Cost-Effectiveness of Bridging Anticoagulation Among Patients with Nonvalvular Atrial Fibrillation.
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ABSTRACT: Background
Bridging 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.Objective
To 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.Conclusions
Outpatient 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.
SUBMITTER: Pappas MA
PROVIDER: S-EPMC6445930 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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:Three target-specific oral anticoagulants (TSOACs)-dabigatran, rivaroxaban, and apixaban-have been approved by the FDA to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation; however, no agents are currently approved to reverse the anticoagulant effects of these TSOACs in cases of active bleeding. This review discusses the benefits and risks of these TSOACs from a clinician's perspective, with a focus on the interruption of treatment for either elective or emergent surgery, monitoring, and reversal of anticoagulation. Available coagulation assays are not ideal for monitoring the effects of TSOACs and do not provide reliable quantitative measurement of their anticoagulant effects. When necessary, activated partial thromboplastin time (aPTT) may provide qualitative information on dabigatran, and prothrombin time (PT) may provide qualitative assessment of the presence of the factor Xa inhibitors, rivaroxaban and apixaban. Current recommendations for reversal of TSOACs are based largely on limited and sometimes conflicting data from in vitro or in vivo animal models, and clinical experience with these recommendations is also limited. Methods that have been investigated for effectiveness for reversal of the pharmacodynamic effects of the TSOACs include dialysis, activated charcoal, prothrombin complex concentrate (PCC), and recombinant activated factor VII. It is important to note that even within a class of anticoagulant drugs, compounds respond differently to reversal agents; therefore, recommendations for one agent should not be extrapolated to another, even if they are from the same therapeutic class. New antidotes are being explored, including a mouse monoclonal antibody to dabigatran; andexanet alfa, a potential universal factor Xa inhibitor reversal agent; and a synthetic small molecule (PER977) that may be effective for the reversal of factor Xa inhibitors and direct thrombin inhibitors. Given the short half-lives of TSOACs, watchful waiting, rather than reversal, may be the best approach in some circumstances.
| S-EPMC4264672 | biostudies-literature
Project description:It 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.We 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.In 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).In 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:Background and Purpose- This ARISTOPHANES study (Anticoagulants for Reduction in Stroke: Observational Pooled Analysis on Health Outcomes and Experience of Patients) used multiple data sources to compare stroke/systemic embolism (SE) and major bleeding (MB) among a large number of nonvalvular atrial fibrillation patients on non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin. Methods- A retrospective observational study of nonvalvular atrial fibrillation patients initiating apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, to September 30, 2015, was conducted pooling Centers for Medicare and Medicaid Services Medicare data and 4 US commercial claims databases. After 1:1 NOAC-warfarin and NOAC-NOAC propensity score matching in each database, the resulting patient records were pooled. Cox models were used to evaluate the risk of stroke/SE and MB across matched cohorts. Results- A total of 285?292 patients were included in the 6 matched cohorts: 57?929 apixaban-warfarin, 26?838 dabigatran-warfarin, 83?007 rivaroxaban-warfarin, 27?096 apixaban-dabigatran, 62?619 apixaban-rivaroxaban, and 27?538 dabigatran-rivaroxaban patient pairs. Apixaban (hazard ratio [HR], 0.61; 95% CI, 0.54-0.69), dabigatran (HR, 0.80; 95% CI, 0.68-0.94), and rivaroxaban (HR, 0.75; 95% CI, 0.69-0.82) were associated with lower rates of stroke/SE compared with warfarin. Apixaban (HR, 0.58; 95% CI, 0.54-0.62) and dabigatran (HR, 0.73; 95% CI, 0.66-0.81) had lower rates of MB, and rivaroxaban (HR, 1.07; 95% CI, 1.02-1.13) had a higher rate of MB compared with warfarin. Differences exist in rates of stroke/SE and MB across NOACs. Conclusions- In this largest observational study to date on NOACs and warfarin, the NOACs had lower rates of stroke/SE and variable comparative rates of MB versus warfarin. The findings from this study may help inform the discussion on benefit and risk in the shared decision-making process for stroke prevention between healthcare providers and nonvalvular atrial fibrillation patients. Clinical Trial Registration- URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT03087487.
| S-EPMC6257512 | 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:Dabigatran has been shown to be superior to warfarin for stroke prevention in nonvalvular atrial fibrillation (NVAF) but with higher out-of-pocket costs for patients. Although dabigatran has been shown to be cost effective from a societal perspective, cost implications for individual patients and insurers are not well described. We aimed to assess cost perspectives of each payer (Medicare and patient) in relation to administration, monitoring, and adverse outcomes for dabigatran and warfarin in patients with and without prescription drug coverage. Using a Markov model, we performed a decision analysis comparing 2 treatment strategies (dose-adjusted warfarin and dabigatran 150 mg twice daily) in patients 65 years old with NVAF, CHADS2 scores ≥ 1, and Medicare insurance. Patients have a quality-adjusted life expectancy of 8.998 quality-adjusted life years with warfarin and 9.39 quality-adjusted life years with dabigatran 150 mg twice daily. From Medicare's perspective, the incremental cost-effectiveness ratio comparing dabigatran with warfarin was $35,311 for patients with Part D coverage and cost saving for patients without coverage. From the patient's perspective, the incremental cost-effectiveness ratio comparing dabigatran with warfarin was cost saving for patients with Part D coverage and $63,884 for those without coverage. In patients ≥ 65 years with NVAF and prescription insurance coverage, dabigatran 150 mg twice daily is both cost effective (Medicare's perspective) and cost saving (patient perspective) compared with warfarin, at a willingness-to-pay threshold of $100,000. However, patients without prescription drug coverage have a high out-of-pocket cost burden with dabigatran therapy, leading to a reduction in its cost-effectiveness compared with warfarin therapy. In conclusion, this Markov model suggests that Medicare Part D coverage influences the cost-effectiveness of dabigatran 150 mg daily compared with dose-adjusted warfarin from multiple payer perspectives.
| S-EPMC4780215 | biostudies-literature
Project description:Background/objectivesOral anticoagulation (OAC) is challenging in older patients with nonvalvular atrial fibrillation (NVAF) who are often frail and have cognitive impairment. We examined the characteristics of older NVAF patients associated with higher odds of physical and cognitive impairments. We also examined if these high-risk patients have different OAC prescribing patterns and their satisfaction with treatment because it may impact optimal management of their NVAF.MethodsThe patients in the Systematic Assessment of Geriatric Elements in Atrial Fibrillation (SAGE-AF study cohort 2016-2018) had NVAF, were aged 65 and older, and eligible for the receipt of OAC. Measures included frailty (Fried Frailty scale), cognitive impairment (Montreal Cognitive Assessment Battery), OAC prescribing and type (direct oral anticoagulant [DOAC] or vitamin K antagonist [VKA]), depressive symptoms (Patient Health Questionnaire-9), bleeding, stroke risk, and treatment benefit (Anti-Clot Treatment Scale).ResultsPatients (n = 1,244) were 49% female, aged 76 (standard deviation = 7) years. A total of 14% were frail, and 42% had cognitive impairment. Frailty and cognitive impairment co-occurred in 9%. Odds of having both impairments versus none were higher with depression (odds ratio [OR] = 4.62; 95% confidence interval [CI] = 2.59-8.26), older age (OR = 1.56; 95% CI = 1.29-1.88), lower education (OR = 3.81; 95%CI = 2.13-6.81), race/ethnicity other than non-Hispanic White (OR = 7.94; 95% CI = 4.34-14.55), bleeding risk (OR = 1.43; 95% CI = 1.12-1.81), and stroke risk (OR = 1.35; 95% CI = 1.13-1.62). OAC prescribing was not associated with CI and frailty status. Among patients taking OACs (85%), those with both impairments were more likely to take DOAC than VKA (OR = 1.69; 95% CI = 1.01-2.80). Having both impairments (OR = 1.87; 95% CI = 1.08-3.27) or cognitive impairment (OR = 1.56; 95% CI = 1.09-2.24) was associated with higher odds of reporting lower treatment benefit.ConclusionIn a large cohort of older NVAF patients, half were frail or cognitively impaired, and 9% had both impairments. We highlight the characteristics of patients who may benefit from cognitive and physical function screenings to maximize treatment and enhance prognosis. Finally, the co-occurrence of impairment was associated with low perceived benefit of treatment that may impede optimal management.
| S-EPMC8567309 | biostudies-literature
Project description:AbstractPatients 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 registrationBRIDGE ClinicalTrials.gov, NCT00786474.
| S-EPMC4897904 | biostudies-literature
Project description:BackgroundAnticoagulation decreases a patient's risk of ischemic stroke and increases the risk of hemorrhage. Decision analyses regarding anticoagulation therefore require that different outcomes be weighted in comparison to one another. Most decision analyses to date have weighted intracranial hemorrhage (ICH) as 1.5 times worse than ischemic stroke, but because death and disability have lifelong impact, the expected impact should vary by life expectancy. Therefore, a fixed weighting ratio leads to age-related bias decision analyses of anticoagulation. We aimed to quantify the relative impact of ICH and ischemic stroke and derive a ratio that allows decision analysis without microsimulation.MethodsWe created a microsimulation model to predict QALYs lost due to ICH and ischemic stroke. We then applied a meta-model to predict the ratio of QALYs lost from ICH relative to ischemic stroke.ResultsPreviously-used weighting ratios (1.5) are close to our derived mean weighting ratio (1.60). However, the weighting ratio of QALYs lost from ICH relative to ischemic stroke is sensitive to age and discount rate. Patients at younger ages have higher mean weighting ratios, as do patients with higher discount rates.ConclusionsThe ratio of QALYs lost to ICH relative to ischemic stroke varies with age and discount rate. We present a set of such ratios here for use in decision analyses that do not incorporate full microsimulation models. Use of weighting ratios that vary with age, rather than the current fixed ratios, has the potential to reduce age-based bias in decision-making regarding events with lifelong implications. In this case, use of dynamic ratios may change anticoagulation recommendations for patients with nonvalvular atrial fibrillation at relatively low stroke risk.
| S-EPMC6040745 | biostudies-literature
Project description:For warfarin-treated patients with atrial fibrillation (AF) at low thromboembolic risk, recent studies have shown harm associated with periprocedural bridging using low-molecular-weight heparin. Clinician surveys have indicated a preference toward excessive bridging, especially among noncardiologists; however, little is known about actual practice patterns in these patients. We performed a retrospective evaluation of bridging in the setting of gastrointestinal endoscopy. We identified 938 patients with AF on warfarin who underwent esophagogastroduodenoscopy or colonoscopy between 2012 and 2016 at a tertiary health center. Urgent, inpatient, or advanced endoscopic procedures were excluded. Clinical variables were abstracted using a predefined data dictionary. Values were expressed as means and compared using a t test or a chi-squared test as appropriate. Three hundred seventy-four patients met criteria for analysis. Twenty-five percent of these patients received bridging therapy, including 11% of patients with CHADS2 scores of 0 to 2 without valvular AF or previous venous thromboembolism. Of the clinical variables assessed, CHADS2, CHA2DS2-VASc, and a history of stroke were the strongest predictors of bridging. Cardiologists were also significantly less likely to prescribe bridging than noncardiology providers (18% vs 30%, p = 0.011); this effect was significant when controlling for CHADS2, CHA2DS2-VASc, or stroke history. In conclusion, patients with AF on warfarin receive excessive low-molecular-weight heparin bridging in the setting of endoscopy; the lower rates of bridging observed among cardiologists suggests a need for their increased involvement in this decision making.
| S-EPMC6237079 | biostudies-literature