Dataset Information

The Association Between Bleeding and the Incidence of Warfarin Discontinuation in Patients with Atrial Fibrillation.

ABSTRACT:

Aim

While bleeding is a well-known complication of warfarin use and is thought to be a contributory cause of treatment discontinuation, studies quantifying this association are limited. The objective of this study was to quantify the association between bleeding events and subsequent warfarin discontinuation in patients with nonvalvular atrial fibrillation (NVAF).

Methods

A nested case-control analysis was conducted within a cohort of patients with NVAF newly treated with warfarin. All patients who discontinued warfarin (at least 60 days from last day of warfarin supply) during follow-up were identified as cases and matched with up to 10 controls on age, sex, and duration of follow-up. The index date was defined as the date of warfarin treatment discontinuation of the cases. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of warfarin treatment discontinuation associated with a bleeding event in the 60 days before the index date.

Results

The cohort included 24,243 patients who initiated warfarin treatment, of whom 13,482 discontinued treatment during follow-up (cases). Bleeding was associated with an increased risk of warfarin treatment discontinuation (3.55% vs. 0.85%; OR, 4.31; 95% CI, 3.87-4.81). When including only bleeds as the first listed diagnosis, the unadjusted OR was 4.64 (95% CI, 4.10-5.26), and the adjusted OR was 4.65 (95% CI, 4.10-5.27).

Conclusions

Bleeding was significantly associated with warfarin discontinuation, and thus, the selection of an effective treatment regimen associated with a lower bleeding rate could be a desirable treatment approach.

SUBMITTER: Simon TA

PROVIDER: S-EPMC4849207 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Association Between Bleeding and the Incidence of Warfarin Discontinuation in Patients with Atrial Fibrillation.

Simon Teresa A TA Pan Xianying X Kawabata Hugh H Huang Han-Yao HY Azoulay Laurent L

Cardiovascular therapeutics 20160401 2

<h4>Aim</h4>While bleeding is a well-known complication of warfarin use and is thought to be a contributory cause of treatment discontinuation, studies quantifying this association are limited. The objective of this study was to quantify the association between bleeding events and subsequent warfarin discontinuation in patients with nonvalvular atrial fibrillation (NVAF).<h4>Methods</h4>A nested case-control analysis was conducted within a cohort of patients with NVAF newly treated with warfarin ...[more]

PMID: 26763662

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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:Traumatic intracranial bleeding, which is most commonly attributable to falls, is a common concern among health care professionals, who are hesitant to prescribe oral anticoagulants to older adults with atrial fibrillation.To describe the incidence of and risk factors for traumatic intracranial bleeding in a large cohort of older adults who were newly prescribed warfarin sodium.Retrospective cohort study at the US Department of Veterans Affairs (VA). Participants included 31?951 veterans with atrial fibrillation 75 years or older who were new referrals to VA anticoagulation clinics (for warfarin therapy) between January 1, 2002, and December 31, 2012. The dates of the core analysis were March 2014 through May 2015, and subsequent ad hoc analyses were performed through December 2015. Patients with comorbid conditions requiring warfarin were excluded.The primary outcome was hospitalization for traumatic intracranial bleeding. Secondary outcomes included hospitalization for any intracranial bleeding or ischemic stroke. We used International Classification of Diseases, Ninth Revision, Clinical Modification codes to identify the incidence rates of these outcomes after warfarin initiation using VA administrative data (in-system hospitalizations) and Medicare fee-for-service claims data (out-of-system hospitalizations). Clinical characteristics, laboratory results, and pharmacy data were extracted from the VA electronic medical record. For traumatic intracranial bleeding, Cox proportional hazards regression was used to determine predictors of interest selected a priori based on prior known associations.The study population comprised 31?951 participants. The mean (SD) patient age was 81.1 (4.1) years, and 98.1% were male. Comorbidities were common, including hypertension (82.5%), coronary artery disease (42.6%), and diabetes mellitus (33.8%). During the study period, the incidence rate of hospitalization for traumatic intracranial bleeding was 4.80 per 1000 person-years. In unadjusted models, significant predictors of traumatic intracranial bleeding included dementia, fall within the past year, anemia, depression, abnormal renal or liver function, anticonvulsant use, labile international normalized ratio, and antihypertensive use. After adjusting for potential confounders, the remaining significant predictors for traumatic intracranial bleeding were dementia (hazard ratio [HR], 1.76; 95% CI, 1.26-2.46), anemia (HR, 1.23; 95% CI, 1.00-1.52), depression (HR, 1.30; 95% CI, 1.05-1.61), anticonvulsant use (HR, 1.35; 95% CI, 1.04-1.75), and labile international normalized ratio (HR, 1.33; 95% CI, 1.04-1.72). The incidence rates of hospitalization for any intracranial bleeding and ischemic stroke were 14.58 and 13.44, respectively, per 1000 person-years.Among patients 75 years or older with atrial fibrillation initiating warfarin therapy, the risk factors for traumatic intracranial bleeding are unique from those for ischemic stroke. The high overall rate of intracranial bleeding in our sample supports the need to more systematically evaluate the benefits and harms of warfarin therapy in older adults.

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:Background:Given the lack of clear indications for the use of warfarin in the treatment of atrial fibrillation (AF) in patients on hemodialysis and the potential risks that accompany warfarin use in these patients, we systematically reviewed stroke and bleeding outcomes in hemodialysis patients treated with warfarin for AF. Objective:To systematically review the stroke and bleeding outcomes associated with warfarin use in the hemodialysis population to treat AF. Design:Systematic review. Setting:All adult hemodialysis patients. Patients:Patients on hemodialysis receiving warfarin for the management of AF. Measurements:Any type of stroke and/or bleeding outcomes. Methods:MEDLINE(R) In-Process & Other Non-Indexed Citations and MEDLINE(R) via OVID (1946 to January 11, 2017), and EMBASE via OVID (1974 to January 11, 2017) were searched for relevant literature. Inclusion criteria were randomized controlled trials, observational studies, and case series in English that examined stroke and bleeding outcomes in adult population of patients (over 18 years old) who are on hemodialysis and taking warfarin for AF. Studies with less than 10 subjects, case reports, review articles, and editorials were excluded. Quality of selected articles was assessed using Newcastle-Ottawa Scale (NOS). Results:Of the 2340 titles and abstracts screened, 7 met the inclusion criteria. Two studies showed an association between warfarin use and an increased risk of stroke (Hazard Ratio: 1.93-3.36) but no association with an increased risk of bleed (HR: 0.85-1.04), while 4 studies showed no association between warfarin and stroke outcomes (HR: 0.12-1.17) but identified an association between warfarin and increased bleeding outcome (HR: 1.41-3.96). And 1 study reported neither beneficial nor harmful effects associated with warfarin use. Limitations:The major limitation to this review is that the 7 included studies were observational cohort studies, and thus the outcome measures were not specified and predetermined in a research protocol. Conclusion:Our systematic review demonstrated that for patients with AF who are on hemodialysis, warfarin was not associated with reduced outcomes of stroke but was rather associated with increased bleeding events.

Project description:ImportanceBleeding and thrombotic events (eg, stroke and systemic embolism) are common in patients with atrial fibrillation (AF) taking warfarin sodium despite a well-established therapeutic range.ObjectiveTo evaluate whether history of therapeutic warfarin control in patients with AF is independently associated with subsequent bleeding or thrombotic events.Design, setting, and participantsIn this multicenter cohort study of 176 primary care, cardiology, and electrophysiology clinics in the United States, data were obtained during 51 830 visits among 10 137 patients with AF in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry; 5545 patients treated with warfarin were included in the bleeding analysis, and 5635 patients were included in the thrombotic event analysis. Patient follow-up was performed from June 29, 2010, to November 30, 2014. Data analysis was performed from August 4, 2016, to February 15, 2019.ExposuresMultiple measures of warfarin control within the preceding 6 months were analyzed: time in therapeutic range of 2.0 to 3.0, most recent international normalized ratio (INR), percentage of time that a patient had interpolated INR values less than 2.0 or greater than 3.0, INR variance, INR range, and percentage of INR values in therapeutic range.Main outcomes and measuresAssociation of INR measures, alone or in combination, with clinical factors and risk for thrombotic events and bleeding during the subsequent 6 months was assessed post hoc using logistic regression models.ResultsA total of 5545 patients (mean [SD] age, 74.5 [9.8] years; 3184 [57.4%] male) with AF were included in the major bleeding analysis and 5635 patients (mean [SD] age, 74.5 [9.8] years; 3236 [57.4%] male) in the thrombotic event analysis. During a median follow-up of 1.5 years (interquartile range, 1.0-2.5 years), there were 339 major bleeds (6.1%) and 51 strokes (0.9%). Multiple metrics of warfarin control were individually associated with subsequent bleeding. After adjustment for clinical bleeding risk, 3 measures-time in therapeutic range (per 1-SD increase ≤55: adjusted odds ratio [aOR], 1.16; 95% CI, 1.02-1.32), variation in INR values (aOR, 1.32; 95% CI, 1.19-1.47), and maximum INR (aOR, 1.20; 95% CI, 1.10-1.31)-remained associated with bleeding risk. Adding INR variance to a clinical risk model slightly increased the C statistic from 0.68 to 0.69 and had a net reclassification improvement index of 0.028 (95% CI, -0.029 to 0.067). No INR measures were associated with subsequent stroke risk.Conclusions and relevanceThree metrics of prior warfarin control were associated with bleeding risk but only marginally more so than traditional clinical factors. This study did not identify any measures of INR control that were significantly associated with stroke risk.

Project description:BackgroundA previous FDA study reported a favorable benefit risk for apixaban compared with warfarin for stroke prevention in older non-valvular atrial fibrillation (NVAF) patients (≥ 65 years). However, it remains unclear whether this favorable benefit risk persists in other populations including younger users. We examined if a similar benefit risk was observed in the Sentinel System and if it varied by age group.ObjectiveTo examine the risk of ischemic stroke, gastrointestinal (GI) bleeding, and intracranial hemorrhage (ICH) in apixaban users compared with warfarin users in Sentinel Distributed Database (SDD).Design and participantsA retrospective new user cohort study was conducted among patients, 21 years and older initiating apixaban and warfarin for NVAF, between December 28, 2012, and June 30, 2018, in the SDD.Main measuresCox proportional hazard regression was used to estimate the hazard ratios (HR) and 95% confidence intervals (95% CI) for each outcome (ischemic stroke, GI bleeding, and ICH) in propensity score matched apixaban users compared with the warfarin users. Subgroup analyses by age (21-64, 65-74, and 75+ years) were conducted.Key resultsAfter matching, 55.3% and 58.4% (n = 55,038) of the apixaban and warfarin users were included in the main analysis. GI bleeding was the most common outcome. The HR (95% CI) for GI bleeding, ICH, and ischemic stroke in apixaban users compared with warfarin users were 0.57 (0.50-0.66), 0.53 (0.40-0.70), and 0.56 (0.45-0.71) respectively. The reduced risk of these outcomes in apixaban compared with warfarin users persisted across age groups.ConclusionIn NVAF patients of all ages initiating either apixaban or warfarin for stroke prevention in the Sentinel System, apixaban was associated with a decreased risk of GI bleeding, ICH, and ischemic stroke compared with warfarin. Among patients less than 65 years of age, apixaban use was associated with a decreased risk of GI bleeding and ischemic stroke.

Project description:Bleeding events are the major obstacle to the widespread use of warfarin for secondary stroke prevention. Previous studies have not examined the use of risk stratification scores to estimate lifetime bleeding risk associated with warfarin treatment in a population-based setting. The purpose of this study is to determine the lifetime risk of bleeding events in ischemic stroke patients with atrial fibrillation (AF) undergoing warfarin treatment in a population-based cohort and to evaluate the use of bleeding risk scores to identify patients at high risk for lifetime bleeding events.The resources of the Rochester Epidemiology Project Medical Linkage System were used to identify acute ischemic stroke patients with AF undergoing warfarin treatment for secondary stroke prevention from 1980 to 1994. Medical information for patients seen at Mayo Clinic and at Olmsted Medical Center was used to retrospectively risk-stratify stroke patients according to bleeding risk scores (including the HAS-BLED and HEMORR2HAGES scores) before warfarin initiation. These scores were reassessed 1 and 5 years later and compared with lifetime bleeding events.One hundred patients (mean age, 79.3 years; 68% women) were studied. Ninety-nine patients were observed until death. Major bleeding events occurred in 41 patients at a median of 19 months after warfarin initiation. Patients with a history of hemorrhage before warfarin treatment were more likely to develop major hemorrhage (15% versus 3%, P = .04). Patients with baseline HAS-BLED scores of 2 or more had a higher lifetime risk of major bleeding events compared with those with scores of 1 or less (53% versus 7%, P < .01), whereas those with HEMORR2HAGES scores of 2 or more had a higher lifetime risk of major bleeding events compared with those with scores of 1 or less (52% versus 16%, P = .03). Patients with an increase in the HAS-BLED and HEMORR2HAGES scores during follow-up had a higher remaining lifetime risk of major bleeding events compared with those with no change.Our findings indicate high lifetime bleeding risk associated with warfarin treatment for patients with ischemic stroke. Risk stratification scores are useful to identify patients at high risk of developing bleeding complications and should be recalculated at regular intervals to evaluate the bleeding risk in anticoagulated patients with ischemic stroke.

Dataset Information

The Association Between Bleeding and the Incidence of Warfarin Discontinuation in Patients with Atrial Fibrillation.

Aim

Methods

Results

Conclusions

Publications

The Association Between Bleeding and the Incidence of Warfarin Discontinuation in Patients with Atrial Fibrillation.

Similar Datasets

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