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Trends in warfarin use and its associations with thromboembolic and bleeding rates in a population with atrial fibrillation between 1996 and 2011.

ABSTRACT: Warfarin is a cornerstone for the prevention of thromboembolism in atrial fibrillation (AF), and several efforts have been taken to increase its usage and safety, including risk stratification schemes. Our aim was to investigate the temporal trends in initiation of warfarin and its effects on incidence of bleeding and thromboembolism in patients with new-onset atrial fibrillation 1996-2011.All patients with a first-time diagnosis of non-valvular atrial fibrillation were identified from nationwide administrative registries. Trends were determined by linear regression.In total 153,682 patients were included. Initiation of warfarin increased from 14% to 41% (p<0.0001). Events of thromboembolism decreased from 3.9% to 2.6% annually (p<0.0001). The greatest decline in thromboembolic events was observed for patients with a CHA2DS2VASc score >1, where the annual decline was -0.12% (95%CI: -0.161; -0.084)) for those treated with warfarin and -0.073% (95%CI: -0.116;-0.030)) for those not treated with warfarin. Bleeding increased from 3.3% to 3.9% (p = 0.043). For those with a CHA2DS2VASc score >1 annual bleeding rates increased by 0.095% (95%CI: -0.025; -0.165) in warfarin treated and by 0.056% (95%CI: -0.013; -0.100) in patients not treated with warfarin.Warfarin use increased by nearly a 3-fold between 1996 and 2011. During the same period, thromboembolic events declined by a third and bleeding increased by a fifth, suggesting a beneficial effect associated with higher warfarin use. Notably, a small decline in thromboembolic events and increase in bleeding events was observed for the untreated population, suggesting a changing risk profile of AF patients.

SUBMITTER: Hansen PW

PROVIDER: S-EPMC5856343 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Trends in warfarin use and its associations with thromboembolic and bleeding rates in a population with atrial fibrillation between 1996 and 2011.

Hansen Peter Wæde PW Sehested Thomas S G TSG Fosbøl Emil Loldrup EL Torp-Pedersen Christian C Køber Lars L Andersson Charlotte C Gislason Gunnar H GH

PloS one 20180316 3

<h4>Aim</h4>Warfarin is a cornerstone for the prevention of thromboembolism in atrial fibrillation (AF), and several efforts have been taken to increase its usage and safety, including risk stratification schemes. Our aim was to investigate the temporal trends in initiation of warfarin and its effects on incidence of bleeding and thromboembolism in patients with new-onset atrial fibrillation 1996-2011.<h4>Methods</h4>All patients with a first-time diagnosis of non-valvular atrial fibrillation we ...[more]

PMID: 29547673

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Project description:Objectives To compare stratified event rates from randomized controlled trials with predicted event rates from models developed in observational data, and assess their ability to accurately capture observed rates of thromboembolism and major bleeding for patients treated with dabigatran or warfarin as part of routine care.Design New initiator cohort study.Setting Data from United Health (October 2009 to June 2013), a commercial healthcare claims database in the United States.Participants 21 934 adults with atrial fibrillation initiating dabigatran (150 mg dose only) or warfarin treatment as part of routine care.Main outcome measures Predicted annual rates of thromboembolism or major bleeding, based on estimates from randomized controlled trials, models developed in routine care patients, and baseline risk scores (CHADS2, CHA2DS2-VASc, and HAS-BLED). Thromboembolism was a composite outcome, including primary inpatient diagnosis codes for ischemic or ill defined stroke, transient ischemic attack, pulmonary embolism, deep vein thrombosis, and systemic embolism. Major bleeding was a composite outcome including codes occurring in an inpatient setting for hemorrhagic stroke; major upper, lower, or unspecified gastrointestinal bleed; and major urogenital or other bleed.Results 6516 (30%) and 15 418 (70%) of patients initiated dabigatran and warfarin, respectively. Annual event rates per 100 patients were 1.7 for thromboembolism and 4.6 for major bleeding. For thromboembolism, calibration of estimates from randomized controlled trials was similar to calibration for model based predictions; however, trial estimates for major bleeding consistently underestimated the rate of bleeding among patients in routine care. Underestimation of bleeding rates was particularly pronounced in warfarin initiators with high HAS-BLED scores, where event rates were underestimated by up to 4.0 per 100 patient years. Harrell's c indices for discrimination for thromboembolism or major bleeding in dabigatran and warfarin initiators ranged between 0.59 and 0.66 for randomized controlled trial predictions, and between 0.52 and 0.70 for cross validated model based predictions.Conclusion Estimated rates of thromboembolism under dabigatran or warfarin treatment in randomized controlled trials were close to observed rates in routine care patients. However, rates of major bleeding were underestimated. Models developed in routine care patients can provide accurate, tailored estimates of risk and benefit under alternative treatment to enhance patient centered care.

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:Much of the clinical epidemiology and treatment patterns for patients with atrial fibrillation (AF) are derived from Western populations. Limited data are available on antithrombotic therapy use over time and its impact on the stroke or bleeding events in newly diagnosed Chinese patients with AF. The present study investigates time trends in warfarin and aspirin use in China in relation to stroke and bleeding events in a Chinese population.We used a medical insurance database involving > 10 million individuals for the years 2001 to 2012 in Yunnan, a southwestern province of China, and performed time-trend analysis on those with newly diagnosed AF. Cox proportional hazards time-varying exposures were used to determine the risk of stroke or bleeding events associated with antithrombotic therapy among patients with AF.Among the randomly sampled 471,446 participants, there were 1,237 patients with AF, including 921 newly diagnosed with AF, thus providing 4,859 person-years of experience (62% men; mean attained age, 70 years). The overall rate of antithrombotic therapy was 37.7% (347 of 921 patients), with 4.1% (38 of 921) on warfarin and 32.3% (298 of 921) on aspirin. Antithrombotic therapy was not related to stroke/bleeding risk scores (CHADS2 [congestive heart failure, hypertension, age ? 75 years, diabetes, stroke (doubled)] score, P = .522; CHA2DS2-VASc [congestive heart failure, hypertension, age ? 75 years (doubled), diabetes mellitus, stroke or transient ischemic attack (doubled), vascular disease, age 65 to 74 years, and female sex] score, P = .957; HAS-BLED [hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly (> 65 years), drugs/alcohol concomitantly] score, P = .095). The use of antithrombotic drugs (mainly aspirin) increased in both women and men over time, with the rate of aspirin increasing from 4.0% in 2007 to 46.1% in 2012 in the former, and from 7.7% in 2007 to 61.9% in 2012 in the latter (P for trend for both, < .005). In the overall cohort, the annual stroke rate was approximately 6% and the annual major bleeding rate was about 1%. Compared with nonantithrombotic therapy, the hazard ratio for ischemic stroke was 0.68 (95% CI, 0.39-1.18) for aspirin and 1.39 (0.54-3.59) for warfarin.Aspirin use increased among Chinese patients newly diagnosed with AF, with no relationship to the patient's stroke or bleeding risk. Warfarin use was very low. Given the health-care burden of AF and its complications, our study has major implications for health-care systems in non-Western countries, given the global burden of this common arrhythmia.

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:ObjectivesWe identified factors associated with thromboembolic and bleeding events in two contemporary cohorts of anticoagulated patients with atrial fibrillation (AF), treated with either vitamin K antagonists (VKA) or non-VKA oral anticoagulants (NOACs).DesignProspective, multicentre observational study.Setting461 centres in seven European countries.Participants5310 patients receiving a VKA (PREvention oF thromboembolic events - European Registry in Atrial Fibrillation (PREFER in AF), derivation cohort) and 3156 patients receiving a NOAC (PREFER in AF Prolongation, validation cohort) for stroke prevention in AF.Outcome measuresRisk factors for thromboembolic events (ischaemic stroke, systemic embolism) and major bleeding (gastrointestinal bleeding, intracerebral haemorrhage and other life-threatening bleeding).ResultsThe mean age of patients enrolled in the PREFER in AF registry was 72±10 years, 40% were female and the mean CHA2DS2-VASc Score was 3.5±1.7. The incidence of thromboembolic and major bleeding events was 2.34% (95% CI 1.93% to 2.74%) and 2.84% (95% CI 2.41% to 3.33%) after 1-year of follow-up, respectively.Abnormal liver function, prior stroke or transient ischaemic attack, labile international normalised ratio (INR), concomitant therapy with antiplatelet or non-steroidal anti-inflammatory drugs, heart failure and older age (≥75 years) were independently associated with both thromboembolic and major bleeding events.With the exception of unstable INR values, these risk factors were validated in patients treated with NOACs (PREFER in AF Prolongation Study, 72±9 years, 40% female, CHA2DS2-VASc 3.3±1.6). For each single point decrease on a modifiable bleeding risk scale we observed a 30% lower risk for major bleeding events (OR 0.70, 95% CI 0.64 to 0.76, p<0.01) and a 28% lower rate of thromboembolic events (OR 0.72, 95% CI 0.66 to 0.82, p<0.01).ConclusionAttending to modifiable risk factors is an important treatment target in anticoagulated AF patients to reduce thromboembolic and bleeding events. Initiation of anticoagulation in those at risk of stroke should not be prevented by elevated bleeding risk scores.

Project description:ImportanceTraumatic 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.ObjectiveTo describe the incidence of and risk factors for traumatic intracranial bleeding in a large cohort of older adults who were newly prescribed warfarin sodium.Design, setting, and participantsRetrospective 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.Main outcomes and measuresThe 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.ResultsThe 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.Conclusions and relevanceAmong 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.

Dataset Information

Trends in warfarin use and its associations with thromboembolic and bleeding rates in a population with atrial fibrillation between 1996 and 2011.

Publications

Trends in warfarin use and its associations with thromboembolic and bleeding rates in a population with atrial fibrillation between 1996 and 2011.

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