Perioperative bridging anticoagulation for atrial fibrillation-the first randomised controlled trial.
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ABSTRACT: Abstract
Patients who have atrial fibrillation (AF) have increased thromboembolic risk. This risk is mitigated through use of anticoagulants, traditionally with vitamin K antagonists such as warfarin, and more recently with drugs such as Xa and thrombin inhibitors. Since anticoagulants increase the risk of bleeding, uncertainty exists regarding their use in the perioperative period. The risk of thromboembolism for each patient must be balanced against risk of bleeding; anticoagulation medication may be continued, replaced with a short-acting alternative or withheld entirely. Until recently, evidence on best management relied on expert opinion and observational studies. The recent publication of a randomised, double-blind, placebo-controlled trial (BRIDGE) has added important information to the knowledge base.Trial registration
BRIDGE ClinicalTrials.gov, NCT00786474.
SUBMITTER: Wight JM
PROVIDER: S-EPMC4897904 | biostudies-literature | 2016
REPOSITORIES: biostudies-literature
Publications
Perioperative bridging anticoagulation for atrial fibrillation-the first randomised controlled trial.
Wight James Matthew JM Columb Malachy Oliver MO
Perioperative medicine (London, England) 20160607
<h4>Abstract</h4>Patients who have atrial fibrillation (AF) have increased thromboembolic risk. This risk is mitigated through use of anticoagulants, traditionally with vitamin K antagonists such as warfarin, and more recently with drugs such as Xa and thrombin inhibitors. Since anticoagulants increase the risk of bleeding, uncertainty exists regarding their use in the perioperative period. The risk of thromboembolism for each patient must be balanced against risk of bleeding; anticoagulation me ...[more]
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Project description:BackgroundIt is uncertain whether bridging anticoagulation is necessary for patients with atrial fibrillation who need an interruption in warfarin treatment for an elective operation or other elective invasive procedure. We hypothesized that forgoing bridging anticoagulation would be noninferior to bridging with low-molecular-weight heparin for the prevention of perioperative arterial thromboembolism and would be superior to bridging with respect to major bleeding.MethodsWe performed a randomized, double-blind, placebo-controlled trial in which, after perioperative interruption of warfarin therapy, patients were randomly assigned to receive bridging anticoagulation therapy with low-molecular-weight heparin (100 IU of dalteparin per kilogram of body weight) or matching placebo administered subcutaneously twice daily, from 3 days before the procedure until 24 hours before the procedure and then for 5 to 10 days after the procedure. Warfarin treatment was stopped 5 days before the procedure and was resumed within 24 hours after the procedure. Follow-up of patients continued for 30 days after the procedure. The primary outcomes were arterial thromboembolism (stroke, systemic embolism, or transient ischemic attack) and major bleeding.ResultsIn total, 1884 patients were enrolled, with 950 assigned to receive no bridging therapy and 934 assigned to receive bridging therapy. The incidence of arterial thromboembolism was 0.4% in the no-bridging group and 0.3% in the bridging group (risk difference, 0.1 percentage points; 95% confidence interval [CI], -0.6 to 0.8; P=0.01 for noninferiority). The incidence of major bleeding was 1.3% in the no-bridging group and 3.2% in the bridging group (relative risk, 0.41; 95% CI, 0.20 to 0.78; P=0.005 for superiority).ConclusionsIn patients with atrial fibrillation who had warfarin treatment interrupted for an elective operation or other elective invasive procedure, forgoing bridging anticoagulation was noninferior to perioperative bridging with low-molecular-weight heparin for the prevention of arterial thromboembolism and decreased the risk of major bleeding. (Funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health; BRIDGE ClinicalTrials.gov number, NCT00786474.).
| S-EPMC4931686 | biostudies-literature
Project description:Objective: The study objective was to determine if peri-operative bridging anticoagulation in patients with atrial fibrillation is beneficial or harmful.Design: Systematic review and meta-analysis.Setting: Inpatient or in-hospital setting.Participants: Adults with atrial fibrillation having a CHADS2 score >1 undergoing elective surgical procedure on anticoagulation.Methods: A systemic search of multiple databases (Cochrane, Medline, PubMed) was performed regarding studies conducted on efficacy and safety of perioperative bridging anticoagulation in patients with atrial fibrillation. Studies identified were reviewed by two authors individually before inclusion. The results were then pooled using Review Manager to determine the combined effect. Stroke/systemic embolism was considered as the primary efficacy outcome. Major bleeding was the primary safety outcome.Results: The systematic search revealed 108 potential articles. The full texts of 28 articles were retrieved for assessment of eligibility. After full text review, 25 articles were excluded. Three articles met inclusion criteria. No significant difference in stroke/systemic embolism with bridging anticoagulation was noted (risk ratio, 1.25-95% confidence interval [CI], 0.55-2.85). Bridging was associated with significantly higher risk of major bleeding (risk ratio, 3.29-95% CI, 2.25-4.81).Conclusion: An individualized approach is required when initiating peri-operative bridging anticoagulation. There is certainly a higher risk of bleeding with bridging anticoagulation and no difference in stroke/systemic embolism. However, the results cannot be extrapolated to patients who have valvular atrial fibrillation or CHADS2 score of 5 or greater.
| S-EPMC7987095 | biostudies-literature
Project description:BackgroundBridging anticoagulation is commonly prescribed to patients with atrial fibrillation during initiation and interruption of warfarin. Guidelines recommend bridging patients at high risk of stroke, while a recent randomized trial demonstrated overall harm in a population at comparatively low risk of ischemic stroke. Theory suggests that patients at high risk of stroke and low risk of hemorrhage may benefit from bridging, but data informing patient selection are scant.ObjectiveTo estimate the utility and cost-effectiveness of bridging anticoagulation among patients with nonvalvular atrial fibrillation, stratified by thromboembolic and hemorrhagic risk DESIGN: Cost-effectiveness analysis with lifelong time horizon, from the perspective of a third-party payer MAIN MEASURES: Quality-adjusted life years (QALYs) per bridged patient; US dollars per QALY gained KEY RESULTS: Unselected patients with nonvalvular atrial fibrillation may be harmed by bridging anticoagulation. Hospital admission for bridging is almost never cost-effective, and generally harmful. Among patients carefully selected by both thromboembolic and hemorrhagic risks, outpatient bridging can be beneficial and cost-effective. Results were sensitive to how effectively heparin products reduce stroke risk.ConclusionsOutpatient bridging anticoagulation can be beneficial and cost-effective for a subset of patients with nonvalvular atrial fibrillation during interruption or initiation of warfarin. Admission for bridging should be avoided.
| S-EPMC6445930 | biostudies-literature
Project description:BackgroundStroke prevention in atrial fibrillation (AF), most commonly with warfarin, requires maintenance of a narrow therapeutic target (INR 2.0 to 3.0) and is often poorly controlled in practice. Poor patient-understanding surrounding AF and its treatment may contribute to the patient's willingness to adhere to recommendations.MethodA theory-driven intervention, developed using patient interviews and focus groups, consisting of a one-off group session (1-6 patients) utilising an "expert-patient" focussed DVD, educational booklet, self-monitoring diary and worksheet, was compared in a randomised controlled trial (ISRCTN93952605) against usual care, with patient postal follow-ups at 1, 2, 6, and 12-months. Ninety-seven warfarin-naïve AF patients were randomised to intervention (n=46, mean age (SD) 72.0 (8.2), 67.4% men), or usual care (n=51, mean age (SD) 73.7 (8.1), 62.7% men), stratified by age, sex, and recruitment centre. Primary endpoint was time within therapeutic range (TTR); secondary endpoints included knowledge, quality of life, anxiety/depression, beliefs about medication, and illness perceptions.Main findingsIntervention patients had significantly higher TTR than usual care at 6-months (76.2% vs. 71.3%; p=0.035); at 12-months these differences were not significant (76.0% vs. 70.0%; p=0.44). Knowledge increased significantly across time (F (3, 47) = 6.4; p<0.01), but there were no differences between groups (F (1, 47) = 3.3; p = 0.07). At 6-months, knowledge scores predicted TTR (r=0.245; p=0.04). Patients' scores on subscales representing their perception of the general harm and overuse of medication, as well as the perceived necessity of their AF specific medications predicted TTR at 6- and 12-months.ConclusionsA theory-driven educational intervention significantly improves TTR in AF patients initiating warfarin during the first 6-months. Adverse clinical outcomes may potentially be reduced by improving patients' understanding of the necessity of warfarin and reducing their perception of treatment harm. Improving education provision for AF patients is essential to ensure efficacious and safe treatment. The trial is registered with Current Controlled Trials, ISRCTN93952605, and details are available at www.controlled-trials.com/ISRCTN93952605.
| S-EPMC3767671 | biostudies-literature
Project description:The randomized, controlled BRIDGE trial established a lack of efficacy for use of bridging anticoagulation in warfarin-treated patients who underwent surgical procedures. A large nation-wide insurance claims database was used to perform a retrospective interrupted time series cohort study of adult patients with atrial fibrillation treated with warfarin who underwent surgical procedures. Patients were assessed for the use of low-molecular-weight heparin (LMWH) use as a periprocedural bridging anticoagulant between July 2015 and November 2017. The interrupted time series regression model was used to estimate the reduction in use of bridging LMWH following the publication of the BRIDGE trial in July 2015. The cohort consisted of 9,278 warfarin-treated patients with atrial fibrillation. Use of bridging LMWH declined by an estimated 6.7% (95% confidence interval [CI] 2.1% to 11.3%) to 13.0% following publication of the BRIDGE trial. The decline in bridging LMWH use was numerically larger for patients with a moderate- or high risk of stroke (8.9% decline, 95% CI 0.4% to 17.4%) than for patients at low risk for stroke (6.2% decline, 95% CI 0.7% to 11.5%). Significant predictors of bridging LMWH use include younger age and no co-morbid diabetes. In conclusion, this nation-wide, claims-based study identified a significant reduction in the use of bridging LMWH following the publication of the BRIDGE trial for warfarin-treated patients with AF.
| S-EPMC6825891 | biostudies-literature
Project description:BackgroundBridging anticoagulation is commonly prescribed to patients with atrial fibrillation who are initiating warfarin or require interruption of anticoagulation. Current guidelines recommend bridging for patients at high risk of stroke. Among patients with atrial fibrillation and one or more risk factors for ischemic stroke, the recently published BRIDGE trial found forgoing bridging during interruption to be, on average, noninferior to bridging with respect to ischemic complications, with significantly fewer hemorrhagic complications.ObjectiveWe sought to examine the benefits and harms of bridging anticoagulation across the spectrum of ischemic and hemorrhagic stroke risk and thereby enable more nuanced, risk-stratified decision-making when bridging is considered during initiation or interruption of vitamin K antagonists.DesignA Monte Carlo simulation, using a combination of literature-derived estimates, registry data, and trial data.Main measuresNet clinical benefit, weighting for ischemic strokes, intracranial hemorrhages, and extracranial major hemorrhages.Key resultsThe benefits and harms of bridging anticoagulation vary according to underlying patient risk profiles for both thromboembolic stroke and major intracranial bleeding. Patients at high risk of ischemic stroke and low risk of hemorrhage derive benefit from bridging during initiation or interruption of warfarin therapy. Patients at similarly high or low risk of both outcomes may receive benefit from bridging during initiation and bridging during interruption, but this was sensitive to underlying assumptions. The need for stratification along both axes of risk was robust to a wide range of parameters.ConclusionsBridging anticoagulation may provide benefit to patients at high risk of ischemic stroke and low risk of intracranial hemorrhage who are initiating or interrupting warfarin therapy, while patients at high or low risk of both complications may be harmed. The use of bridging anticoagulation in patients with non-valvular atrial fibrillation should be considered only after stratification by risk of ischemic and hemorrhagic complications.
| S-EPMC5377884 | biostudies-literature
Project description:Patients with atrial fibrillation (AF) are at increased thromboembolic risk, and they suffer more severe strokes with worse outcomes. Most thromboembolic complications of AF are eminently preventable with oral anticoagulation, and the increasing numbers of AF patients mean antithrombotic therapy is the most crucial management aspect of this common arrhythmia. Despite the proven efficacy of warfarin, a string of limitations have meant that it is underused by physicians and patients alike. This has prompted a search for new anticoagulants that could overcome many of the inconveniences of dose variability and anticoagulant monitoring associated with warfarin, but without sacrificing efficacy in thromboprophylaxis. The arrival of new oral anticoagulants has been complemented by improved risk stratification schemes, which permit clinicians to easily and reliably identify patients requiring anticoagulation and their bleeding risk. These advances in AF treatment will hopefully translate into improved outcomes for patients, especially as our experience with the new agents grows.
| S-EPMC4711491 | biostudies-other
Project description:IntroductionSubdural haematomas (SDHs), acute or chronic, are common neurosurgical diagnoses. These problems can occur among patients requiring direct oral anticoagulation (DOAC) for atrial fibrillation. There are currently no guidelines regarding the optimal timing to resume anticoagulation for these patients after SDH. The objective of this study is to evaluate the feasibility of conducting a future large randomised controlled trial (RCT) evaluating the safety and efficacy of resuming DOACs early (ie, at 30 days) vs late (ie, at 3 months) for patients with atrial fibrillation following diagnosis of SDH.Methods and analysisThis is a pilot, open-label, multicentre RCT that will enrol adults with newly diagnosed acute or chronic SDH with or without other intracranial bleeding who were receiving therapeutic anticoagulation with a DOAC as stroke prophylaxis for atrial fibrillation. Patients will be randomly allocated to resume a DOAC at standard dosing starting either days 30+7 or days 90±14. The primary outcomes for the pilot RCT are recruitment rate, protocol adherence and patient compliance with the randomly allocated interventions. Secondary outcomes are patient functional outcomes and safety and effectiveness outcomes, which will comprise key endpoints for the future planned RCT. This pilot RCT will provide important data to inform the feasibility of conducting a future, large RCT of early versus late resumption of DOACs for atrial fibrillation stroke prophylaxis in patients newly diagnosed with SDH. The future RCT will help inform management of a commonly encountered clinical dilemma with high associated morbidity and mortality.Ethics and disseminationThis study has been approved by the research ethics board of record. It will be conducted in accordance with the Declaration of Helsinki, Good Clinical Practice guidelines and regulatory requirements. Informed consent will be obtained from eligible patients or substitute decision-makers. Data from this study will inform the design of future, larger RCTs.Trial registration numberNCT05472766.
| S-EPMC11499767 | biostudies-literature
Project description:BackgroundAtrial fibrillation causes one-fifth of ischaemic strokes, with a high risk of early recurrence. Although long-term anticoagulation is highly effective for stroke prevention in atrial fibrillation, initiation after stroke can be delayed by concerns over intracranial haemorrhage risk. Direct oral anticoagulants offer a significantly lower risk of intracranial haemorrhage than other anticoagulants, potentially allowing earlier anticoagulation and prevention of ischaemic stroke recurrence, but the safety and efficacy of this approach has not been established. This article describes the statistical analysis plan for the OPTIMAS trial as an update to the published protocol. It was written prior to the end of patient follow-up, before database lock and thus while the outcome of the trial is still unknown.AimThe optimal timing of anticoagulation after acute ischaemic stroke with atrial fibrillation (OPTIMAS) trial will investigate whether early treatment with a direct oral anticoagulant within 4 days of stroke onset is as effective as, or better than, delayed initiation at 7 to 14 days from onset.Methods and designOPTIMAS is a multicentre randomised controlled trial with blinded outcome adjudication. Participants with acute ischaemic stroke and atrial fibrillation eligible for anticoagulation with a direct oral anticoagulant are randomised 1:1 to early or delayed initiation. Here, we describe in detail the statistical aspects of OPTIMAS, including outcome measures, sample size calculation, general analysis principles, descriptive statistics, statistical models, and planned subgroup analyses.Study outcomesThe primary outcome is a composite of recurrent stroke (ischaemic stroke or symptomatic intracranial haemorrhage) and systemic arterial embolism within 90 days. Secondary outcomes include each individual component of the composite outcome, major bleeding, functional status assessed by the modified Rankin Scale, ongoing anticoagulation, quality of life, health and social care resource use, and length of hospital stay.DiscussionOPTIMAS aims to provide high-quality evidence on the safety and efficacy of early direct oral anticoagulant initiation after atrial fibrillation-associated acute ischaemic stroke.Trial registrationsISRCTN: 17,896,007; ClinicalTrials.gov: NCT03759938. Registered on November 30 2018.
| S-EPMC11837694 | biostudies-literature
Project description:BackgroundOral anticoagulants reduce the risk of stroke in patients with atrial fibrillation. However, many patients with atrial fibrillation at elevated stroke risk are not treated with oral anticoagulants.ObjectiveTo test whether electronic notifications sent to primary care physicians increase the proportion of ambulatory patients prescribed oral anticoagulants.DesignRandomized controlled trial conducted from February to May 2017 within 18 practices in an academic primary care network.ParticipantsPrimary care physicians (n = 175) and their patients with atrial fibrillation, at elevated stroke risk, and not prescribed oral anticoagulants.InterventionPatients of each physician were randomized to the notification or usual care arm. Physicians received baseline email notifications and up to three reminders with patient information, educational material and primary care guidelines for anticoagulation management, and surveys in the notification arm.Main measuresThe primary outcome was the proportion of patients prescribed oral anticoagulants at 3 months in the notification (n = 972) vs. usual care (n = 1364) arms, compared using logistic regression with clustering by physician. Secondary measures included survey-based physician assessment of reasons why patients were not prescribed oral anticoagulants and how primary care physicians might be influenced by the notification.Key resultsOver 3 months, a small proportion of patients were newly prescribed oral anticoagulants with no significant difference in the notification (3.9%, 95% CI 2.8-5.3%) and usual care (3.2%, 95% CI 2.4-4.2%) arms (p = 0.37). The most common, non-exclusive reasons why patients were not on oral anticoagulants included atrial fibrillation was transient (30%) or paroxysmal (12%), patient/family declined (22%), high bleeding risk (20%), fall risk (19%), and frailty (10%). For 95% of patients, physicians stated they would not change their management after reviewing the alert.ConclusionsElectronic physician notification did not increase anticoagulation in patients with atrial fibrillation at elevated stroke risk. Primary care physicians did not prescribe anticoagulants because they perceived the bleeding risk was too high or stroke risk was too low.Trial registrationClinicalTrials.gov identifier NCT02950285.
| S-EPMC6258628 | biostudies-literature