of S-LAAO., Methods: In a nationally-representative, contemporary cohort (07/2011-06/2012) of older patients undergoing cardiac surgery with preoperative AF (n = 11,404) from the Medicare-linked Society of Thoracic Surgeons Adult Cardiac Surgery Database, we evaluated patient and hospital characteristics associated with S-LAAO use by employing logistic and linear regression models., Results: In this cohort (average age, 76 years; 39% female), 4177 (37%) underwent S-LAAO. Neither S-LAAO nor discharge anticoagulation was used in 25% ("unprotected" patients). The overall propensity for S-LAAO decreased significantly with increasing CHA 2 DS 2 -VASc (congestive heart failure; hypertension; age 75 years or older; diabetes mellitus; stroke, transient ischemic attack, or thromboembolism; vascular disease; age 65 to 74 years; sex category (female)) score (p trend  < 0.001). There was substantial variability in S-LAAO use across geographic regions, and S-LAAO was more commonly performed at academic and higher-volume valve surgery centers., Conclusions: Substantial variability in use of S-LAAO exists. In many instances, the procedure is being deferred in the patients that may be poised to benefit the most (i.e., those with increased CHA 2 DS 2 -VASc score-defined stroke risk).

Background: Atrial fibrillation (AF) is common in patients with end-stage renal disease (ESRD). The impact of oral anticoagulation (OAC) in ESRD patients is uncertain., Objectives: The purpose of this study was to describe patterns of OAC use in ESRD patients with AF and their associations with cardiovascular outcomes., Methods: Using Medicare fee-for-service 5% claims data from 2007 to 2013, we analyzed treatment and outcomes in a cohort of patients with ESRD and AF. Prescription drug benefit information was used to determine the timing of OAC therapy. Cox proportional hazards modeling was used to compare outcomes including death, all-cause stroke, ischemic stroke, hemorrhagic stroke, and bleeding hospitalizations in ESRD patients treated with or without OAC., Results: The cohort included 8,410 patients with AF and ESRD. A total of 3,043 (36.2%) patients were treated with OAC at some time during the study period. Propensity scores used to match 1,519 patients with AF and ESRD on OAC with 3,018 ESRD patients without OAC. Treatment with OAC was not associated with hospitalization for stroke (hazard ratio [HR]: 1.00; 95% confidence interval [CI]: 0.23 to 1.35; p = 0.97) or death (HR: 1.02; 95% CI: 0.94 to 1.10; p = 0.62). OAC was associated with an increased risk of hospitalization for bleeding (HR: 1.26; 95% CI: 1.09 to 1.46; p = 0.0017) and intracranial hemorrhage (HR: 1.30; 95% CI: 1.07 to 1.59; p = 0.0094)., Conclusions: OAC utilization was low in patients with AF and ESRD. We found no association between OAC use and reduced risk of stroke or death. OAC use was associated with increased risks of hospitalization for bleeding or intracranial hemorrhage. Alternative stroke prevention strategies are needed in patients with ESRD and AF., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background Guidelines recommend against the use of intravenous tPA (tissue-type plasminogen activator; IV tPA) in acute ischemic stroke patients with prior ischemic stroke within 3 months. However, there are limited data on the safety of IV tPA in this population. Methods and Results A retrospective observational study of patients ≥66 years of age linked to Medicare claims and treated with IV tPA at Get With The Guidelines-Stroke hospitals (February 2009 to December 2015). We identified 293 patients treated with IV tPA who had a prior ischemic stroke within 3 months and 30 655 with no history of stroke. Patients with prior stroke had a higher stroke severity (median National Institutes of Health Stroke Scale, 11 [6-19] versus 11 [6-18]; absolute standardized difference, 11.2%) and a higher prevalence of cardiovascular comorbidities. Patients with prior stroke had a higher unadjusted risk for symptomatic intracranial hemorrhage (7.7% versus 4.8%) and in-hospital mortality (12.6% versus 8.9%), but these differences were not statistically significant after adjustment. When stratified by prespecified time epochs, the elevated risk for symptomatic intracranial hemorrhage was seen only within the first 14 days (16.3% versus 4.8%; adjusted odds ratio [aOR], 3.7 [95% CI, 1.62-8.43]) but not in other epochs (2.1% versus 4.8%; aOR, 0.38 [95% CI, 0.05-2.79] for 15-30 days and 7.4% versus 4.8%; aOR, 1.36 [95% CI, 0.77-2.40] for 31-90 days). In addition, patients with prior stroke were significantly more likely to have a combined outcome of in-hospital mortality or discharge to hospice (25.9% versus 17.0%; aOR, 1.70 [95% CI, 1.21-2.38]), less likely to be discharged to home (28.3% versus 32.3%; aOR, 0.72 [95% CI, 0.54-0.98]), or to have good functional outcomes at discharge (modified Rankin Scale, 0-1; 11.3% versus 20.0%; aOR, 0.46 [95% CI, 0.24-0.89]). Conclusions Stroke providers need to continue to be vigilant about the safety of IV tPA in patients with prior stroke, particularly those with an event in the previous 14 days.

For 4 decades, antithrombotic therapy with aspirin has been a cornerstone of secondary prevention for patients with chronic atherosclerotic cardiovascular disease (ASCVD). Unfortunately, despite the use of evidence-based therapies, patients with ASCVD continue to have recurrent major adverse cardiovascular events including death, myocardial infarction, and stroke-at a rate of approximately 2%-4% per year. To combat this continuing risk, several recent trials have evaluated the efficacy and safety of more intensive antithrombotic strategies through prolonged dual antiplatelet therapy (DAPT), combining a P2Y12 receptor antagonists and low-dose aspirin, or alternatively applying a dual pathway inhibition approach, combining low-dose non-vitamin K antagonist anticoagulant and low-dose aspirin. Both combination strategies have been shown to reduce recurrent ischemic events but at the cost of increased bleeding events. The clinical application of these antithrombotic strategies requires clinicians to assess and balance the risk of recurrent ischemic and bleeding events in an individual patient. Furthermore, clinicians may also need to adapt their antithrombotic strategies to achieve best patient outcomes, as ASCVD is a progressive disease and the risks of cardiovascular ischemic and bleeding events may shift over time. This state-of-the-art article reviews evidence from the trials and provides a practical approach to the application of DAPT and dual pathway antithrombotic therapy in the long-term management of patients with chronic ASCVD., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Studies evaluating the effects of atrial fibrillation (AF) catheter ablation versus antiarrhythmic therapy on outcomes have shown mixed results. In addition, guidelines recommend continuing oral anticoagulation (OAC) after ablation for those at risk of stroke, but real-world data are lacking., Methods: We evaluated outcomes including death, myocardial infarction, stroke or systemic embolism, intracranial bleeding, major bleeding, and hospitalization in patients undergoing AF ablation compared with a propensity score matched cohort of patients treated with anti-arrhythmic medications only in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation registries. Cox proportional hazards regression was performed to evaluate the association between AF ablation and outcomes. We then evaluated patterns of treatment with OAC among AF ablation patients., Results: Among 21 595 patients, 1190 (6%) underwent de novo AF ablation. Our propensity score-matched cohort included 1087 patients who underwent AF ablation matched 1:1 with 1087 patients treated with antiarrhythmic medications only. There were no significant differences in the risk of all-cause and cardiovascular death, and most other major adverse cardiovascular and neurological events. AF catheter ablation was associated with an increased risk of all-cause hospitalization during follow-up (hazard ratio, 1.24 [95% CI, 1.05-1.46]), particularly in the first 3 months (the standard blanking period) after the procedure. Among those who underwent AF ablation with a CHA 2 DS 2 VASc score ≥2 for men and ≥3 for women, 23% had OAC discontinued after ablation. Among those who discontinued OAC, the median time to discontinuation was 6.2 months., Conclusions: In this large US national registry, we found no difference in adjusted rates of cardiovascular or all-cause death between patients treated with AF catheter ablation and antiarrhythmic medications only. Notably, discontinuation of OAC after ablation remains relatively common despite guideline recommendations for continued stroke prevention therapy in patients at risk of stroke.

Background: We investigated the use of different antithrombotic therapies at baseline among patients with a history of atrial fibrillation (AF), type 2 diabetes, and established atherosclerotic cardiovascular disease (ASCVD) enrolled in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS)., Methods: TECOS participants with a history of AF were stratified by CHA 2 DS 2 -VASc score and their antithrombotic use evaluated. Cox proportional hazards models were employed to explore possible associations between history of AF and prespecified clinical outcomes after adjusting for key baseline characteristics., Results: Of the 14,671 TECOS participants, 1167 (8%) had a history of AF, of whom 51.6% were using vitamin K antagonists (VKA); 31.2% used VKA alone, 16.9% used aspirin plus VKA, 1.8% used clopidogrel plus VKA, and 1.7% used aspirin and clopidogrel plus VKA. Aspirin was used by 56.8%: 30.9% used aspirin alone and 7.3% aspirin plus clopidogrel. Clopidogrel alone was used by 2.9%, and 7.3% were not using any antithrombotic medication. Participants with a history of AF had a higher risk of cardiovascular events, including hospitalization for heart failure and all-cause mortality, than those without AF. White, older men with prior myocardial infarction, heart failure, peripheral artery disease, or prior stroke were more likely to develop new-onset AF than others without these characteristics., Conclusions: Almost half of high-risk AF patients with diabetes and established ASCVD in TECOS were not treated with anticoagulation therapy despite clear guideline recommendations for such therapy, highlighting the challenge and potential for clinical improvements in managing these patients in clinical practice., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00790205., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background Intravenous recombinant tissue-type plasminogen activator (rtPA) remains the only medical therapy to improve outcomes for acute ischemic stroke (AIS), but the safety of rtPA in AIS patients with a history of recent myocardial infarction (MI) remains controversial. Methods and Results We sought to determine whether the presence of recent MI would alter the risk of mortality and rtPA-related complications. Multivariate logistic regression models were used to compare in-hospital outcomes between rtPA-treated AIS patients with recent MI within 3 months and those with no history of MI from the Get With The Guidelines-Stroke hospitals between February 2009 and December 2015. Among 40 396 AIS patients aged ≥65 years treated with rtPA, 241 (0.6%) had recent MI, of which 19.5% were ST-segment-elevation myocardial infarction. Patients with recent MI had more severe stroke than those without (median National Institutes of Health Stroke Scale [interquartile range]: 13.0 [7.0-20.0] versus 11.0 [6.0-18.0]). Recent MI was associated with an increased risk of mortality compared with no history of MI (17.4% versus 9.0%; adjusted odds ratio 1.60 [95% CI, 1.10-2.33]; P=0.014), but no statistically significant differences in rtPA-related complications (13.5% versus 9.4%; adjusted odds ratio 1.28 [0.88-1.86]; P=0.19). Recent ST-segment-elevation myocardial infarction was associated with higher risk of death and rtPA-related complications, but non-ST-segment-elevation myocardial infarction was not. Conclusions Among older AIS patients treated with rtPA, recent MI was associated with an increased risk of in-hospital mortality. Further investigations are necessary to determine whether the benefit of rtPA outweighs its risk among AIS patients with recent MI.

Objective: To assess long-term healthcare costs related to ischemic stroke and systemic embolism (stroke/SE) and major bleeding (MB) events in patients with non-valvular atrial fibrillation (NVAF) treated with non-vitamin K antagonist oral anticoagulants (NOACs). Materials and methods: Optum's Clinformatics Data Mart database from 1/2009-12/2016 was analyzed. Adult patients with ≥1 stroke/SE hospitalization (index date) were matched 1:1 to patients without stroke/SE (random index date), based on propensity scores. Patients with an MB event were matched to patients without MB. All patients had an NOAC dispensing overlapping index date, ≥12 months of eligibility pre-index date, and ≥1 NVAF diagnosis. The observation period spanned from the index date until the earliest date of death, switch to warfarin, end of insurance coverage, or end of data availability. Mean costs were evaluated: (1) per-patient-per-year (PPPY) and (2) at 1, 2, 3, and 4 years using Lin's method. Results: The cost differences were, respectively, $48,807 and $28,298 PPPY for NOAC users with stroke/SE ( n =  1,340) and those with MB ( n =  3,774) events compared to controls. Cost differences of patients with vs without stroke/SE were $49,876, $51,627, $57,822, and $60,691 at 1, 2, 3, and 4 years post-index, respectively ( p  < 0.001). These cost differences were $31,292, $35,658, $44,069, and $47,022 for patients with vs without MB after 1, 2, 3, and 4 years post-index, respectively ( p  < 0.001). Limitations: Limitations include unobserved confounders, coding and/or billing inaccuracies, limited sample sizes over longer follow-up, and the under-reporting of mortality for deaths occurring after 2011. Conclusions: The incremental healthcare costs incurred by patients with vs without stroke/SE was nearly twice as high as those of patients with vs without MB. Moreover, each additional year up to 4 years after the first event was associated with an incremental cost for patients with a stroke/SE or MB event compared to those without an event.

Background: The necessity for rapid evaluation and treatment of acute ischemic stroke with intravenous tPA (tissue-type plasminogen activator) may increase the risk of administrating tPA to patients presenting with noncerebrovascular conditions that closely resemble stroke (stroke mimics). However, there are limited data on thrombolysis safety in stroke mimics., Methods and Results: Using data from the Get With The Guidelines-Stroke Registry, we identified 72 582 patients with suspected ischemic stroke treated with tPA from 485 US hospitals between January 2010 and December 2017. We documented the use of tPA in stroke mimics, defined as patients who present with stroke-like symptoms, but after workup are determined not to have suffered from a stroke or transient ischemic attack, and compared characteristics and outcomes in stroke mimics versus those with ischemic stroke. Overall, 3.5% of tPA treatments were given to stroke mimics. Among them, 38.2% had a final nonstroke diagnoses of migraine, functional disorder, seizure, and electrolyte or metabolic imbalance. Compared with tPA-treated true ischemic strokes, tPA-treated mimics were younger (median 54 versus 71 years), had a less severe National Institute of Health Stroke Scale (median 6 versus 8), and a lower prevalence of cardiovascular risk factors, except for a higher prevalence of prior stroke/transient ischemic attack (31.3% versus 26.1%, all P<0.001). The rate of symptomatic intracranial hemorrhage was lower in stroke mimics (0.4%) as compared with 3.5% in ischemic strokes (adjusted odds ratio, 0.29; 95% CI, 0.17-0.50). In-hospital mortality rate was significantly lower in stroke mimics (0.8% versus 6.2%, adjusted odds ratio, 0.31; 95% CI, 0.20-0.49). Patients with stroke mimics were more likely to be discharged to home (83.8% versus 49.3%, adjusted odds ratio, 2.97; 95% CI, 2.59-3.42) and to ambulate independently at discharge (78.6% versus 50.6%, adjusted odds ratio, 1.86; 95% CI, 1.61-2.14)., Conclusions: In this large cohort of patients treated with tPA, relatively few patients who received tPA for presumed stroke were ultimately not diagnosed with a stroke or transient ischemic attack. The complication rates associated with tPA in stroke mimics were low. Despite the potential risk of administering tPA to stroke mimics, opportunity remains for continued improvement in the rapid and accurate diagnosis and treatment of ischemic stroke.

Importance: Randomized clinical trials suggest benefit of endovascular-reperfusion therapy for large vessel occlusion in acute ischemic stroke (AIS) is time dependent, but the extent to which it influences outcome and generalizability to routine clinical practice remains uncertain., Objective: To characterize the association of speed of treatment with outcome among patients with AIS undergoing endovascular-reperfusion therapy., Design, Setting, and Participants: Retrospective cohort study using data prospectively collected from January 2015 to December 2016 in the Get With The Guidelines-Stroke nationwide US quality registry, with final follow-up through April 15, 2017. Participants were 6756 patients with anterior circulation large vessel occlusion AIS treated with endovascular-reperfusion therapy with onset-to-puncture time of 8 hours or less., Exposures: Onset (last-known well time) to arterial puncture, and hospital arrival to arterial puncture (door-to-puncture time)., Main Outcomes and Measures: Substantial reperfusion (modified Thrombolysis in Cerebral Infarction score 2b-3), ambulatory status, global disability (modified Rankin Scale [mRS]) and destination at discharge, symptomatic intracranial hemorrhage (sICH), and in-hospital mortality/hospice discharge., Results: Among 6756 patients, the mean (SD) age was 69.5 (14.8) years, 51.2% (3460/6756) were women, and median pretreatment score on the National Institutes of Health Stroke Scale was 17 (IQR, 12-22). Median onset-to-puncture time was 230 minutes (IQR, 170-305) and median door-to-puncture time was 87 minutes (IQR, 62-116), with substantial reperfusion in 85.9% (5433/6324) of patients. Adverse events were sICH in 6.7% (449/6693) of patients and in-hospital mortality/hospice discharge in 19.6% (1326/6756) of patients. At discharge, 36.9% (2132/5783) ambulated independently and 23.0% (1225/5334) had functional independence (mRS 0-2). In onset-to-puncture adjusted analysis, time-outcome relationships were nonlinear with steeper slopes between 30 to 270 minutes than 271 to 480 minutes. In the 30- to 270-minute time frame, faster onset to puncture in 15-minute increments was associated with higher likelihood of achieving independent ambulation at discharge (absolute increase, 1.14% [95% CI, 0.75%-1.53%]), lower in-hospital mortality/hospice discharge (absolute decrease, -0.77% [95% CI, -1.07% to -0.47%]), and lower risk of sICH (absolute decrease, -0.22% [95% CI, -0.40% to -0.03%]). Faster door-to-puncture times were similarly associated with improved outcomes, including in the 30- to 120-minute window, higher likelihood of achieving discharge to home (absolute increase, 2.13% [95% CI, 0.81%-3.44%]) and lower in-hospital mortality/hospice discharge (absolute decrease, -1.48% [95% CI, -2.60% to -0.36%]) for each 15-minute increment., Conclusions and Relevance: Among patients with AIS due to large vessel occlusion treated in routine clinical practice, shorter time to endovascular-reperfusion therapy was significantly associated with better outcomes. These findings support efforts to reduce time to hospital and endovascular treatment in patients with stroke.

Background: Treatment patterns and outcomes of individuals with vascular disease who have new-onset atrial fibrillation (AF) are not well characterized., Methods: Among patients with new-onset AF, we analyzed treatment and outcomes in those with or without vascular disease in the ORBIT-AF II registry. Vascular disease was defined as coronary disease with or without myocardial infarction (MI) or revascularization, or peripheral artery disease. The primary outcomes included major adverse cardiovascular or neurological events (MACNE) and major bleeding. Cox proportional hazard models were used to adjust the difference in patient characteristics., Results: Overall 1920 of 6203 (31.0%) of new-onset AF had vascular disease. In patients with vascular disease, 62.2% of those were treated with direct oral anticoagulants (DOACs) and 23.4% with warfarin. Dual therapy and triple therapy were used in 36.9% and 4.9%, respectively. Vascular disease patients had increased risk of MACNE (adjusted hazard ratio [aHR] 1.83 [95%CIs 1.32-2.55]), but not major bleeding (aHR 1.24 [0.95-1.63]). Among patients with vascular disease, relative to those on warfarin, those treated with DOACs had similar risk for MACNE (aHR 1.20 [0.77-1.87]) but lower risks for bleeding, although it did not reach statistical significance (aHR 0.70 [0.43-1.15]). Concomitant antiplatelet therapy was associated with higher bleeding (aHR 2.27 [1.38-3.73]) with no apparent reduction in MACNE (aHR 1.50 [1.00-2.25])., Conclusions: Most patients with AF and vascular disease were managed with oral anticoagulation. About half of them were also treated with concomitant antiplatelet therapy, which was associated with increased risk of bleeding, without evidence of improved cardiovascular outcomes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To determine whether young adults (≤40 years old) with acute ischemic stroke are less likely to receive IV tissue plasminogen activator (tPA) and more likely to have longer times to brain imaging and treatment., Methods: We analyzed data from the Get With The Guidelines-Stroke registry for patients with acute ischemic stroke hospitalized between January 2009 and September 2015. We used multivariable models with generalized estimating equations to evaluate tPA treatment and outcomes between younger (age 18-40 years) and older (age >40 years) patients with acute ischemic stroke., Results: Of 1,320,965 patients with acute ischemic stroke admitted to 1,983 hospitals, 2.3% (30,448) were 18 to 40 years of age. Among these patients, 12.5% received tPA vs 8.8% of those >40 years of age (adjusted odds ratio [aOR] 1.63, 95% confidence interval [CI] 1.56-1.71). However, younger patients were less likely to receive brain imaging within 25 minutes (62.5% vs 71.5%, aOR 0.78, 95% CI 0.73-0.84) and to be treated with tPA within 60 minutes of hospital arrival (37.0% vs 42.8%, aOR 0.74, 95% CI 0.68-0.79). Compared to older patients, younger patients treated with tPA had a lower symptomatic intracranial hemorrhage rate (1.7% vs 4.5%, aOR 0.55, 95% CI 0.42-0.72) and lower in-hospital mortality (2.0% vs 4.3%, aOR 0.65, 95% CI 0.52-0.81)., Conclusions: In contrast to our hypothesis, younger patients with acute ischemic stroke were more likely to be treated with tPA than older patients, but they were more likely to experience delay in evaluation and treatment. Compared with older patients, younger patients had better outcomes, including fewer intracranial hemorrhages., (© 2019 American Academy of Neurology.)

Background: There are limited data regarding clinical outcomes and healthcare resource utilization of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) who are morbidly obese (body mass index >40 kg/m 2 or body weight >120 kg)., Methods: Using data from 2 US healthcare claims databases, we identified patients initiating rivaroxaban or warfarin who had ≥1 medical claim with an AF diagnosis, a diagnostic code for morbid obesity (ICD-9: 278.01, V85.4%; ICD-10: E66.01%, E66.2%, Z68.4%), and a minimum continuous enrollment of 12 months before and 3 months after treatment initiation. Patients were excluded if they had mitral stenosis, a mechanical heart valve procedure, an organ/tissue transplant, or an oral anticoagulant prescription prior to the index date. Rivaroxaban and warfarin patients were 1:1 propensity score matched. Conditional logistic regression was used to compare ischemic stroke/systemic embolism and major bleeding risk. Generalized linear models were used to compare healthcare resource utilization and costs., Results: A total of 3563 matched pairs of morbidly obese AF patients treated with rivaroxaban or warfarin were identified. The majority (81.4%) of patients in the rivaroxaban cohort were receiving the 20 mg dose. The rivaroxaban and warfarin cohorts were well balanced after propensity score matching. The risks of ischemic stroke/systemic embolism and major bleeding were similar for rivaroxaban and warfarin users (stroke/systemic embolism: 1.5% vs 1.7%; odds ratio [OR]: 0.88; 95% confidence interval [CI]: 0.60, 1.28; P = .5028; major bleeding: 2.2% vs 2.7%; OR: 0.80; 95% CI: 0.59, 1.08; P = .1447). Total healthcare costs including medication costs per patient per year (PPPY) were significantly lower with rivaroxaban versus warfarin ($48,552 vs $52,418; P = .0025), which was primarily driven by lower hospitalization rate (50.2% vs 54.1%; P = .0008), shorter length of stay (7.5 vs 9.1 days; P = .0010), and less outpatient service utilization (86 vs 115 visits PPPY; P < .0001)., Conclusions: Morbidly obese AF patients treated with rivaroxaban had comparable risk of ischemic stroke/systemic embolism and major bleeding as those treated with warfarin, but lower healthcare resource utilization and costs., (Copyright © 2019 Janssen Scientific Affairs, LLC. Published by Elsevier Inc. All rights reserved.)

Background and Purpose- Acute ischemic stroke patients with history of prior ischemic stroke plus concomitant diabetes mellitus (DM) were excluded from the ECASS III trial (European Cooperative Acute Stroke Study) because of safety concerns. However, there are few data on use of intravenous tissue-type plasminogen activator and symptomatic intracerebral hemorrhage or outcomes in this population. Methods- Using data from the Get With The Guidelines-Stroke Registry between February 2009 and September 2017 (n=1619 hospitals), we examined characteristics and outcomes among patients with acute ischemic stroke treated with tissue-type plasminogen activator within the 3- to 4.5-hour window who had a history of stroke plus diabetes mellitus (HxS+DM) (n=2129) versus those without either history (n=16 690). Results- Compared with patients without either history, those with both prior stroke and DM treated with tissue-type plasminogen activator after an acute ischemic stroke had a higher prevalence of cardiovascular risk factors in addition to history of stroke, DM, and more severe stroke (National Institutes of Health Stroke Scale: median, 8 [interquartile range, 5-15] versus 7 [4-13]). The unadjusted rates of symptomatic intracerebral hemorrhage and in-hospital mortality were 4.3% (HxS+DM) versus 3.8% (without either history; P=0.31) and 6.2% versus 5.5% ( P=0.20), respectively. These differences were not statistically significant after risk adjustment (symptomatic intracerebral hemorrhage: adjusted odds ratio, 0.79 [95% CI, 0.51-1.21]; P=0.28; in-hospital mortality: odds ratio, 0.77 [95% CI, 0.52-1.14]; P=0.19). Unadjusted rate of functional independence (modified Rankin Scale score, 0-2) at discharge was lower in those with HxS+DM (30.9% HxS+DM versus 44.8% without either history; P≤0.0001), and this difference persisted after adjusting for baseline clinical factors (adjusted odds ratio, 0.76 [95% CI, 0.59-0.99]; P=0.04). Conclusions- Among patients with acute ischemic stroke treated with intravenous tissue-type plasminogen activator within the 3- to 4.5-hour window, HxS+DM was not associated with statistically significant increased symptomatic intracerebral hemorrhage or mortality risk.

Background Patient satisfaction with therapy is an important metric of care quality and has been associated with greater medication persistence. We evaluated the association of patient satisfaction with warfarin therapy to other metrics of anticoagulation care quality and clinical outcomes among patients with atrial fibrillation ( AF ). Methods and Results Using data from the ORBIT - AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registry, patients were identified with AF who were taking warfarin and had completed an Anti-Clot Treatment Scale ( ACTS ) questionnaire, a validated metric of patient-reported burden and benefit of oral anticoagulation. Multivariate regressions were used to determine association of ACTS burden and benefit scores with time in therapeutic international normalized ratio range ( TTR ; both ≥75% and ≥60%), warfarin discontinuation, and clinical outcomes (death, stroke, major bleed, and all-cause hospitalization). Among 1514 patients with AF on warfarin therapy (75±10 years; 42% women; CHA 2 DS 2 - VAS c 3.9±1.7), those most burdened with warfarin therapy were younger and more likely to be women, have paroxysmal AF , and to be treated with antiarrhythmic drugs. After adjustment for covariates, ACTS burden scores were independent of TTR ( TTR ≥75%: odds ratio, 1.01 [95% CI , 0.99-1.03]; TTR ≥60%: odds ratio, 1.01 [95% CI , 0.98-1.05]), warfarin discontinuation (odds ratio, 0.99; 95% CI , 0.97-1.01), or clinical outcomes. ACTS benefit scores were also not associated with TTR , warfarin discontinuation, or clinical outcomes. Conclusions In a large registry of patients with AF taking warfarin, ACTS scores provided independent information beyond other traditional metrics of oral anticoagulation care quality and identified patient groups at high risk for dissatisfaction with warfarin therapy.

Background: Stroke is a serious complication after transcatheter aortic valve replacement (TAVR), yet predictive models are not available. A new risk model for in-hospital stroke after TAVR was developed and used to estimate site-specific performance., Methods: We included 97,600 TAVR procedures from 521 sites in The Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry from July 2014 to June 2017. Association between baseline covariates and in-hospital stroke was estimated by logistic regression. Discrimination was evaluated by C-statistic. Calibration was tested internally via cross-validation. Hierarchical modeling was used to estimate risk-adjusted site-specific performance., Results: Median age was 82 years, 44,926 (46.0%) were women, and 1,839 (1.9%) had in-hospital stroke. Covariates associated with stroke (odds ratio) included transapical access (1.44), access excluding transapical and transfemoral (1.77), prior stroke (1.57), prior transient ischemic attack (1.50), preprocedural shock, inotropes or mechanical assist device (1.48), smoking (1.28), porcelain aorta (1.23), peripheral arterial disease (1.21), age per 5 years (1.11), glomerular filtration rate per 5 mL/min (0.97), body surface area per m 2 (0.55 male; 0.43 female), and prior aortic valve (0.78) and nonaortic valvular (0.42) procedures. The C-statistic was 0.622. Calibration curves demonstrated agreement between observed and expected stroke rates. Hierarchical modeling showed 10 (1.9%) centers with significantly higher odds ratios for in-hospital stroke than their peers., Conclusions: A risk model for in-hospital stroke after TAVR was developed from The Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry and used to estimate site-specific stroke performance. This model can serve as a valuable resource for quality improvement, clinical decision making, and patient counseling., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: To estimate the real-world (RW) impact of adherence to once-daily (QD: rivaroxaban and edoxaban) and twice-daily (BID: apixaban and dabigatran) non-vitamin K antagonist (NOACs) on the risk of stroke and major bleeding (MB) among non-valvular atrial fibrillation (NVAF) patients., Methods: First, claims from the Optum Clinformatics Data Mart database (July 2012-December 2016) were analyzed. Adult NVAF patients with ≥2 NOAC dispensings (index date) were included. The relationship between NOAC adherence (proportion of days covered ≥80%) and stroke/MB 1-year post-index was evaluated using adjusted Cox proportional hazards models. Second, the natural logarithm of hazard ratios (HRs) was multiplied to a literature-derived mean adherence difference between QD and BID NOACs yielding stroke and MB rates. Third, these rates were multiplied by 1-year Kaplan-Meier rates of stroke and MB which yielded the number of strokes prevented and MBs caused. Annual cost savings were evaluated using literature-based stroke ($81,414/patient) and MB ($63,905/patient) cost estimates., Results: In total, 54,280 patients were included. HRs for adherent vs non-adherent patients were 0.67 (p < .001) for stroke and 1.09 (p = .179) for MB. The claims-derived 1-year Kaplan-Meier rates were 3.0% and 3.4% for strokes and MBs, respectively. For 100,000 AF patients, 64 strokes were prevented (p < .001), and a non-significant number of MBs (n = 15, p < .191) were caused by QD vs BID NOACs annually, which leads to cost savings estimated at $58 million for QD NOACs., Conclusion: QD NOACs prevented a significant number of strokes and caused no significant increase in MBs compared to BID NOACs, which leads to significant net cost savings for NVAF patients in the US.

Background: Real-world data on the clinical outcomes of heart failure (HF) across the spectrum of ejection fraction (EF) and the prognostic value of B-type natriuretic peptide (BNP) have not been well examined., Hypothesis: The real-world association between the clinical outcomes of HF and EF or BNP levels may differ across different EF or BNP values., Methods: The Optum Integrated Claims-Clinical data (07/2009-09/2016) was used to identify adult patients with ≥1 HF diagnosis during hospitalization or emergency room visit. Three EF cohorts were formed: reduced (rEF; EF < 40%), mid-range (mrEF; EF 40%-49%), and preserved EF (pEF; EF ≥ 50%). Stratifications by BNP levels were performed using median BNP as cutoff between high vs low BNP (H-BNP vs L-BNP)., Results: In total, 7005 HF patients with EF measurements (2456 patients with both HF and BNP measurements) were identified. rEF patients had higher risk of stroke (hazard ratio [HR] = 1.57, P = 0.010) and acute myocardial infarction (AMI) (HR = 2.42, P < 0.001) compared to pEF patients. H-BNP was associated with a significantly higher risk of mortality (P < 0.001). rEF patients with H-BNP had a significantly higher risk of stroke than those with L-BNP., Conclusions: Patients with rEF had a significantly higher rate of stroke and AMI vs pEF patients, as did patients with H-BNP vs L-BNP. The present study is the first to show the real-world association of EF and BNP (alone and in combination) with clinical outcomes, further supporting the recommendation to use these markers in clinical practice. These results may help to guide future recommendations and improve the clinical management of HF., (© 2018 The Authors. Clinical Cardiology Published by Wiley Periodicals, Inc.)

Background: Translating evidence into clinical practice in the management of acute ischemic stroke (AIS) and transient ischemic attack (TIA) is challenging especially in low- and middle-income countries., Objectives: The aim of this study is to assess the effect of a multifaceted quality improvement intervention on adherence to evidence-based therapies for AIS and TIA patients care., Design: We designed a pragmatic, 2-arm cluster-randomized trial involving 36 clusters and 1624 patients from Brazil, Argentina, and Peru. Hospitals are randomized to receive a multifaceted quality improvement intervention (intervention group) or to routine care (control group). The BRIDGE Stroke multifaceted quality improvement intervention includes case management, reminders, health care providers' educational materials (including treatment algorithms), interactive workshops, and audit and feedback reports. Primary outcome is a composite adherence score to AIS and TIA performance measures. Secondary outcomes include an "all or none" composite end point to performance measures, the individual components of the composite end points, and clinical outcomes at 90 days following admission (stroke recurrence, death, and disability measured by the modified Rankin scale)., Summary: The BRIDGE Stroke Trial is an international pragmatic evaluation of a multifaceted quality improvement intervention. If effective, this intervention could be potentially extended widely to improve the quality of care and outcomes of patients with AIS or TIA., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Stroke is the leading cause of death in China. Despite the wide dissemination of evidence-based guidelines, data about adherence to these in routine clinical practice are scarce. We conducted a study using a nationwide registry to evaluate the implementation of evidence-based stroke performance indicators and associated guidelines, for patients with an ischemic stroke in China., Methods and Results: The China National Stroke Registry is a prospective cohort study, including 12 416 patients diagnosed with acute ischemic stroke from 132 hospitals across China, for 1 year beginning September 2007. Twelve performance indicators were selected to evaluate the quality of stroke care. Multivariable Cox models were used to determine the association between optimal compliance and clinical outcomes. Conformity with performance measures ranged from a median of 6.5% for the use of intravenous tPA (tissue-type plasminogen activator) to 81.8% for early use of antithrombotics. The optimal compliance with all in-hospital measures was associated with 1-year death after admission (hazard ratio, 0.66; 95% CI, 0.55-0.79). The optimal compliance with all discharge measures was associated with the 1-year death after discharge (hazard ratio, 0.55; 95% CI, 0.44-0.69), 1-year stroke recurrence (hazard ratio, 0.81; 95% CI, 0.70-0.93), and favorable functional outcomes (defined as modified Rankin Scale score of ≤2) (hazard ratio, 1.10; 95% CI, 1.04-1.16)., Conclusions: Adherence to evidence-based ischemic stroke care measures in China revealed substantial gaps, and select measures were associated with improved outcomes. These findings support the need for ongoing quality measurement and improvement in stroke care in China.

Importance: Black and Hispanic patients are less likely than white patients to use oral anticoagulants for atrial fibrillation. Little is known about racial/ethnic differences in use of direct-acting oral anticoagulants (DOACs) for atrial fibrillation., Objective: To assess racial/ethnic differences in the use of oral anticoagulants, particularly DOACs, in patients with atrial fibrillation., Design, Setting, and Participants: This cohort study used data from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II, a prospective, US-based registry of outpatients with nontransient atrial fibrillation 21 years and older who were followed up from February 2013 to July 2016. Data were analyzed from February 2017 to February 2018., Exposures: Self-reported race/ethnicity as white, black, or Hispanic., Main Outcomes and Measures: The primary outcome was use of any oral anticoagulant, particularly DOACs. Secondary outcomes included the quality of anticoagulation received and oral anticoagulant discontinuation at 1 year., Results: Of 12 417 patients, 11 100 were white individuals (88.6%), 646 were black individuals (5.2%), and 671 were Hispanic individuals (5.4%) with atrial fibrillation. After adjusting for clinical features, black individuals were less likely to receive any oral anticoagulant than white individuals (adjusted odds ratio [aOR], 0.75 [95% CI, 0.56, 0.99]) and less likely to receive DOACs if an anticoagulant was prescribed (aOR, 0.63 [95% CI, 0.49-0.83]). After further controlling for socioeconomic factors, oral anticoagulant use was no longer significantly different in black individuals (aOR, 0.78 [95% CI, 0.59-1.04]); among patients using oral anticoagulants, DOAC use remained significantly lower in black individuals (aOR, 0.73 [95% CI, 0.55-0.95]). There was no significant difference between white and Hispanic groups in use of oral anticoagulants. Among patients receiving warfarin, the median time in therapeutic range was lower in black individuals (57.1% [IQR, 39.9%-72.5%]) and Hispanic individuals (51.7% [interquartile range {IQR}, 39.1%-66.7%]) than white individuals (67.1% [IQR, 51.8%-80.6%]; P < .001). Black and Hispanic individuals treated with DOACs were more likely to receive inappropriate dosing than white individuals (black patients, 61 of 394 [15.5%]; Hispanic patients, 74 of 409 [18.1%]; white patients, 1003 of 7988 [12.6%]; P = .01). One-year persistence on oral anticoagulants was the same across groups., Conclusions and Relevance: After controlling for clinical and socioeconomic factors, black individuals were less likely than white individuals to receive DOACs for atrial fibrillation, with no difference between white and Hispanic groups. When atrial fibrillation was treated, the quality of anticoagulant use was lower in black and Hispanic individuals. Identifying modifiable causes of these disparities could improve the quality of care in atrial fibrillation.

Background Adherence to evidence-based guidelines is an important quality indicator; yet, there is lack of assessment of adherence to performance measures in acute ischemic stroke for most world regions. Methods and Results We analyzed 19 604 patients with acute ischemic stroke in the China National Stroke Registry and 194 876 patients in the Get With The Guidelines--Stroke registry in the United States from June 2012 to January 2013. Compared with their US counterparts, Chinese patients were younger, had a lower prevalence of comorbidities, and had similar median, lower mean, and less variability in National Institutes of Health Stroke Scale (median 4 [25th percentile-75th percentile, 2-7], mean 5.4±5.6 versus median 4 [1-10], mean 6.8±7.7). Chinese patients were more likely to experience delays from last known well to hospital arrival (median 1318 [330-3209] versus 644 [142-2055] minutes), less likely to receive thrombolytic therapy (2.5% versus 8.1%), and more likely to experience treatment delays (door-to-needle time median 95 [72-112] versus 62 [49-85] minutes). Adherence to early and discharge antithrombotics, smoking cessation counseling, and dysphagia screening were relatively high (eg >80%) in both countries. Large gaps existed between China and the United States with regard to the administration of thrombolytics within 3 hours (18.3% versus 83.6%), door-to-needle time ≤60 minutes (14.6% versus 48.0%), deep venous thrombosis prophylaxis (65.0% versus 97.8%), anticoagulation for atrial fibrillation (21.0% versus 94.4%), lipid treatment (66.3% versus 95.8%), and rehabilitation assessment (58.8% versus 97.4%). Conclusions We found significant differences in clinical characteristics and gaps in adherence for certain performance measures between China and the United States. Additional efforts are needed for continued improvements in acute stroke care and secondary prevention in both nations, especially China.

Background Chronic kidney disease ( CKD ) is a common comorbidity in patients with atrial fibrillation. The presence of CKD complicates drug selection for stroke prevention and rhythm control. Methods and Results Patients enrolled in ORBIT AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) with baseline renal function and follow-up data were included (N=9019). CKD was defined as an estimated creatinine clearance <60 mL /min. Patient characteristics were compared by CKD status, and Cox proportional hazards modeling was used to examine the association between oral anticoagulant ( OAC ) use and outcomes and antiarrhythmic drug use and outcomes stratified by CKD stages. At enrollment, 3490 (39%) patients had an estimated creatinine clearance <60 mL /min. Patients with CKD were older and had higher CHA 2 DS 2 VAS c and Anticoagulant and Risk Factors in Atrial Fibrillation (ATRIA) scores. A rhythm control strategy was selected less frequently in patients with CKD , while OAC use was lower among Stage IV and V CKD patients. After adjustment, no significant interaction was noted for OAC and CKD on all-cause mortality ( P=0.5442) or cardiovascular death ( P=0.1233), although a trend for increased major bleeding ( P=0.0608) and stroke, systemic embolism or transient ischemic attack ( P=0.0671) was observed. No interaction was noted for antiarrhythmic drug use and CKD status on all-cause mortality ( P=0.9706), or stroke, systemic embolism or transient ischemic attack ( P=0.4218). Conclusions Patients with atrial fibrillation and CKD are less likely to be treated with rhythm control. Patients with advanced CKD are less likely to receive OAC . Finally, outcomes with OAC in patients with advanced CKD may be materially different with higher rates of both bleeding and stroke.

Background: The tradeoff in safety versus efficacy in substituting a non-vitamin K antagonist oral anticoagulant for a vitamin K antagonist (VKA) in the stented atrial fibrillation patient has not been quantitatively evaluated., Methods: Based on summary data from the PIONEER AF-PCI and RE-DUAL PCI trials, 4 antithrombotic regimens were compared with VKA-based triple therapy: (1) rivaroxaban (riva) 15 mg daily + P2Y 12 inhibitor, (2) riva 2.5 mg twice daily + P2Y 12 inhibitor + aspirin, (3) dabigatran (dabi) 110 mg twice daily + P2Y 12 inhibitor, and (4) dabi 150 mg twice daily + P2Y 12 inhibitor. A bivariate model with a noninferiority margin of 1.38 was used to simultaneously assess safety and efficacy. The safety end point was major or clinically relevant nonmajor bleeding by International Society on Thrombosis and Haemostasis definitions. The efficacy end point was a thromboembolic event (myocardial infarction, stroke, or systemic embolism), death, or urgent revascularization. The bivariate outcome, a measure of risk difference in the net clinical outcome, was compared between antithrombotic regimens., Results: All 4 non-vitamin K antagonist oral anticoagulant regimens were superior in bleeding and noninferior in efficacy compared with triple therapy with VKA. Riva 15 mg daily and 2.5 mg twice daily were associated with bivariate combined risk reductions of 5.6% (2.3%-8.8%) and 5.5% (2.1%-8.7%), respectively, and dabi 110 mg twice daily and 150 mg twice daily reduced the bivariate risk by 3.8% (0.5%-7.0%) and 6.3% (2.4%-9.8%), respectively., Conclusions: A bivariate analysis that simultaneously characterizes both risk and benefit demonstrates that riva- and dabi-based regimens were both favorable over VKA plus dual antiplatelet therapy among patients with atrial fibrillation undergoing PCI., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background and Purpose- Although there are no trials or large cohorts to inform clinical care, current guidelines caution against giving intravenous tPA (tissue-type plasminogen activator) to patients with acute ischemic stroke who are taking non-vitamin K antagonist oral anticoagulants (NOACs). We performed a literature review of intravenous tPA in patients treated with NOACs preceding stroke. Methods- A literature search of PubMed was performed encompassing January 2010 to March 2018. Patient characteristics, timing of last medication intake, laboratory testing, use of reversal, and outcomes ≤3 months after discharge were summarized. Results- We identified 55 studies with 492 NOAC patients receiving tPA (dabigatran, 181; rivaroxaban, 215; apixaban, 40; and unspecified NOAC, 56). Among patients with complete data, the median time from the last NOAC intake to symptom onset was 8 hours (interquartile range, 2.5-14.5), with 55.2% (80/145) within 12 hours. Few patients underwent sensitive laboratory tests, such as thrombin time, diluted thrombin time, or anti-Xa assays before tPA administration. The overall observed rates of symptomatic intracranial hemorrhage, mortality, and favorable outcomes (National Institutes of Health Stroke Scale score, ≤1; modified Rankin Scale score, 0-2; or neurological improvement in the National Institutes of Health Stroke Scale score, ≥8 points) were 4.3% (20/462), 11.3% (48/423), and 43.7% (164/375), respectively. Among dabigatran-treated patients, reversal with idarucizumab was associated with fewer symptomatic intracranial hemorrhage (4.5% [2/44] versus 7.4% [8/108]; unadjusted odds ratio, 0.60; 95% CI, 0.12-2.92), death (4.5% [2/44] versus 12.0% [13/108]; unadjusted odds ratio, 0.35; 95% CI, 0.08-1.61), and more favorable outcomes (79.1% [34/43] versus 39.2% [29/74]; unadjusted odds ratio, 5.86; 95% CI, 2.45-14.00), although the differences were not statistically significant for symptomatic intracranial hemorrhage and death. Conclusions- These preliminary observations suggest that tPA may be reasonably well tolerated without prohibitive risks of bleeding complications in selected patients on NOACs. Reversal of anticoagulant effects by idarucizumab for dabigatran-treated patients before tPA is an emerging strategy that was associated with more favorable outcomes.

Background: Bleeding is commonly cited as a reason for stopping oral anticoagulants (OACs). Whether minor bleeding events (nuisance bleeding, NB) in patients with atrial fibrillation on OACs are associated with OAC discontinuation, major bleeding, and stroke/systemic embolism (SSE) is unknown., Methods: Within the ORBIT-AF prospective, outpatient registry (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation), we identified 6771 patients ≥18 years of age at 172 sites with atrial fibrillation and eligible follow-up visits. NB was ascertained from the medical record and was defined as minor bleeding that did not require medical attention (eg, bruising, hemorrhoidal bleeding). We used multivariable pooled logistic regression modeling to evaluate the associations between NB and major bleeding and SSE in the 180 days after documentation of NB. Our unit of analysis was the patient visit, occurring at ≈6-month intervals for a median of 1.5 years following enrollment. Changes in anticoagulation treatment satisfaction after NB were examined descriptively in a subset of patients., Results: The median age of the overall population was 75.0 (interquartile range, 67.0-81.0); 90.0% were white and 42.5% were female. Among 6771 patients (18 560 visits), n=1357 (20.0%) had documented NB, for an incidence rate of 14.8 events per 100 person-years. Over 96.4% of patients remained on OAC therapy after the NB event. Overall, 287 (4.3%) patients experienced major bleeding and 64 (0.96%) had a SSE event during follow-up. NB was not associated with a significant increased risk of major bleeding over 6 months in models adjusting for the ATRIA bleeding score (Anticoagulation and Risk Factors in Atrial Fibrillation) (odds ratio, 1.04; 95% confidence interval, 0.68-1.60; P=0.86). NB was also not associated with increased SSE risk over 6 months in models adjusting for the CHA 2 DS 2 -VASc risk score (odds ratio, 1.24; 95% confidence interval, 0.53-2.91; P=0.62)., Conclusions: NB is common among patients with atrial fibrillation on OACs. However, NB was not associated with a higher risk of major bleeding or SSE over the next 6 months, suggesting its occurrence should not lead to changes in anticoagulation treatment strategies in OAC-treated patients., Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01165710.

Background Current American College of Cardiology/American Heart Association guidelines suggest that for patients with atrial fibrillation who are at low risk for stroke (CHA 2 DS 2 VASc=1) (or women with CHA 2 DS 2 VASc=2) a variety of treatment strategies may be considered. However, in clinical practice, patterns of treatment in these "low-risk" patients are not well described. The objective of this analysis is to define thromboembolic event rates and to describe treatment patterns in patients with low-risk CHA 2 DS 2 VASc scores. Methods and Results We compared characteristics, treatment strategies, and outcomes among patients with a CHA 2 DS 2 VASc=0, CHA 2 DS 2 VASc=1, females with a CHA 2 DS 2 VASc=2, and CHA 2 DS 2 VASc ≥2 in ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) I & II. Compared with CHA 2 DS 2 VASc ≥2 patients (84.2%), those with a CHA 2 DS 2 VASc=0 (60.3%), 1 (69.9%), and females with a CHA 2 DS 2 VASc score=2 (72.4%) were significantly less often treated with oral anticoagulation ( P<0.0001). Stroke rates were low overall and ranged from 0 per 100 patient-years in those with CHA 2 DS 2 VASc=0, 0.8 (95% confidence interval [CI] [0.5-1.2]) in those with CHA 2 DS 2 VASc=1, 0.8 (95% CI [0.4-1.6]) in females with a CHA 2 DS 2 VASc score=2, and 1.7 (95% CI [1.6-1.9]) in CHA 2 DS 2 VASc ≥2. All-cause mortality (per 100 patient-years) was highest in females with a CHA 2 DS 2 VASc score=2 (1.4) (95% CI [0.8-2.3]), compared with patients with a CHA 2 DS 2 VASc=0 (0.2) (95% CI [0.1-1.0]), and CHA 2 DS 2 VASc=1 (1.0) (95% CI [0.7-1.4]), but lower than patients with a CHA 2 DS 2 VASc ≥2 (5.7) (95% CI [5.4-6.0]). Conclusion The majority of CHA 2 DS 2 VASc=0-1 patients are treated with oral anticoagulation. In addition, the absolute risks of death and stroke/transient ischemic attack were low among both male and females CHA 2 DS 2 VASc=0-1 as well as among females with a CHA 2 DS 2 VASc score=2. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT01701817.

Importance: In China and other parts of the world, hospital personnel adherence to evidence-based stroke care is limited., Objective: To determine whether a multifaceted quality improvement intervention can improve hospital personnel adherence to evidence-based performance measures in patients with acute ischemic stroke (AIS) in China., Design, Setting, and Participants: A multicenter, cluster-randomized clinical trial among 40 public hospitals in China that enrolled 4800 patients hospitalized with AIS from August 10, 2014, through June 20, 2015, with 12-month follow-up through July 30, 2016., Interventions: Twenty hospitals received a multifaceted quality improvement intervention (intervention group; 2400 patients), including a clinical pathway, care protocols, quality coordinator oversight, and performance measure monitoring and feedback. Twenty hospitals participated in the stroke registry with usual care (control group; 2400 patients)., Main Outcomes and Measures: The primary outcome was hospital personnel adherence to 9 AIS performance measures, with co-primary outcomes of a composite of percentage of performance measures adhered to, and as all-or-none. Secondary outcomes included in-hospital mortality and long-term outcomes (a new vascular event, disability [modified Rankin Scale score, 3-5], and all-cause mortality) at 3, 6, and 12 months., Results: Among 4800 patients with AIS enrolled from 40 hospitals and randomized (mean age, 65 years; women, 1757 [36.6%]), 3980 patients (82.9%) completed the 12-month follow-up of the trial. Patients in intervention group were more likely to receive performance measures than those in the control groups (composite measure, 88.2% vs 84.8%, respectively; absolute difference, 3.54% [95% CI, 0.68% to 6.40%], P = .02). The all-or-none measure did not significantly differ between the intervention and control groups (53.8% vs 47.8%, respectively; absolute difference, 6.69% [95% CI, -0.41% to 13.79%], P = .06). New clinical vascular events were significantly reduced in the intervention group compared with the control group at 3 months (3.9% vs 5.3%, respectively; difference, -2.03% [95% CI, -3.51% to -0.55%]; P = .007), 6 months (6.3% vs 7.8%, respectively; difference, -2.18% [95% CI, -4.0% to -0.35%]; P = .02) and 12 months (9.1% vs 11.8%, respectively; difference, -3.13% [95% CI, -5.28% to -0.97%]; P = .005)., Conclusions and Relevance: Among 40 hospitals in China, a multifaceted quality improvement intervention compared with usual care resulted in a statistically significant but small improvement in hospital personnel adherence to evidence-based performance measures in patients with acute ischemic stroke when assessed as a composite measure, but not as an all-or-none measure. Further research is needed to understand the generalizability of these findings., Trial Registration: ClinicalTrials.gov Identifier: NCT02212912.

Background: The Thrombolysis in Myocardial Infarction (TIMI) Risk Score for Secondary Prevention (TRS2°P), a 0-to-9-point system based on the presence/absence of 9 clinical factors, was developed to classify the risk of major adverse cardiovascular events (MACE) (a composite of cardiovascular death, recurrent myocardial infarction, or ischemic stroke) among patients with a recent myocardial infarction. Its performance has not been examined internationally outside of a clinical trial setting., Methods and Results: We evaluated the performance of TRS2°P for predicting MACE in 53 599 patients with recent myocardial infarction in 5 international cohorts from New Zealand, South Korea, Sweden, and the United States participating in the Chronic Kidney Disease Prognosis Consortium. Overall, there were 19 444 cases of MACE across 5 cohorts over a mean follow-up of 5 years, and the overall MACE rate ranged from 5.0 to 18.4 (per 100 person-years). The TRS2°P showed modest calibration (Brier score ranged from 0.144 to 0.173) and discrimination (C-statistics >0.61 in all studies except 1 from Korea with 0.55) across cohorts relative to its original Brier score of 0.098 and C-statistic of 0.67 in the derived data set. Although there was some heterogeneity across cohorts, the 9 predictors in the TRS2°P were generally associated with higher MACE risk, with strongest associations observed (meta-analyzed adjusted hazard ratio 1.6-1.7) for history of heart failure, age ≥75 years, and prior stroke, followed by peripheral artery disease, kidney dysfunction, diabetes mellitus, and hypertension (hazard ratio 1.3-1.4). Prior coronary bypass graft surgery and smoking did not reach statistical significance (hazard ratio ≈1.1)., Conclusions: TRS2°P, a simple scoring system with 9 routine clinical factors, was modestly predictive of secondary events when applied in patients with recent myocardial infarction from diverse clinical and geographic settings., (© 2018 The Authors and Merck Sharpe & Dohme Corp. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Stroke is a serious complication of both transcatheter aortic valve replacement (TAVR) and carotid artery disease (CD). The implications of CD in patients undergoing TAVR are unclear., Methods and Results: The Society of Thoracic Surgeons and American College of Cardiology Transcatheter Valve Therapies Registry, consisting of data from consecutive US TAVR cases during the years 2013 to 2015, was linked to Medicare claims data to ascertain 30-day and 1-year cumulative incidence rates of stroke and all-cause mortality. We compared 30-day and 1-year stroke and mortality outcomes between patients with no-CD and patients with moderate, severe, and occlusive CD and adjusted for baseline covariates using proportional hazards models. Among 29 143 patients undergoing TAVR across 390 US sites, 22% had CD. Patients with CD had higher rates of prior hypertension, diabetes mellitus, stroke, and myocardial infarction. Observed in-hospital stroke rates were 2.0% among no-CD, 2.5% among moderate CD, 3.0% among severe CD, and 2.6% among occlusive CD. There was no association between the presence of CD and 30-day stroke (adjusted hazard ratio, 1.16; 95% confidence interval, 0.94-1.43) or mortality (adjusted hazard ratio, 1.10; 95% confidence interval, 0.95-1.28). There was no association between CD and 1-year stroke (adjusted hazard ratio, 1.03; 95% confidence interval, 0.86-1.24) or mortality (adjusted hazard ratio, 1.02; 95% confidence interval, 0.93-1.12). Furthermore, there was no significant risk-adjusted association between severity of CD and 30-day or 1-year stroke or mortality., Conclusions: CD is common among TAVR patients, present in 1 of 5. CD was not associated with an increased risk of stroke or mortality at 30 day or 1 year. Post-TAVR stroke seems to be because of mechanisms other than CD., (© 2018 American Heart Association, Inc.)

Importance: Antithrombotic therapies are effective in both primary and secondary stroke prophylaxis in high-risk patients with atrial fibrillation (AF), but they are often underused in community practice., Objective: To examine prestroke and poststroke antithrombotic treatment patterns and long-term outcomes in patients with AF presenting with ischemic stroke., Design, Setting, and Participants: A retrospective cohort study of Danish patients with AF, with a prestroke CHA2DS2-VASc score of 1 or higher for men and 2 or higher for women, and presenting with ischemic stroke was conducted from January 1, 2004, to January 31, 2017. Data on hospital admission, prescription fillings, and vital status were assessed using several Danish nationwide registries., Exposures: Patients who survived 100 days after discharge were divided into 3 groups according to poststroke antithrombotic therapy: oral anticoagulation (OAC) therapy, antiplatelet therapy alone, or no antithrombotic therapy., Main Outcomes and Measures: Long-term outcomes (thromboembolic events and bleeding complications) were examined using multivariable Cox regression analyses across the 3 groups., Results: Among 30 626 patients with AF admitted with ischemic stroke, 11 139 patients (36.3%) received OAC therapy (44.3% female; median age, 79 years [interquartile range, 73-85 years]), 11 874 (38.8%) received antiplatelet therapy alone (55.0% female; median age, 82 years [interquartile range, 75-88 years]), and 7613 (24.9%) received no antithrombotic therapy before stroke (53.8% female; median age, 80 years [interquartile range, 71-86 years]). Following stroke, 31.3% of those receiving antiplatelet therapy alone and 43.7% of those receiving no antithrombotic therapy before stroke shifted to OAC therapy. Yet, 37.5% of patients with stroke did not receive OAC therapy following stroke. However, OAC treatment rates increased over time. During a maximum of 10 years of follow-up, 17.5%, 21.2%, and 21.5% experienced a new thromboembolic event and 72.7%, 86.4%, and 86.2% died among those treated with OAC therapy, antiplatelet therapy, or no antithrombotic therapy, respectively. Poststroke OAC therapy was associated with lower risk of recurrent thromboembolic events (adjusted hazard ratio, 0.81; 95% CI, 0.73-0.89) and no significant difference in bleeding complications (adjusted hazard ratio, 0.97; 95% CI, 0.86-1.10), compared with no poststroke antithrombotic therapy. In contrast, there were no significant differences for those treated with poststroke antiplatelet therapy and no antithrombotic therapy., Conclusions and Relevance: Patients with AF receiving poststroke OAC therapy had lower risk of recurrent thromboembolic events. Our findings suggest a substantial opportunity for improving primary and secondary stroke prophylaxis in high-risk patients with AF.

Background: Mineralocorticoid receptor antagonist (MRA) therapy may be beneficial to patients with atrial fibrillation (AF), but little is known about their use in patients with AF and subsequent outcomes., Methods and Results: In order to better understand MRA use and subsequent outcomes, we performed a retrospective cohort study of the contemporary ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registry. AF progression and cardiovascular outcomes were compared using propensity-matched Cox proportional hazards modeling according to MRA use at baseline and new MRA use at follow-up versus patients with no MRA use. Among 7012 patients with nonpermanent AF, 320 patients were taking MRA at enrollment, and 416 patients initiated MRA use during follow-up. The mean patient age was 72.5 years, 56.3% were men, and 70.4% had paroxysmal AF. Among all patients taking MRAs, 434 (59.0%) had heart failure, 655 (89.0%) had hypertension, and 380 (51.6%) had both. After adjustment, new MRA use was not associated with reduced AF progression (hazard ratio, 1.18; 95% confidence interval, 0.88-1.58; P =0.27) but showed a trend towards lower risk of stroke, transient ischemic attack, or systemic embolism (hazard ratio, 0.17; 95% confidence interval, 0.02-1.23; P =0.08). Results were similar for a comparison of new MRA users and baseline MRA users compared with nonusers., Conclusions: In community-based outpatients with AF, the majority of MRA use was for heart failure and hypertension. MRA use also trended towards lower adjusted stroke risk. Future studies should test the hypothesis that MRA use may decrease the risk of stroke in patients with AF., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Non-vitamin K antagonist oral anticoagulants (NOACs) are indicated for stroke prevention in atrial fibrillation (AF) but require lower doses in certain patients. We sought to describe the frequency, appropriateness (according to Food and Drug Administration labeling), and outcomes of patients prescribed reduced doses of NOACs in community practice., Methods and Results: We analyzed data from the ORBIT-AF II (The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II) registry, a prospective, national, observational registry of AF patients. Among 7925 AF patients receiving NOACs, we assessed patterns of use of reduced NOAC doses and associated cardiovascular and bleeding outcomes at median follow-up of 1 year. Overall, 6636 patients (84%) received a NOAC at standard dose, which was consistent with US Food and Drug Administration labeling in 6376 (96%). Reduced NOAC dose was prescribed to 1289 (16% overall), which was consistent with Food and Drug Administration labeling in only 555 patients (43%). Compared with those whose NOAC dose was appropriately reduced, patients receiving inappropriate dose reductions were younger (median age 79 versus 84, P <0.0001) and had lower ORBIT bleeding risk scores (26% ≥4 versus 45%, P <0.0001). Compared with those appropriately receiving standard dosing, patients receiving inappropriately reduced-dose NOACs had higher unadjusted rates of thromboembolic events (2.11 versus 1.35 events per 100 patient years, hazard ratio 1.56, 95% confidence interval 0.92-2.67) and death (6.77 versus 2.60, hazard ratio 2.61, 95% confidence interval 1.86-3.67). After adjustment, outcomes were not significantly different but tended to favor patients dosed appropriately., Conclusions: The majority of dose reductions of NOACs in AF are inconsistent with US Food and Drug Administration recommendations. There appear to be opportunities to improve current NOAC dosing in community practice., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01701817., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)