Automated interpretations of single-lead electrocardiograms predict incident atrial fibrillation: The VITAL-AF trial.

BACKGROUND: Single-lead electrocardiograms (1L ECGs) are increasingly used for atrial fibrillation (AF) detection. Automated 1L ECG interpretation may have prognostic value for future AF in cases in which screening does not result in a short-term AF diagnosis. OBJECTIVE: We sought to investigate the association between automated 1L ECG interpretation and incident AF. METHODS: VITAL-AF was a randomized controlled trial investigating the effectiveness of screening for AF by 1L ECGs. For this study, participants were divided into 4 groups based on automated classification of 1L ECGs. Patients with prevalent AF were excluded. Associations between groups and incident AF were assessed by Cox proportional hazards models adjusted for risk factors. The start of follow-up was defined as 60 days after the latest 1L ECG (as some individuals had numerous screening 1L ECGs). RESULTS: The study sample included never screened (n = 16,306), normal (n = 10,914), other (n = 2675), and possible AF (n = 561). Possible AF had the highest AF incidence (5.91 per 100 person-years; 95% confidence interval [CI], 4.24-8.23). Possible AF was associated with greater hazard of incident AF compared with normal (adjusted hazard ratio, 2.48; 95% CI, 1.66-3.71). Other was associated with greater hazard of incident AF compared with normal (1.41; 95% CI, 1.04-1.90). CONCLUSION: In patients undergoing AF screening with 1L ECGs without prevalent AF or AF within 60 days of screening, presumptive positive and indeterminate 1L ECG interpretations were associated with future AF. Abnormal 1L ECG recordings may identify individuals at higher risk for future AF.

Cardiovascular Risk Estimation Is Suboptimal in People With HIV.

BACKGROUND: Established cardiovascular disease (CVD) risk prediction functions may not accurately predict CVD risk in people with HIV. We assessed the performance of 3 CVD risk prediction functions in 2 HIV cohorts. METHODS AND RESULTS: CVD risk scores were calculated in the Mass General Brigham and Kaiser Permanente Northern California HIV cohorts, using the American College of Cardiology/American Heart Association atherosclerotic CVD function, the FHS (Framingham Heart Study) hard coronary heart disease function and the Framingham Heart Study hard CVD function. Outcomes were myocardial infarction or coronary death for FHS hard coronary heart disease function; and myocardial infarction, stroke, or coronary death for American College of Cardiology/American Heart Association and FHS hard CVD function. We calculated regression coefficients and assessed discrimination and calibration by sex; predicted to observed risk of outcome was also compared. In the combined cohort of 9412, 158 (1.7%) had a coronary heart disease event, and 309 (3.3%) had a CVD event. Among women, CVD risk was generally underestimated by all 3 risk functions. Among men, CVD risk was underestimated by the American College of Cardiology/American Heart Association and FHS hard CVD function, but overestimated by the FHS hard coronary heart disease function. Calibration was poor for women using the FHS hard CVD function and for men using all functions. Discrimination in all functions was good for women (c-statistics ranging from 0.78 to 0.90) and moderate for men (c-statistics ranging from 0.71 to 0.72). CONCLUSIONS: Established CVD risk prediction functions generally underestimate risk in people with HIV. Differences in model performance by sex underscore the need for both HIV-specific and sex-specific functions. Development of CVD risk prediction models tailored to HIV will enhance care for aging people with HIV.

Effect of clinic-based single-lead electrocardiogram rhythm assessment on oral anticoagulation prescriptions in patients with previously diagnosed atrial fibrillation.

Background: Despite benefits of oral anticoagulation (OAC), many individuals with diagnosed atrial fibrillation (AF) do not receive OAC. Objective: The purpose of this study was to assess whether cardiac rhythm assessment for AF impacted use of OAC in patients with previously diagnosed AF. Methods: VITAL-AF was a cluster randomized controlled trial conducted in 16 primary care practices assessing the efficacy of AF rhythm assessment with single-lead electrocardiogram in routine care. Patients 65 years and older were offered rhythm assessment at visits. In this secondary analysis, we evaluated rhythm assessment uptake and compared initiation and discontinuation of OAC in patients with previously diagnosed AF from intervention and control arms over 1 year. Results: The study included 4593 patients with previously diagnosed AF (2250 intervention; 2343 control). In the intervention arm, 2022 (89.9%) completed rhythm assessment (median 2 visits with rhythm assessment) and 40.1% had ≥1 "Possible AF" result. Initiation of OAC was similar in the intervention (17.7%) and control (19.1%) arms but was influenced by the rhythm assessment result: higher with a "Possible AF" (26.1%; adjusted odds ratio [aOR] 1.62; 95% confidence interval [CI] 1.04-2.51), and lower with a "Normal" result (9.9%; aOR 0.45; 95% CI 0.29-0.71) compared to control. OAC discontinuation was similar in the intervention (6.3%) and control (7.2%) arms, with lower discontinuation with a "Possible AF" result (3.8%; aOR 0.51; 95% CI 0.32-0.81). Conclusions: Including patients with previously diagnosed AF in a point-of-care rhythm assessment strategy did not increase overall OAC use compared to the control arm. However, the rhythm assessment result influenced both initiation and discontinuation of OAC.

Accuracy and variability of cardiologist interpretation of single lead electrocardiograms for atrial fibrillation: The VITAL-AF trial.

BACKGROUND: Screening for atrial fibrillation (AF) using consumer-based devices capable of producing a single lead electrocardiogram (1L ECG) is increasing. There are limited data on the accuracy of physician interpretation of these tracings. The goal of this study is to assess the sensitivity, specificity, confidence, and variability of cardiologist interpretation of point-of-care 1L ECGs. METHODS: Fifteen cardiologists reviewed point-of-care handheld 1L ECGs collected from patients aged 65 years or older enrolled in the VITAL-AF clinical trial [NCT035115057] who underwent cardiac rhythm assessments with a 1L ECG using an AliveCor KardiaMobile device. Random sampling of 1L ECGs for cardiologist review was stratified by the AliveCor algorithm interpretation. A 12L ECG performed on the same day for clinical purposes was used as the gold standard. Cardiologists each reviewed a common sample of 200 1L ECG tracings and completed a survey associated with each tracing. Cardiologists were blinded to both the AliveCor algorithm and same day 12L ECG interpretation. For each tracing, study cardiologists were asked to assess the rhythm (sinus rhythm, AF, unclassifiable), report their assessment of the quality of the tracing, and rate their confidence in rhythm interpretation. The outcomes included the sensitivity, specificity, variability, and confidence in physician interpretation. Variables associated with each measure were identified using multivariable regression. RESULTS: The average sensitivity for AF was 77.4% (range 50%-90.6%, standard deviation [SD]=11.4%) and the average specificity was 73.0% (range 41.3%-94.6%, SD = 15.4%). The mean variability was 30.8% (range 0%-76.2%, SD = 23.2%). The average reviewer confidence of 1L ECG rhythm assessment was 3.6 out of 5 (range 2.5-4.2, SD = 0.6). Patient and tracing factors associated with sensitivity, specificity, variability, and confidence were identified and included age, body mass index, and presence of artifact. CONCLUSION: Cardiologist interpretation of point-of-care handheld 1L ECGs has modest diagnostic sensitivity and specificity with substantial variability for AF classification despite high confidence. Variability in cardiologist interpretation of 1L ECGs highlights the importance of confirmatory testing for diagnosing AF.

Screening for undiagnosed atrial fibrillation using a single-lead electrocardiogram at primary care visits: patient uptake and practitioner perspectives from the VITAL-AF trial.

BACKGROUND: Screening for atrial fibrillation (AF) is appealing because AF is common, when undiagnosed may increase stroke risk, and stroke is preventable with anticoagulants. This study assessed patient and primary care practitioner (PCP) acceptability of screening for AF using a 30-s single-lead electrocardiogram (SL-ECG) during outpatient visits. METHODS: Secondary analyses of a cluster randomized trial. All patients ≥ 65 years old without prevalent AF seen during a 1-year period and their PCPs. Screening using a SL-ECG was performed by medical assistants during check-in at 8 intervention sites among verbally consenting patients. PCPs were notified of "possible AF" results; management was left to their discretion. Control practices continued with usual care. Following the trial, PCPs were surveyed about AF screening. Outcomes included screening uptake and results, and PCP preferences for screening. RESULTS: Fifteen thousand three hundred ninety three patients were seen in intervention practices (mean age 73.9 years old, 59.7% female). Screening occurred at 78% of 38,502 individual encounters, and 91% of patients completed ≥ 1 screening. The positive predictive value of a "Possible AF" result (4.7% of SL-ECG tracings) at an encounter prior to a new AF diagnosis was 9.5%. Same-day 12-lead ECGs were slightly more frequent among intervention (7.0%) than control (6.2%) encounters (p = 0.07). Among the 208 PCPs completing a survey (73.6%; 78.9% intervention, 67.7% control), most favored screening for AF (87.2% vs. 83.6%, respectively), though SL-ECG screening was favored by intervention PCPs (86%) while control PCPs favored pulse palpation (65%). Both groups were less certain if AF screening should be done outside of office visits with patch monitors (47% unsure) or consumer devices (54% unsure). CONCLUSIONS: Though the benefits and harms of screening for AF remain uncertain, most older patients underwent screening and PCPs were able to manage SL-ECG results, supporting the feasibility of routine primary care screening. PCPs exposed to a SL-ECG device preferred it over pulse palpation. PCPs were largely uncertain about AF screening done outside of practice visits. TRIAL REGISTRATION: ClinicalTrials.gov NCT03515057. Registered May 3, 2018.

Screening for Atrial Fibrillation in Older Adults at Primary Care Visits: VITAL-AF Randomized Controlled Trial.

BACKGROUND: Undiagnosed atrial fibrillation (AF) may cause preventable strokes. Guidelines differ regarding AF screening recommendations. We tested whether point-of-care screening with a handheld single-lead ECG at primary care practice visits increases diagnoses of AF. METHODS: We randomized 16 primary care clinics 1:1 to AF screening using a handheld single-lead ECG (AliveCor KardiaMobile) during vital sign assessments, or usual care. Patients included were ages ≥65 years. Screening results were provided to primary care clinicians at the encounter. All confirmatory diagnostic testing and treatment decisions were made by the primary care clinician. New AF diagnoses during the 1-year follow-up were ascertained electronically and manually adjudicated. Proportions and incidence rates were calculated. Effect heterogeneity was assessed. RESULTS: Of 30 715 patients without prevalent AF (n=15 393 screening [91% screened], n=15 322 control), 1.72% of individuals in the screening group had new AF diagnosed at 1 year versus 1.59% in the control group (risk difference, 0.13% [95% CI, -0.16 to 0.42]; P=0.38). In prespecified subgroup analyses, new AF diagnoses in the screening and control groups were greater among those aged ≥85 years (5.56% versus 3.76%, respectively; risk difference, 1.80% [95% CI, 0.18 to 3.30]). The difference in newly diagnosed AF between the screening period and the previous year was marginally greater in the screening versus control group (0.32% versus -0.12%; risk difference, 0.43% [95% CI, -0.01 to 0.84]). The proportion of individuals with newly diagnosed AF who were initiated on oral anticoagulants was not different in the screening (n=194, 73.5%) and control (n=172, 70.8%) arms (risk difference, 2.7% [95% CI, -5.5 to 10.4]). CONCLUSIONS: Screening for AF using a single-lead ECG at primary care visits did not affect new AF diagnoses among all individuals aged 65 years or older compared with usual care. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03515057.

Reversal strategies and outcomes in patients with atrial fibrillation and warfarin-associated intracranial hemorrhage.

PURPOSE: Evaluate reversal strategies in atrial fibrillation (AF) patients with warfarin-associated intracranial hemorrhage (ICH) in clinical care. MATERIALS AND METHODS: Observational cohort of AF patients with warfarin-associated ICH at two referral hospitals (2007-2010), with patient features, reversal agents, and outcomes collected from medical records. RESULTS: Among 498 ICH patients 403 received fresh frozen plasma (FFP) without 3-factor prothrombin complex concentrates (PCCs) or recombinant factor VIIa (rFVIIa), 65 received PCCs or rFVIIa, mostly with FFP, and 30 received no acute reversal agents. Median time from presentation to reversal agent administration was 3.4 h (IQR 2.3-5.3). INR was reversed to ≤1.4 by 6 h post-presentation in 46% of patients receiving PCCs/rFVIIa versus 15% receiving FFP alone (p<0.0001). Among PCCs/rFVIIa recipients, 31% died in-hospital vs. 24% receiving FFP alone (p=0.27). Adjusted OR for death accounting for age and Glasgow Coma Score was 0.78 (0.36-1.69) for PCCs/rFVIIa vs FFP only and 1.16 (0.59-2.27) comparing those reaching vs. not reaching INR ≤ 1.4 at 6 h. CONCLUSIONS: Treatment with PCCs/rFVIIa led to faster INR reversal than treatment with FFP alone. Neither treatment with PCCs/rFVIIa nor rapid INR reversal was associated with improved survival. Delays receiving PCCs may largely eliminate the benefit of treatment.

Design and rationale of a pragmatic trial integrating routine screening for atrial fibrillation at primary care visits: The VITAL-AF trial.

Given the preventable morbidity and mortality associated with atrial fibrillation (AF), increased awareness of undiagnosed AF, and advances in mobile electrocardiogram (ECG) technology, there is a critical need to assess the effectiveness of using such technology to routinely screen for AF in clinical practice. VITAL-AF is a pragmatic trial that will test whether screening for AF using a single-lead handheld ECG in individuals 65 years or older during primary care visits will lead to an increased rate of AF detection. The study is a cluster-randomized trial, with 8 primary care practices randomized to AF screening and 8 primary care practices randomized to usual care. We anticipate studying approximately 16,000 patients in each arm. During the 1-year enrollment period, practice medical assistants will screen eligible patients who agree to participate during office visits using a single-lead ECG device. Automated screening results are documented in the electronic health record, and patients can discuss screening results with their provider during the scheduled visit. All single-lead ECGs are overread by a cardiologist. Screen-detected AF is managed at the discretion of the patient's physician. The primary study end point is incident AF during the screening period. Key secondary outcomes include new oral anticoagulation prescriptions, incident ischemic stroke, and major hemorrhage during a 24-month period following the study start. Outcomes are ascertained based on electronic health record documentation and are manually adjudicated. The results of this pragmatic trial may help identify a model for widespread adoption of AF screening as part of routine clinical practice.

Changes in Use of Anticoagulation in Patients With Atrial Fibrillation Within a Primary Care Network Associated With the Introduction of Direct Oral Anticoagulants.

Atrial fibrillation (AF) and the decision to anticoagulate is a common problem faced by primary care physicians. Oral anticoagulation (OAC) is underused, despite its clear benefits with regard to stroke prevention. We examined OAC usage between 2010 and 2015, following the introduction of direct oral anticoagulants (DOACs) and specifically assessed whether more patients were anticoagulated over time. The study cohort included adult patients aged 18 and older with AF cared for in an 18-practice primary care network between 2010 and 2015. AF status was assigned each calendar year using a validated electronic health record algorithm. We examined OAC usage over time in all patients with AF, and in patients at high risk of stroke (CHA2DS2-VASc ≥ 2). The proportion of the population with AF increased over time (2010: 4,920 patients [3.5%], 2015: 6,452 patients [4.0%]). There was no increase in the proportion of patients prescribed any OAC treatment from 2010 (57.0%) to 2015 (57.4%) (p = 0.41). Similarly, in patients at high risk of stroke, the proportion anticoagulated did not increase over time (2010: 61.1%, 2015: 61.7%, p = 0.51). Over the study period, DOAC usage increased from 0.31% of all patients with AF in 2010 to 18.3% in 2015 (p < 0.001). Patients prescribed DOACs were younger, with lower risk of stroke. In conclusion, this study showed an increasing proportion of patients with AF over time in a primary care network. The use of DOACs increased over time; however, the proportion of patients treated with OAC did not increase over time.

First Diagnosis of Atrial Fibrillation at the Time of Stroke.

BACKGROUND: Atrial fibrillation (AF) is a major cause of ischemic stroke. Individuals with undiagnosed AF lack the stroke protection afforded by oral anticoagulants. We obtained a contemporary estimate of the percentage of AF patients newly diagnosed at the time of stroke. METHODS: We identified patients admitted to the Massachusetts General Hospital (MGH) from January 1, 2010 to December 31, 2013 with acute ischemic stroke and either previously or newly diagnosed AF using hospital stroke registry data and stroke and AF ICD-9 code searches of hospital databases. Reviewers categorized AF as previously known or newly diagnosed, and collected comorbidity and outcome data. To confirm AF as newly diagnosed, we searched patients' pre-event electronic medical records (EMRs) for AF terms. RESULTS: AF was considered newly diagnosed in 156/856 patients (18%; 95% CI 16-21). In 136/156 cases, AF was diagnosed using 12-lead EKG, telemetry, or rhythm strips. New AF strokes had a median NIH stroke scale of 12; 60% had mRankin ≥3 at discharge, including 15% deaths. Pre-stroke CHA2DS2-VASc score was ≥2 in 89%. About half (76/156) had prior records in the MGH EMR. Evidence of pre-stroke AF, often peri-procedural, was found in 8/76, but the AF diagnosis was not carried forward. CONCLUSIONS: In this contemporary cohort, nearly one in 5 AF-related strokes occurred without a pre-stroke AF diagnosis. AF was readily diagnosed using standard rhythm monitoring. The vast majority of patients with newly diagnosed AF were at high enough pre-stroke risk to merit anticoagulation. In conclusion, our findings support screening for AF before stroke. Patients with past transient AF may merit more intensive screening.

Use of Oral Anticoagulant Therapy in Older Adults with Atrial Fibrillation After Acute Ischemic Stroke.

OBJECTIVES: To explore barriers to anticoagulation in older adults with atrial fibrillation (AF) at high risk of stroke and to identify opportunities for interventions that might increase use of oral anticoagulants (OACs). DESIGN: Retrospective cohort study. SETTING: Two large community-based AF cohorts. PARTICIPANTS: Individuals with ischemic stroke surviving hospitalization (N = 1,405, mean age 79). MEASUREMENTS: Using structured chart review, reasons for nonuse of OAC were identified, and 1-year poststroke survival was assessed. Logistic regression was used to identify correlates of OAC nonuse. RESULTS: Median CHA2 DS2 -VASc score was 5, yet 44% of participants were not prescribed an OAC at discharge. The most-frequent (nonmutually exclusive) physician reasons for not prescribing OAC included fall risk (26.7%), poor prognosis (19.3%), bleeding history (17.1%), participant or family refusal (14.9%), older age (11.0%), and dementia (9.4%). Older age (odds ratio (OR) = 8.96, 95% confidence interval (CI) = 5.01-16.04 for aged ≥85 vs <65) and disability (OR = 12.58, 95% CI = 5.82-27.21 for severe vs no deficit) were the most-important independent predictors of nonuse of OACs. By 1 year, 42.5% of those not receiving an OAC at discharge had died, versus 19.1% of those receiving an OAC (P < .001), far higher than recurrent stroke rates. CONCLUSION: Despite very high stroke risk, more than 40% of participants were not discharged with an OAC. Dominant reasons included fall risk, poor prognosis, older age, and dementia. These individuals' high 1-year mortality rate confirmed their high level of comorbidity. To improve anticoagulation decisions and outcomes in this population, future research should focus on strategies to mitigate fall risk, improve assessment of risks and benefits of anticoagulation in individuals with AF, and determine whether newer anticoagulants are safer in complex elderly and frail individuals.

How Well Do Stroke Risk Scores Predict Hemorrhage in Patients With Atrial Fibrillation?

The decision to use anticoagulants for atrial fibrillation depends on comparing a patient's estimated risk of stroke to their bleeding risk. Several of the risk factors in the stroke risk schemes overlap with hemorrhage risk. We compared how well 2 stroke risk scores (CHADS2 and CHA2DS2-VASc) and 2 hemorrhage risk scores (the ATRIA bleeding score and the HAS-BLED score) predicted major hemorrhage on and off warfarin in a cohort of 13,559 community-dwelling adults with AF. Over a cumulative 64,741 person-years of follow-up, we identified a total of 777 incident major hemorrhage events. The ATRIA bleeding score had the highest predictive ability of all the scores in patients on warfarin (c-index of 0.74 [0.72 to 0.76] compared with 0.65 [0.62 to 0.67] for CHADS2, 0.65 [0.62 to 0.67] for CHA2DS2-VASc, and 0.64 [0.61 to 0.66] for HAS-BLED) and in those off warfarin (0.77 [0.74 to 0.79] compared with 0.67 [0.64 to 0.71] for CHADS2, 0.67 [0.64 to 0.70] for CHA2DS2-VASc, and 0.68 [0.65 to 0.71] for HAS-BLED). In conclusion, although CHADS2 and CHA2DS2-VASc stroke scores were better at predicting hemorrhage than chance alone, they were inferior to the ATRIA bleeding score. Our study supports the use of dedicated hemorrhage risk stratification tools to predict major hemorrhage in atrial fibrillation.

Stability of High-Quality Warfarin Anticoagulation in a Community-Based Atrial Fibrillation Cohort: The Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study.

BACKGROUND: Warfarin reduces ischemic stroke risk in atrial fibrillation (AF) but increases bleeding risk. Novel anticoagulants challenge warfarin as stroke-preventive therapy for AF. They are available at fixed doses but are more costly. Warfarin anticoagulation at a time in therapeutic range (TTR) ≥70% is similarly as effective and safe as novel anticoagulants. It is unclear whether AF patients with TTR ≥70% will remain stably anticoagulated and avoid the need to switch to a novel anticoagulant. We assessed stability of warfarin anticoagulation in AF patients with an initial TTR ≥70%. METHODS AND RESULTS: Within the community-based Anticoagulation and Risk Factors in AF (ATRIA) cohort followed from 1996 to 2003, we identified 2841 new warfarin users who continued warfarin over 9 months. We excluded months 1 to 3 to achieve a stable dose. For the 987 patients with TTR ≥70% in an initial 6-month period (TTR1; months 4-9), we described the distribution of TTR2 (months 10-15) and assessed multivariable correlates of persistent TTR ≥70%. Of patients with TTR1 ≥70%, 57% persisted with TTR2 ≥70% and 16% deteriorated to TTR2 <50%. Only initial TTR1 ≥90% (adjusted odds ratio 1.47, 95% CI 1.07-2.01) independently predicted TTR2 ≥70%. Heart failure was moderately associated with marked deterioration (TTR2 <50%); adjusted odds ratio 1.45, 95% CI 1.00-2.10. CONCLUSIONS: Nearly 60% of AF patients with high-quality TTR1 on warfarin maintained TTR ≥70% over the next 6 months. A minority deteriorated to very poor TTR. Patient features did not strongly predict TTR in the second 6-month period. Our analyses support watchful waiting for AF patients with initial high-quality warfarin anticoagulation before considering alternative anticoagulants.

Randomized trial of a health IT tool to support between-visit-based laboratory monitoring for chronic disease medication prescriptions.

BACKGROUND: Lack of timely medication intensification and inadequate medication safety monitoring are two prevalent and potentially modifiable barriers to effective and safe chronic care. Innovative applications of health information technology tools may help support chronic disease management. OBJECTIVE: To examine the clinical impact of a novel health IT tool designed to facilitate between-visit ordering and tracking of future laboratory testing. DESIGN AND PARTICIPANTS: Clinical trial randomized at the provider level (n = 44 primary care physicians); patient-level outcomes among 3,655 primary care patients prescribed 5,454 oral medicines for hyperlipidemia, diabetes, and/or hypertension management over a 12-month period. MAIN MEASURES: Time from prescription to corresponding follow-up laboratory testing; proportion of follow-up time that patients achieved corresponding risk factor control (A1c, LDL); adverse event laboratory monitoring 4 weeks after medicine prescription. KEY RESULTS: Patients whose physicians were allocated to the intervention (n = 1,143) had earlier LDL laboratory assessment compared to similar patients (n = 703) of control physicians [adjusted hazard ratio (aHR): 1.15 (1.01-1.32), p = 0.04]. Among patients with elevated LDL (486 intervention, 324 control), there was decreased time to LDL goal in the intervention group [aHR 1.26 (0.99-1.62)]. However, overall there were no significant differences between study arms in time spent at LDL or HbA1c goal. Follow-up safety monitoring (e.g., creatinine, potassium, or transaminases) was relatively infrequent (ranging from 7 % to 29 % at 4 weeks) and not statistically different between arms. Intervention physicians indicated that lack of reimbursement for non-visit-based care was a barrier to use of the tool. CONCLUSIONS: A health IT tool to support between-visit laboratory monitoring improved the LDL testing interval but not LDL or HbA1c control, and it did not alter safety monitoring. Adoption of innovative tools to support physicians in non-visit-based chronic disease management may be limited by current visit-based financial and productivity incentives.

Digoxin and risk of death in adults with atrial fibrillation: the ATRIA-CVRN study.

BACKGROUND: Digoxin remains commonly used for rate control in atrial fibrillation, but limited data exist supporting this practice and some studies have shown an association with adverse outcomes. We examined the independent association between digoxin and risks of death and hospitalization in adults with incident atrial fibrillation and no heart failure. METHODS AND RESULTS: We performed a retrospective cohort study of 14,787 age, sex, and high-dimensional propensity score-matched adults with incident atrial fibrillation and no previous heart failure or digoxin use in the AnTicoagulation and Risk factors In Atrial fibrillation-Cardiovascular Research Network (ATRIA-CVRN) study within Kaiser Permanente Northern and Southern California. We examined the independent association between newly initiated digoxin and the risks of death and hospitalization using extended Cox regression. During a median 1.17 (interquartile range, 0.49-1.97) years of follow-up among matched patients with atrial fibrillation, incident digoxin use was associated with higher rates of death (8.3 versus 4.9 per 100 person-years; P<0.001) and hospitalization (60.1 versus 37.2 per 100 person-years; P<0.001). Incident digoxin use was independently associated with a 71% higher risk of death (hazard ratio, 1.71; 95% confidence interval, 1.52-1.93) and a 63% higher risk of hospitalization (hazard ratio, 1.63; 95% confidence interval, 1.56-1.71). Results were consistent in subgroups of age and sex and when using intent-to-treat or on-treatment analytic approaches. CONCLUSIONS: In adults with atrial fibrillation, digoxin use was independently associated with higher risks of death and hospitalization. Given other available rate control options, digoxin should be used with caution in the management of atrial fibrillation.

Effect of selective serotonin reuptake inhibitors on bleeding risk in patients with atrial fibrillation taking warfarin.

Selective serotonin reuptake inhibitor (SSRI) medications have been linked to increased bleeding risk; however, the actual association among warfarin, SSRI exposure, and bleeding risk has not been well-established. We studied the AnTicoagulation and Risk factors In Atrial fibrillation cohort of 13,559 adults with atrial fibrillation, restricted to the 9,186 patients contributing follow-up time while taking warfarin. Exposure to SSRIs and tricyclic antidepressants (TCAs) was assessed from pharmacy database dispensing data. The main outcome was hospitalization for major hemorrhage. Results were adjusted for bleeding risk and time in international normalized ratio range >3. We identified 461 major hemorrhages during 32,888 person-years of follow-up, 45 events during SSRI use, 12 during TCA-only use, and 404 without either medication. Hemorrhage rates were higher during periods of SSRI exposure compared with periods on no antidepressants (2.32 per 100 person-years vs 1.35 per 100 person-years, p <0.001) and did not differ between TCA exposure and no antidepressants (1.30 per 100 person-years on TCAs, p = 0.94). After adjustment for underlying bleeding risk and time in international normalized ratio range >3, SSRI exposure was associated with an increased rate of hemorrhage compared with no antidepressants (adjusted relative risk 1.41, 95% confidence interval 1.04 to 1.92, p = 0.03), whereas TCA exposure was not (adjusted relative risk 0.82, 95% confidence interval 0.46 to 1.46, p = 0.50). In conclusion, SSRI exposure was associated with higher major hemorrhage risk in patients taking warfarin, and this risk should be considered when selecting antidepressant treatments in those patients.

Long-term survival after ischemic stroke in patients with atrial fibrillation.

OBJECTIVES: While the short-term impact of atrial fibrillation-related stroke has been well studied, surprisingly little is known about its long-term effect on survival. METHODS: We followed 13,559 patients with atrial fibrillation for a median of 6 years, identifying ischemic strokes through computerized databases and validating 1,025 events. Stroke severity was determined from hospital records. We compared survival of stroke patients with comparator nonstroke patients (matched for age, sex, race, comorbid conditions, and time of entry into the cohort) using proportional hazard models controlling for warfarin use and compared survival by degree of discharge deficit. RESULTS: Median survival after stroke was 1.8 years compared with 5.7 years for matched nonstroke comparators (hazard ratio [HR] 2.8, 95% confidence interval [CI] 2.5-3.2). This increased risk of all-cause death persisted even after restricting the analysis to the 576 stroke patients who survived 6 months after the initial stroke event (HR 2.0, 95% CI 1.7-2.5, adjusting for warfarin use). Risk of death was strongly associated with stroke severity: HR 2.9 (95% CI 2.3-3.5) for strokes resulting in major deficits and HR 8.3 (95% CI 5.2-13.2) for strokes resulting in severe deficits compared with matched comparators without stroke. CONCLUSIONS: Ischemic stroke approximately triples the mortality rate in patients with atrial fibrillation. This effect persists well beyond the immediate period poststroke and is strongly associated with disability after stroke. Stroke prevention by anticoagulation has even greater beneficial effects on survival than usually considered when focusing solely on 30-day mortality rates.

A new risk scheme to predict ischemic stroke and other thromboembolism in atrial fibrillation: the ATRIA study stroke risk score.

BACKGROUND: More accurate and reliable stroke risk prediction tools are needed to optimize anticoagulation decision making in patients with atrial fibrillation (AF). We developed a new AF stroke prediction model using the original Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) AF cohort and externally validated the score in a separate, contemporary, community-based inception AF cohort, ATRIA-Cardiovascular Research Network (CVRN) cohort. METHODS AND RESULTS: The derivation ATRIA cohort consisted of 10 927 patients with nonvalvular AF contributing 32 609 person-years off warfarin and 685 thromboembolic events (TEs). The external validation ATRIA-CVRN cohort included 25 306 AF patients contributing 26 263 person-years off warfarin and 496 TEs. Cox models identified 8 variables, age, prior stroke, female sex, diabetes mellitus, heart failure, hypertension, proteinuria, and eGFR<45 mL/min per 1.73 m(2) or end-stage renal disease, plus an age×prior stroke interaction term for the final model. Point scores were assigned proportional to model coefficients. The c-index in the ATRIA cohort was 0.73 (95% CI, 0.71 to 0.75), increasing to 0.76 (95% CI, 0.74 to 0.79) when only severe events were considered. In the ATRIA-CVRN, c-indexes were 0.70 (95% CI, 0.67 to 0.72) and 0.75 (95% CI, 0.72 to 0.78) for all events and severe events, respectively. The C-index was greater and net reclassification improvement positive comparing the ATRIA score with the CHADS2 or CHA2DS2-VASc scores. CONCLUSIONS: The ATRIA stroke risk score performed better than existing risk scores, was validated successfully, and showed improvement in predicting severe events, which is of greatest concern. The ATRIA score should improve the antithrombotic decision for patients with AF and should provide a secure foundation for the addition of biomarkers in future prognostic models.

Thirty-day mortality after ischemic stroke and intracranial hemorrhage in patients with atrial fibrillation on and off anticoagulants.

BACKGROUND AND PURPOSE: Prescribing warfarin for atrial fibrillation depends in large part on the expected reduction in ischemic stroke risk versus the expected increased risk of intracranial hemorrhage (ICH). However, the anticoagulation decision also depends on the relative severity of such events. We assessed the impact of anticoagulation on 30-day mortality from ischemic stroke versus ICH in a large community-based cohort of patients with atrial fibrillation. METHODS: We followed 13,559 patients with atrial fibrillation enrolled in an integrated healthcare delivery system for a median 6 years. Incident ischemic strokes and ICHs were identified from computerized databases and validated through medical record review. The association of warfarin and international normalized ratio at presentation with 30-day mortality was modeled using multivariable logistic regression adjusting for clinical factors. RESULTS: We identified 1025 incident ischemic strokes and 299 ICHs during follow-up. Compared with no antithrombotic therapy, warfarin was associated with reduced Rankin score and lower 30-day mortality from ischemic stroke (adjusted OR, 0.64; 95% CI, 0.45-0.91) but a higher mortality from ICH (OR, 1.62; 95% CI, 0.88-2.98). Therapeutic international normalized ratios (2-3) were associated with an especially low ischemic stroke mortality (OR, 0.38; 95% CI, 0.20-0.70), whereas international normalized ratios>3 increased the odds of dying of ICH by 2.66-fold (95% CI, 1.21-5.86). CONCLUSIONS: Warfarin reduces 30-day mortality from ischemic stroke but increases ICH-related mortality. Both effects on event severity as well as on event rates need to be incorporated into rational decision-making about anticoagulants for atrial fibrillation.