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Anxiety, Depression, and Adverse Clinical Outcomes in Patients With Atrial Fibrillation Starting Warfarin: Cardiovascular Research Network WAVE Study.

ABSTRACT: Anxiety and depression are associated with worse outcomes in several cardiovascular conditions, but it is unclear whether they affect outcomes in atrial fibrillation (AF). In a large diverse population of adults with AF, we evaluated the association of diagnosed anxiety and/or depression with stroke and bleeding outcomes.The Cardiovascular Research Network WAVE (Community-Based Control and Persistence of Warfarin Therapy and Associated Rates and Predictors of Adverse Clinical Events in Atrial Fibrillation and Venous Thromboembolism) Study included adults with AF newly starting warfarin between 2004 and 2007 within 5 health delivery systems in the United States. Diagnosed anxiety and depression and other patient characteristics were identified from electronic health records. We identified stroke and bleeding outcomes from hospitalization databases using validated International Classification of Diseases, Ninth Revision (ICD-9), codes. We used multivariable Cox regression to assess the relation between anxiety and/or depression with outcomes after adjustment for stroke and bleeding risk factors. In 25 570 adults with AF initiating warfarin, 490 had an ischemic stroke or intracranial hemorrhage (1.52 events per 100 person-years). In multivariable analyses, diagnosed anxiety was associated with a higher adjusted rate of combined ischemic stroke and intracranial hemorrhage (hazard ratio, 1.52; 95% confidence interval, 1.01-2.28). Results were not materially changed after additional adjustment for patient-level percentage of time in therapeutic anticoagulation range on warfarin (hazard ratio, 1.56; 95% confidence interval, 1.03-2.36). In contrast, neither isolated depression nor combined depression and anxiety were significantly associated with outcomes.Diagnosed anxiety was independently associated with increased risk of combined ischemic stroke and intracranial hemorrhage in adults with AF initiating warfarin that was not explained by differences in risk factors or achieved anticoagulation quality.

SUBMITTER: Baumgartner C

PROVIDER: S-EPMC6015441 | biostudies-other | 2018 Apr

REPOSITORIES: biostudies-other

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Anxiety, Depression, and Adverse Clinical Outcomes in Patients With Atrial Fibrillation Starting Warfarin: Cardiovascular Research Network WAVE Study.

Baumgartner Christine C Fan Dongjie D Fang Margaret C MC Singer Daniel E DE Witt Daniel M DM Schmelzer John R JR Williams Marc S MS Gurwitz Jerry H JH Sung Sue Hee SH Go Alan S AS

Journal of the American Heart Association 20180414 8

<h4>Background</h4>Anxiety and depression are associated with worse outcomes in several cardiovascular conditions, but it is unclear whether they affect outcomes in atrial fibrillation (AF). In a large diverse population of adults with AF, we evaluated the association of diagnosed anxiety and/or depression with stroke and bleeding outcomes.<h4>Methods and results</h4>The Cardiovascular Research Network WAVE (Community-Based Control and Persistence of Warfarin Therapy and Associated Rates and Pre ...[more]

PMID: 29656278

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Project description:ObjectiveTo determine rates of major bleeding by level of kidney function for older adults with atrial fibrillation starting warfarin.DesignRetrospective cohort study.SettingCommunity based, using province wide laboratory and administrative data in Alberta, Canada.Participants12,403 adults aged 66 years or more, with atrial fibrillation who started warfarin treatment between 1 May 2003 and 31 March 2010 and had a measure of kidney function at baseline. Kidney function was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation and participants were categorised based on estimated glomerular filtration rate (eGFR): ? 90, 60-89, 45-59, 30-44, 15-29, <15 mL/min/1.73 m(2). We excluded participants with end stage renal disease (dialysis or renal transplant) at baseline.Main outcome measuresAdmission to hospital or visit to an emergency department for major bleeding (intracranial, upper and lower gastrointestinal, or other).ResultsOf 12,403 participants, 45% had an eGFR <60 mL/min/1.73 m(2). Overall, 1443 (11.6%) experienced a major bleeding episode over a median follow-up of 2.1 (interquartile range: 1.0-3.8) years. During the first 30 days of warfarin treatment, unadjusted and adjusted rates of major bleeding were higher at lower eGFR (P for trend <0.001 and 0.001, respectively). Adjusted bleeding rates per 100 person years were 63.4 (95% confidence interval 24.9 to 161.6) in participants with eGFR <15 mL/min/1.73 m(2) compared with 6.1 (1.9 to 19.4) among those with eGFR >90 mL/min/1.73 m(2) (adjusted incidence rate ratio 10.3, 95% confidence interval 2.3 to 45.5). Similar associations were observed at more than 30 days after starting warfarin, although the magnitude of the increase in rates across eGFR categories was attenuated. Across all eGFR categories, adjusted rates of major bleeding were consistently higher during the first 30 days of warfarin treatment compared with the remainder of follow-up. Increases in major bleeding rates were largely due to gastrointestinal bleeding (3.5-fold greater in eGFR <15 mL/min/1.73 m(2) compared with ? 90 mL/min/1.73 m(2)). Intracranial bleeding was not increased with worsening kidney function.ConclusionsReduced kidney function was associated with an increased risk of major bleeding among older adults with atrial fibrillation starting warfarin; excess risks from reduced eGFR were most pronounced during the first 30 days of treatment. Our results support the need for careful consideration of the bleeding risk relative to kidney function when assessing the risk-benefit ratio of warfarin treatment in people with chronic kidney disease and atrial fibrillation, particularly in the first 30 days of treatment.

Project description:Atrial fibrillation (AF) is the most common cardiac rhythm disorder with a significant health burden. The aim of this study was to characterise patients with recently diagnosed AF and to estimate the rates of comorbidities and outcome events requiring hospitalisation in routine clinical practice.Pharmacoepidemiological cohort study using observational data.This study included 16 513 patients with a first diagnosis of AF between 1 January 2005 and 28 February 2010 (newly diagnosed patients) using data from the UK Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics (HES) and the Office for National Statistics mortality data. Exposure was stratified by vitamin K antagonist (VKA) exposure (non-use, current, recent and past exposure) based on prescriptions and/or international normalised ratio measurements, and followed for outcome events of interest based on diagnosis codes in the databases, that is, vascular outcomes, bleeding events and others. The main focus of the study was on outcome events requiring hospitalisation using the HES data.The incidence of vascular outcome hospitalisations (myocardial infarction (MI), stroke or systemic arterial peripheral embolism) was 3.8 (95% CI 3.5 to 4.0)/100 patient-years. The incidence of stroke was 0.9 (0.8 to 1.1) during current VKA exposure, 2.2 (1.6 to 2.9) for recent, 2.4 (1.9 to 2.9) for past and 3.4 (3.1 to 3.7) during non-use. MI incidence was 0.7 (0.6 to 0.9) for current VKA exposure, 0.7 (0.4 to 1.2) for recent, 1.1 (0.8 to 1.5) for past and 1.9 (1.7 to 2.1) during non-use. The incidence of bleeding event hospitalisations was 3.8 (3.4 to 4.2) for current VKA exposure, 4.5 (3.7 to 5.5) for recent, 2.7 (2.2 to 3.3) for past and 2.9 (2.6 to 3.2) during non-use; 38% of intracranial bleeds and 6% of gastrointestinal bleeds were fatal.This population-based study from recent years provides a comprehensive characterisation of newly diagnosed patients with AF and incidence estimates of common outcomes with a focus on hospitalised events stratified by VKA exposure. This study will help to place future data on new oral anticoagulants into perspective.

Project description:BackgroundAlthough warfarin has been extensively studied in clinical trials, little is known about rates of hemorrhage attributable to its use in routine clinical practice. Our objective was to examine incident hemorrhagic events in a large population-based cohort of patients with atrial fibrillation who were starting treatment with warfarin.MethodsWe conducted a population-based cohort study involving residents of Ontario (age ≥ 66 yr) with atrial fibrillation who started taking warfarin between Apr. 1, 1997, and Mar. 31, 2008. We defined a major hemorrhage as any visit to hospital for hemorrage. We determined crude rates of hemorrhage during warfarin treatment, overall and stratified by CHADS(2) score (congestive heart failure, hypertension, age ≥ 75 yr, diabetes mellitus and prior stroke, transient ischemic attack or thromboembolism).ResultsWe included 125 195 patients with atrial fibrillation who started treatment with warfarin during the study period. Overall, the rate of hemorrhage was 3.8% (95% confidence interval [CI] 3.8%-3.9%) per person-year. The risk of major hemorrhage was highest during the first 30 days of treatment. During this period, rates of hemorrhage were 11.8% (95% CI 11.1%-12.5%) per person-year in all patients and 16.7% (95% CI 14.3%-19.4%) per person-year among patients with a CHADS(2) scores of 4 or greater. Over the 5-year follow-up, 10 840 patients (8.7%) visited the hospital for hemorrhage; of these patients, 1963 (18.1%) died in hospital or within 7 days of being discharged.InterpretationIn this large cohort of older patients with atrial fibrillation, we found that rates of hemorrhage are highest within the first 30 days of warfarin therapy. These rates are considerably higher than the rates of 1%-3% reported in randomized controlled trials of warfarin therapy. Our study provides timely estimates of warfarin-related adverse events that may be useful to clinicians, patients and policy-makers as new options for treatment become available.

Project description:BackgroundGuidelines recommend warfarin use in patients with atrial fibrillation solely on the basis of risk for ischemic stroke without antithrombotic therapy. These guidelines rely on ischemic stroke rates observed in older trials and do not explicitly account for increased risk for hemorrhage.ObjectiveTo quantify the net clinical benefit of warfarin therapy in a cohort of patients with atrial fibrillation.DesignMixed retrospective and prospective cohort study of patients with atrial fibrillation between 1996 and 2003.SettingAn integrated health care delivery system.Patients13 559 adults with nonvalvular atrial fibrillation.MeasurementsWarfarin exposure, patient characteristics, CHADS(2) score (1 point for each of congestive heart failure, hypertension, age, and diabetes and 2 points for stroke), and outcome events were ascertained from health plan records and databases. Net clinical benefit was defined as the annual rate of ischemic strokes and systemic emboli prevented by warfarin minus intracranial hemorrhages attributable to warfarin, multiplied by an impact weight. The base-case impact weight was 1.5, reflecting the greater clinical impact of intracranial hemorrhage versus thromboembolism.ResultsPatients accumulated more than 66 000 person-years of follow-up. The adjusted net clinical benefit of warfarin for the cohort overall was 0.68% per year (95% CI, 0.34% to 0.87%). Adjusted net clinical benefit was greatest for patients with a history of ischemic stroke (2.48% per year [CI, 0.75% to 4.22%]) and for those 85 years or older (2.34% per year [CI, 1.29% to 3.30%]). The net clinical benefit of warfarin increased from essentially zero in CHADS(2) stroke risk categories 0 and 1 to 2.22% per year (CI, 0.58% to 3.75%) in CHADS(2) categories 4 to 6. The patterns of results were preserved when weighting factors for intracranial hemorrhage of 1.0 and 2.0 were used.LimitationsResidual confounding is a possibility. Some outcome events were probably missed by the screening algorithm or when medical records were unavailable.ConclusionExpected net clinical benefit of warfarin therapy is highest among patients with the highest untreated risk for stroke, which includes the oldest age category. Risk assessment that incorporates both risk for thromboembolism and risk for intracranial hemorrhage provides a more quantitatively informed basis for the decision on antithrombotic therapy in patients with atrial fibrillation.Primary funding sourceNational Institute on Aging; National Heart, Lung, and Blood Institute; and Massachusetts General Hospital.

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Anxiety, Depression, and Adverse Clinical Outcomes in Patients With Atrial Fibrillation Starting Warfarin: Cardiovascular Research Network WAVE Study.

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Anxiety, Depression, and Adverse Clinical Outcomes in Patients With Atrial Fibrillation Starting Warfarin: Cardiovascular Research Network WAVE Study.

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