Effectiveness and safety in non-valvular atrial fibrillation patients switching from warfarin to direct oral anticoagulants in US healthcare claims.

INTRODUCTION: There is a paucity of real-world studies examining the risks of stroke/systemic embolism (SE) and major bleeding (MB) among non-valvular atrial fibrillation (NVAF) patients switching from warfarin to a direct oral anticoagulant (DOAC). This retrospective study was conducted to compare the stroke/SE and MB risks between patients switched from warfarin to apixaban, dabigatran, or rivaroxaban in real-world clinical practice. MATERIALS AND METHODS: This study used data from four United States commercial claims databases from January 1, 2012 to June 30, 2019. The study population included NVAF patients initially treated with warfarin and switched to apixaban, dabigatran, or rivaroxaban within 90 days of their warfarin prescription ending. Patients were matched 1:1 between the DOACs in each database using propensity scores and then pooled for the final analysis. Cox proportional hazards models were used to calculate the risk of stroke/SE and MB. RESULTS AND CONCLUSIONS: The final population consisted of 2,611 apixaban-dabigatran, 12,165 apixaban-rivaroxaban, and 2,672 dabigatran-rivaroxaban pairs. Apixaban vs. dabigatran was associated with a lower risk of stroke/SE (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.39-0.96) and MB (HR: 0.67; 95% CI: 0.50-0.91). Apixaban vs. rivaroxaban was associated with a similar risk of stroke/SE (HR: 0.88; 95% CI: 0.73-1.07) and a lower risk of MB (HR: 0.60; 95% CI: 0.52-0.68). There was no significant difference in either risk between dabigatran and rivaroxaban. These results provide important insights into how the risks of stroke/SE and MB for NVAF patients vary when switching from warfarin to different DOACs.

Effectiveness and safety of oral anticoagulants in non-valvular atrial fibrillation patients with prior bleeding events: a retrospective analysis of administrative claims databases.

INTRODUCTION: There are a paucity of real-world data examining effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in nonvalvular atrial fibrillation (NVAF) patients with prior bleeding. METHODS: This retrospective analysis included data from 5 insurance claims databases and included NVAF patients prescribed OACs with prior bleeding. One-to-one propensity score matching was conducted between NOACs and warfarin and between NOACs in each database. Cox proportional hazards models were used to evaluate the risk of stroke/systemic embolism (SE) and MB. RESULTS: A total of 244,563 patients (mean age 77; 50% female) with prior bleeding included 55,094 (22.5%) treated with apixaban, 12,500 (5.1%) with dabigatran, 38,246 (15.6%) with rivaroxaban, and 138,723 (56.7%) with warfarin. Apixaban (hazard ratio [HR]: 0.76 [95% CI: 0.70, 0.83]) and rivaroxaban (HR: 0.79 [95% CI: 0.71, 0.87]) had a lower risk of stroke/SE vs. warfarin. Apixaban (HR: 0.67 [95% CI: 0.64, 0.70]) and dabigatran (HR: 0.88 [95% CI: 0.81, 0.96]) had a lower risk of MB vs. warfarin. Apixaban patients had a lower risk of stroke/SE vs. dabigatran (HR: 0.70 [95% CI: 0.57, 0.86]) and rivaroxaban (HR: 0.85 [95% CI: 0.76, 0.96]) and a lower risk of MB than dabigatran (HR: 0.73 [95% CI: 0.67, 0.81]) and rivaroxaban (HR: 0.64 [95% CI: 0.61, 0.68]). CONCLUSIONS: In this real-world analysis of a large sample of NVAF patients with prior bleeding, NOACs were associated with similar or lower risk of stroke/SE and MB vs. warfarin and variable risk of stroke/SE and MB against each other.

Thromboembolic prevention and anticoagulant therapy during the COVID-19 pandemic: updated clinical guidance from the anticoagulation forum.

Thromboembolism is a common and deadly consequence of COVID-19 infection for hospitalized patients. Based on clinical evidence pre-dating the COVID-19 pandemic and early observational reports, expert consensus and guidance documents have strongly encouraged the use of prophylactic anticoagulation for patients hospitalized for COVID-19 infection. More recently, multiple clinical trials and larger observational studies have provided evidence for tailoring the approach to thromboprophylaxis for patients with COVID-19. This document provides updated guidance for the use of anticoagulant therapies in patients with COVID-19 from the Anticoagulation Forum, the leading North American organization of anticoagulation providers. We discuss ambulatory, in-hospital, and post-hospital thromboprophylaxis strategies as well as provide guidance for patients with thrombotic conditions who are considering COVID-19 vaccination.

Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: interim clinical guidance from the anticoagulation forum.

Coronavirus disease 2019 (COVID-19) is a viral infection that can, in severe cases, result in cytokine storm, systemic inflammatory response and coagulopathy that is prognostic of poor outcomes. While some, but not all, laboratory findings appear similar to sepsis-associated disseminated intravascular coagulopathy (DIC), COVID-19- induced coagulopathy (CIC) appears to be more prothrombotic than hemorrhagic. It has been postulated that CIC may be an uncontrolled immunothrombotic response to COVID-19, and there is growing evidence of venous and arterial thromboembolic events in these critically ill patients. Clinicians around the globe are challenged with rapidly identifying reasonable diagnostic, monitoring and anticoagulant strategies to safely and effectively manage these patients. Thoughtful use of proven, evidence-based approaches must be carefully balanced with integration of rapidly emerging evidence and growing experience. The goal of this document is to provide guidance from the Anticoagulation Forum, a North American organization of anticoagulation providers, regarding use of anticoagulant therapies in patients with COVID-19. We discuss in-hospital and post-discharge venous thromboembolism (VTE) prevention, treatment of suspected but unconfirmed VTE, laboratory monitoring of COVID-19, associated anticoagulant therapies, and essential elements for optimized transitions of care specific to patients with COVID-19.

Effectiveness and Safety of Oral Anticoagulants Among Nonvalvular Atrial Fibrillation Patients.

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.

A case-based approach to implementing guidelines for stroke prevention in patients with atrial fibrillation: balancing the risks and benefits.

Atrial fibrillation (AF) puts patients at risk of complications, including stroke. Warfarin therapy has been the mainstay of antithrombotic treatment for reducing the risk of stroke in AF. However, warfarin has limitations that have motivated development of several novel oral anticoagulants (NOACs), including dabigatran, rivaroxaban, apixaban, and edoxaban. Clinical trials demonstrate that the NOACs offer efficacy and safety that are equivalent to, or better than, those of warfarin for reducing the risk of stroke in patients with nonvalvular AF. This review examines stroke risk reduction in patients with AF from the perspective of the clinician balancing the risks and benefits of treatment options, evaluates the most recent guidelines, and discusses 2 hypothetical patient cases to better illustrate how clinicians may apply available data in the clinical setting. We reviewed guidelines for the reduction of stroke risk in AF and data from clinical trials on the NOACs. Choosing antithrombotic treatment involves assessing the benefits of therapy versus its risks. Risk indexes, including CHADS2, CHA2DS2-VASc, and HAS-BLED can help determine how to treat patients with AF. Current guidelines suggest using these risk indexes to customize treatment to individual patients. Many current treatment guidelines also incorporate recommendations for the use of NOACs as an alternative to warfarin. As additional data emerge and guidelines are updated, these recommendations will likely evolve. In the interim, clinicians may consider published guidelines and clinical trial results on NOACs. Real-world experience will provide clinicians with additional insight into their treatment decisions.

Clinical Impact of Switching or Continuation of Apixaban or Rivaroxaban among Patients with Non-Valvular Atrial Fibrillation.

BACKGROUND: Real-world evidence on direct oral anticoagulant outcomes among Non-Valvular Atrial Fibrillation (NVAF) patients is limited. We aimed to evaluate stroke/systemic embolism (SE) and major bleeding (MB) risks among NVAF patients continuing or switching to different oral anticoagulants. METHODS: Using Optum's de-identified Clinformatics® Data Mart Database, we identified NVAF patients initiating apixaban or rivaroxaban between 1 January 2013 and 31 December 2021. Patients switching therapies within 30 days before or 90 days after discontinuing their initial DOAC and those who continued initial therapy were included. The index date was the switch date for switchers, while continuers were assigned a hypothetic index date. Switchers and continuers were propensity score matched based on pre-index characteristics. RESULTS: Among 167,868 apixaban and 65,888 rivaroxaban initiators, 2900 apixaban-to-rivaroxaban switchers were matched with 14,500 apixaban continuers, and 2873 rivaroxaban-to-apixaban switchers were matched with 14,365 rivaroxaban continuers. Apixaban-to-rivaroxaban switching was associated with higher stroke/SE risk (HR: 1.99, 95% CI: 1.38-2.88) and MB risk (HR:1.80, 95% CI: 1.46-2.23) than continuing apixaban. Rivaroxaban-to-apixaban switching had similar stroke/SE risk (HR: 0.74, 95% CI: 0.45-1.22) but lower MB risk (HR: 0.49, 95% CI: 0.38-0.65) than continuing rivaroxaban. CONCLUSIONS: These findings may aid physicians and patients in making informed decisions when considering a switch between apixaban and rivaroxaban.

Healthcare utilization differences between an apixaban-based and warfarin-based strategy for acute venous thromboembolism in patients with end-stage kidney disease.

INTRODUCTION: Evidence suggests that an apixaban-based strategy to treat acute venous thromboembolism (VTE) in patients with End-Stage Kidney Disease (ESKD) may be safer than a warfarin-based strategy. Apixaban has an additional advantage of not requiring bridging with heparin which often necessitates long hospitalizations for patients with ESKD. We sought to determine if an apixaban-based strategy is associated with less healthcare utilization than a warfarin-based strategy. MATERIAL AND METHODS: We employed a new-user, active-comparator retrospective cohort study using inverse probability of treatment weights (IPTW) to adjust for confounding demographic and clinical variables. Patients with ESKD newly initiated on either apixaban or warfarin for an acute VTE between 2014 and 2018 in the United States Renal Data System were included. Outcomes were presence of index hospitalization, length of index hospitalization, total hospital days, total hospital days excluding index hospitalization, total emergency department (ED) visits that did not result in hospitalization, and total skilled nursing facility days. RESULTS: At six months, patients who received apixaban were less likely to have an index hospitalization, had a shorter index hospitalization (median of 4.0 vs 8.0 days, p < 0.001), and had fewer total hospital days. The IPTW and index year-adjusted incidence rate ratios of total hospital days at one, three, and six months were 0.83 (95 % confidence intervals (CI) 0.79-0.86), 0.84 (95 % CI 0.81-0.88), and 0.88 (95 % CI 0.83-0.92) for apixaban compared to warfarin. CONCLUSION: Among patients with ESKD and VTE, resource utilization for an apixaban-based strategy appears to be lower than for a warfarin-based strategy.

Payer formulary tier increases of apixaban: how patients respond and potential implications.

OBJECTIVE: To assess potential impacts of formulary tier increases of apixaban-an efficacious oral anticoagulant (OAC) for preventing stroke in patients with atrial fibrillation (AF)-on patients' prescription drug plan (PDP) switching and OAC treatment patterns. METHODS: Nationwide claims data for Medicare beneficiaries with Parts A, B, and D (100% sample) were used to assess apixaban-treated AF patients who faced a formulary tier increase for apixaban in 2017 by their Part D PDP. Patients' out-of-pocket (OOP) costs for apixaban were described, along with PDP switching and OAC treatment patterns. RESULTS: Among 1845 included patients, 97.7% had apixaban on tier 3 of their plan's formulary in 2016 and faced its increase to tier 4 for 2017. Approximately 4% (N = 81) of patients pre-emptively switched to a different PDP for 2017 with almost all switching to plans with apixaban on a lower formulary tier and 85.2% continuing apixaban treatment. Among the 96% (N = 1764) of patients who remained on the same PDP for 2017, over half (57.5%) continued apixaban treatment, despite increased OOP costs ($54 vs. $135 for a 30-day supply in 2016 vs. 2017). Only 12.4% of those who remained on the same plan for 2017 switched to another OAC, while as much as 30.1% discontinued OACs. These discontinuers exhibited higher comorbidity burdens than patients continuing on any OAC. CONCLUSION: The majority of patients continued on apixaban despite higher OOP cost, suggesting patients' reluctance to change treatment for non-medical reasons; however, 30% of patients discontinued OAC treatment after higher apixaban tier placement.

Delaying clinical events among patients with non-valvular atrial fibrillation treated with oral anticoagulants: Insights from the ARISTOPHANES study.

BACKGROUND: Oral anticoagulants (OACs) mitigate stroke and systemic embolism (SE) risk in non-valvular atrial fibrillation (AF) patients but can increase the risk of major bleeding (MB). This study analyzed the gains in event-free time for these outcomes among OAC treatment options represented in the ARISTOPHANES study. METHODS: This sub-analysis consisted of NVAF patients who initiated warfarin, apixaban, dabigatran, or rivaroxaban from 01JAN2013-30SEP2015, with data pooled from Medicare and 4 US commercial claims databases. Propensity score matching was conducted between non-vitamin K antagonist OAC (NOAC) and warfarin cohorts in each database and results were pooled. Laplace regression was used to evaluate the delay in time to stroke/SE and MB events between NOACs and warfarin and between NOACs after the first 12-months of follow-up. RESULTS: The population included 466,991 patients (167,413 warfarin; 108,852 apixaban; 37,724 dabigatran; and 153,002 rivaroxaban). Event-free time gain (95% confidence interval) for apixaban versus warfarin was 101 days (78- 124) for stroke/SE and 116 (103- 130) days for MB. The gain in event-free time for dabigatran versus warfarin was 45 days (3- 87) for stroke/SE and 92 (68- 116) days for MB. The gain in event-free time for rivaroxaban versus warfarin was 63 days (42- 84) for stroke/SE but event-free time decreased by 18 (-31-6) days for MB. CONCLUSIONS: Over 12 months after initiation, apixaban and dabigatran conferred progressive increases in event free time for stroke/SE and MB vs warfarin, whereas rivaroxaban conferred an increase in stroke/SE-free time but a loss in MB-free time vs warfarin.

Journey to anticoagulant access following payer rejection of apixaban.

OBJECTIVES: To investigate the journey to oral anticoagulant (OAC) access following formulary-related rejection of apixaban (Eliquis) and evaluate characteristics associated with failure to achieve OAC access among patients with atrial fibrillation (AF). STUDY DESIGN: Retrospective study using the Optum Market Clarity Data from January 2016 through February 2020. METHODS: Patients had at least 1 claim rejection for apixaban due to prior authorization (PA), formulary exclusion (FE), or quantity limit (QL) and at least 1 AF diagnosis on or before the rejected claim. Descriptive statistics summarized transaction journeys by type of formulary restriction. Multivariable regression assessed patient characteristics associated with not receiving an OAC within 60 days after initial rejection. RESULTS: Among 18,434 patients in the analytic sample, QL was the most common reason for rejection (68.7%), followed by PA (21.2%) and FE (10.2%). Most patients received a paid OAC claim within 60 days after rejection (82.2%-85.5% across restriction types). Mean time from rejection to paid claim ranged from 5.2 to 10.7 days among patients with a paid OAC claim and 12.4 to 17.6 days among those with multiple attempts before OAC receipt. Characteristics associated with higher odds of not receiving OAC treatment included being male, beingAfrican American, having Medicaid coverage, possessing a high stroke risk score, exhibiting no evidence of prior apixaban treatment, and being prescribed a low dose of apixaban on the initial rejected claim. CONCLUSIONS: Most patients with a claim rejection for apixaban received approval for apixaban within 60 days, suggesting that initial rejection merely created a delay in treatment. Vulnerable populations were at greater risk of not receiving a paid OAC claim.

Payer formulary exclusions of apixaban: how patients respond and potential implications.

In recent years, US payers have increased usage of formulary exclusions as a means to help manage costs. Earlier this year, one of the largest pharmacy benefit managers in the country added Eliquis (apixaban), the most widely used anticoagulant, to its list of excluded medicines from its formulary, raising concerns by physicians and patients. In this commentary, we examine the potential impacts of formulary exclusion of a drug like apixaban-a treatment for patients with atrial fibrillation and venous thromboembolism to help prevent stroke and clotting events and which has been demonstrated to have a strong efficacy and safety profile. We discuss the effect of formulary exclusions on patients' ability to access the most clinically appropriate treatment for their health needs, along with possible effects on their health and well-being. We also report descriptive results on apixaban-treated patients with traditional Medicare coverage who faced a formulary exclusion of apixaban in 2017, and these patients' observed behaviors. We found that the majority of these patients remained on apixaban either through pre-emptively switching to a different Part D drug plan with apixaban coverage or applying for formulary exception. Our findings suggest that formulary exclusion did not help to achieve the goal of switching patients to less costly medications but created additional hurdles for patients to access their preferred treatment and increased patient burden. Alternative ways to manage payer costs may be needed to help avoid poor outcomes and reduce the burden placed on patients in their efforts to access life-saving medications.

Safety and effectiveness of apixaban versus warfarin for acute venous thromboembolism in patients with end-stage kidney disease: A national cohort study.

BACKGROUND: Patients with end-stage kidney disease (ESKD) are at significantly increased risk for both thrombosis and bleeding relative to those with normal renal function. The optimal therapy of venous thromboembolism (VTE) in patients with ESKD is unknown. OBJECTIVE: To compare the safety and effectiveness of apixaban relative to warfarin in patients with ESKD and acute VTE. DESIGN, SETTING AND PARTICIPANTS: New-user, active-comparator retrospective United States population-based cohort with inverse probability of treatment weighting, using the United States Renal Data System data from 2014 to 2018. We included adults with ESKD on hemodialysis or peritoneal dialysis who were newly initiated on apixaban or warfarin for an acute VTE. MAIN OUTCOME AND MEASURES: The coprimary outcomes were major bleeding, recurrent VTE, and all-cause mortality within 6 months of anticoagulant initiation. Secondary outcomes were intracranial hemorrhage and gastrointestinal bleeding. The primary analyses were based on intent-to-treat defined by the first drug received and accounted for competing risks of death. Sensitivity analyses included varied follow-up time, as-treated analyses, and dose-specific apixaban subgroups. RESULTS: The apixaban and warfarin cohorts included 2302 and 9263 patients, respectively. Apixaban was associated with a lower risk of major bleeding (hazard ratio [HR] 0.81, 95% confidence interval [CI]: 0.70-0.94), intracranial bleeding (HR 0.69, 95% CI 0.48-0.98), and gastrointestinal bleeding (HR 0.82, 95% CI 0.69-0.96). Recurrent VTE and all-cause mortality were not significantly different between the groups. CONCLUSION: Apixaban was associated with a lower risk of bleeding relative to warfarin when used to treat acute VTE in patients with ESKD on dialysis.

Impact of apixaban treatment discontinuation on the risk of hospitalization among patients with nonvalvular atrial fibrillation and COVID-19.

INTRODUCTION: This study evaluated the risk of hospitalization among nonvalvular atrial fibrillation (NVAF) patients with an outpatient COVID-19 diagnosis who discontinued vs continued apixaban treatment. METHODS: Adult patients with NVAF with an apixaban prescription prior to an outpatient COVID-19 diagnosis were identified from Optum Clinformatics claims database (1 April 2020-31 March 2021). Continuers were those who continued apixaban as of the index date (date of initial outpatient COVID-19 diagnosis) and discontinuers were those who had the last day of apixaban supply on or before index. Patients were followed from COVID-19 diagnosis to change of continuation/discontinuation status, switch, death, end of continuous coverage or study end, whichever occurred first. Inverse probability treatment weighting (IPTW) was performed to balance cohorts. Cox proportional hazard models were used to compare the risk of all-cause hospitalization and hospitalization for ischemic stroke (IS), venous thromboembolism (VTE), myocardial infarction (MI), bleeding and mortality. RESULTS: A total of 7869 apixaban patients with COVID-19 were included: 6676 continuers (84.8%) and 1193 discontinuers (15.2%). Compared with continuers, discontinuers had a higher risk of all-cause hospitalization (hazard ratio [HR]: 1.23; 95% confidence interval [CI]: 1.08-1.40), IS (HR: 2.00; 95% CI: 1.03-3.87), VTE (HR: 2.37; 95% CI: 1.06-5.27) and mortality (HR: 2.28; 95% CI: 1.85-2.80). There were no significant differences in the risk of MI (HR: 1.01; 95% CI: 0.54-1.90) or bleeding-related hospitalization (HR: 1.13; 95% CI: 0.73-1.76). CONCLUSION: NVAF patients with COVID-19 who discontinued apixaban had a higher risk of hospitalization and thrombotic events vs those who continued apixaban, with no significant difference in bleeding-related hospitalization.

Real-world evidence comparing oral anticoagulants in non-valvular atrial fibrillation: a systematic review and network meta-analysis.

Aim: To compare real-world effectiveness/safety of non-vitamin K antagonist oral anticoagulants and vitamin K antagonists among patients with non-valvular atrial fibrillation. Materials & methods: A systematic review of electronic databases yielded 7661 citations published from January 2013 to January 2020. Fifty-five studies were included in Bayesian network meta-analyses of hazard ratios. Results & conclusion: In comparison with vitamin K antagonists, apixaban, dabigatran and rivaroxaban were associated with a reduced risk of stroke or systemic embolism, ischemic stroke, intracranial hemorrhage and all-cause mortality. Apixaban, dabigatran and edoxaban, but not rivaroxaban, were associated with a reduced risk of major bleeding. This study confirmed the effectiveness and safety of non-vitamin K antagonist oral anticoagulants for the treatment of non-valvular atrial fibrillation in real-world settings, consistent with clinical trial evidence.

This study aimed to compare real-world effectiveness/safety of non-vitamin K antagonist oral anticoagulants and vitamin K antagonists among patients with non-valvular atrial fibrillation. A systematic review was conducted from January 2013 to January 2020, and a total of 7661 references were assessed for relevance. Fifty-five studies were combined in the analysis; in comparison with vitamin K antagonists, apixaban, dabigatran and rivaroxaban were associated with a reduced risk of stroke or systemic embolism, ischemic stroke, intracranial hemorrhage and all-cause mortality. Apixaban, dabigatran and edoxaban, but not rivaroxaban, were associated with a reduced risk of major bleeding. This study confirmed the effectiveness and safety of non-vitamin K antagonist oral anticoagulants for the treatment of non-valvular atrial fibrillation in real-world settings, consistent with clinical trial evidence.

Risk Levels and Adverse Clinical Outcomes Among Patients With Nonvalvular Atrial Fibrillation Receiving Oral Anticoagulants.

Importance: The CHA2DS2-VASc score (calculated as congestive heart failure, hypertension, age 75 years and older, diabetes, stroke or TIA, vascular disease, age 65 to 74 years, and sex category) is the standard for assessing risk of stroke and systemic embolism and includes age and thromboembolic history. To our knowledge, no studies have comprehensively evaluated safety and effectiveness outcomes among patients with nonvalvular atrial fibrillation receiving oral anticoagulants according to independent, categorical risk strata. Objective: To evaluate the incidence of key adverse outcomes among patients with nonvalvular atrial fibrillation receiving oral anticoagulants by CHA2DS2-VASc risk score range, thromboembolic event history, and age group. Design, Setting, and Participants: This cohort study was a retrospective claims data analysis using combined data sets from 5 large health claims databases. Eligible participants were adult patients with nonvalvular atrial fibrillation who initiated oral anticoagulants. Data were analyzed between January 2012 and June 2019. Exposure: Initiation of oral anticoagulants. Main Outcomes and Measures: We observed clinical outcomes (including stroke or systemic embolism, major bleeding, and a composite outcome) on treatment through study end, censoring for discontinuation of oral anticoagulants, death, and insurance disenrollment. The population was stratified by CHA2DS2-VASc risk score; history of stroke, systemic embolism, or transient ischemic attack; and age groups. We calculated time to event, incidence rates, and cumulative incidence for outcomes. Results: We identified 1 141 097 patients with nonvalvular atrial fibrillation; the mean (SD) age was 75.0 (10.5) years, 608 127 patients (53.3%) were men, and over 1 million were placed in the 2 highest risk categories (high risk 1, 327 766 participants; high risk 2, 688 449 participants). Deyo-Charlson Comorbidity Index scores ranged progressively alongside CHA2DS2-VASc risk score strata (mean [SD] scores: low risk, 0.4 [1.0]; high risk 2, 4.1 [2.9]). The crude incidence of stroke and systemic embolism generally progressed alongside risk score strata (low risk, 0.25 events per 100 person-years [95% CI, 0.18-0.34 events]; high risk 2, 3.43 events per 100 person-years [95% CI, 3.06-4.20 events]); patients at the second-highest risk strata with thromboembolic event history had higher stroke incidence vs patients at the highest risk score strata without event history (2.06 events per 100 person-years [95% CI, 2.00-3.12 events] vs 1.18 events per 100 person-years [95% CI, 1.14-1.30 events]). Major bleeding and composite incidence also increased progressively alongside risk score strata (major bleeding: low risk, 0.68 events per 100 person-years [95% CI, 0.56-0.82 events]; high risk 2, 6.29 events per 100 person-years [95% CI, 6.21-6.62 events]; composite incidence: 1.22 events per 100 person-years [95% CI, 1.06-1.41 events]; high risk 2, 10.67 events per 100 person-years [95% CI, 10.26-11.48 events]). The 12-month cumulative incidence proportions for stroke and systemic embolism, major bleeding, and composite outcomes progressed alongside risk score strata (stroke or systemic embolism, 0.30%-1.85%; major bleeding, 0.55%-5.55%; composite, 1.05%-8.23%). Age subgroup analysis followed similar trends. Conclusions and Relevance: The observed incidence of stroke or systemic embolism and major bleeding events generally conformed to an expected increasing incidence by risk score, adding insight into the importance of specific risk score range, thromboembolic event history, and age group strata. These results can help inform clinical decision-making, research, and policy.

Venous thromboembolism in the US: does race matter?

Studies investigating racial differences in the prevalence of venous thromboembolism (VTE) have generally been conducted on a limited scale. This analysis measured VTE prevalence across racial groups in a population of US Medicaid enrollees from 2002 to 2005. Records for patients aged ≥ 18 years with VTE between January 1, 2002 and December 31, 2005 were retrieved from the MarketScan® Multi-State Medicaid Database from Thomson Reuters. Patients were classified as having VTE in each calendar year by the presence of a VTE diagnosis on an inpatient claim or ≥ 1 outpatient claim with VTE diagnosis plus evidence of anticoagulant use. Patients dually eligible for Medicaid and Medicare were excluded. Logistic regression was used to calculate the odds of VTE. An average of 4.5 million Medicaid enrollees were study eligible in each calendar year, 72.2% of which had deep-vein thrombosis, 22.5% pulmonary embolism, and 5.3% had both. Patients were mainly Caucasian (46.8%), African-American (26.0%), and Hispanic (14.1%). VTE prevalence per 100,000 enrollees was highest in African-American males (584 in 2002-784 in 2005), followed by Caucasian males (457-643), Caucasian females (335-446), and African-American females (348-444). Hispanic males (94-149) and females (93-154) had lower prevalence of VTE. African-Americans had a significantly higher probability of having a VTE event than Caucasians (adjusted odds ratio 1.04, 95% confidence interval 1.00-1.07, P = 0.036). VTE prevalence increased over the study period and was highest in African-American males. More coordinated efforts are required to improve VTE awareness and prevention across all racial and ethnic groups.

Real-world persistence to direct oral anticoagulants in patients with atrial fibrillation: a systematic review and network meta-analysis.

OBJECTIVE: To conduct a systematic review and network meta-analysis of real-world evidence comparing adherence, persistence, cost, and utilization between oral anticoagulant (OAC) in non-valvular atrial fibrillation (NVAF) patients. METHODS: A systematic search of MEDLINE and Embase (inception-July 2019) was conducted for published observational cohort studies comparing outcomes between ≥2 OACs. A network meta-analysis was performed to estimate odds ratios for non-persistence using a random-effects model. RESULTS: There were 80 studies evaluating the outcomes of interest. However, due to a paucity in adherence studies and heterogeneity in adherence, cost, and utilization definitions, persistence was the focus of this network meta-analysis. There were 36 studies evaluating non-persistence in 395,593 participants, 24 of which used 3 gap definitions (30-, 60-, and 90-days); 18 unique studies evaluating non-persistence at 12 months were included in the network meta-analysis. Using 30- and 90-day gaps, all NOACs, when compared with VKAs, had lower odds of non-persistence (30-day OR (95%CI): apixaban: 0.63 (0.58, 0.69); rivaroxaban: 0.69 (0.62, 0.76); dabigatran: 0.89 (0.82, 0.97); 90-day OR (95%CI): apixaban: 0.33 (0.22, 0.47); rivaroxaban: 0.47 (0.36, 0.61); dabigatran 0.61 (0.44, 0.85)). When using a 60-day gap, dabigatran had higher odds of non-persistence vs VKAs (OR: 1.35; 95%CI: 1.12, 1.61), but there were no significant differences for apixaban and rivaroxaban. Apixaban had the lowest probability of non-persistence across the 3-gap definitions (95.7% with 30-day gap, 76.9% with 60-day gap, 98.4% with 90-day gap). CONCLUSIONS: The current findings, despite multiple limitations, can raise awareness and understanding of real-world persistence associated with OAC therapy in NVAF patients.

Effectiveness and Safety of Oral Anticoagulants Among Nonvalvular Atrial Fibrillation Patients With Active Cancer.

BACKGROUND: Patients with cancer are more likely to develop nonvalvular atrial fibrillation (NVAF). Currently there are no definitive clinical trials or treatment guidelines for NVAF patients with concurrent cancer. OBJECTIVES: This subgroup analysis of the ARISTOPHANES study compared the risk of stroke/systemic embolism (stroke/SE) and major bleeding (MB) among NVAF patients with active cancer who were prescribed non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin. METHODS: A retrospective observational study was conducted in NVAF patients with active cancer who newly initiated apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, through September 30, 2015, with the use of Medicare and 4 U.S. commercial claims databases. Cox models were used to estimate the risk of stroke/SE and MB in the pooled propensity score-matched cohorts. RESULTS: A total of 40,271 patients were included, with main cancer types of prostate (29%), female breast (17%), genitourinary (14%), and lung (13%). Compared with warfarin, apixaban was associated with a lower risk of stroke/SE (hazard ratio [HR]: 0.59; 95% confidence interval [CI]: 0.45-0.78) and MB (HR: 0.58; 95% CI: 0.50-0.68); dabigatran and rivaroxaban had similar risks of stroke/SE (dabigatran: HR: 0.88 [95% CI: 0.54-1.41]; rivaroxaban: HR: 0.82 [95% CI: 0.62-1.08]) and MB (dabigatran: HR: 0.76 [95% CI: 0.57-1.01]; rivaroxaban: HR: 0.95 [95% CI: 0.85-1.06]). Risks of stroke/SE and MB varied among NOAC-NOAC comparisons, while consistent treatment effects were seen for all treatment comparisons across key cancer types. CONCLUSIONS: Among this cohort of NVAF patients with active cancer, the risk of stroke/SE and MB varied among oral anticoagulants and were consistent across cancer types.

Burden of major gastrointestinal bleeding among oral anticoagulant-treated non-valvular atrial fibrillation patients.

BACKGROUND: Gastrointestinal (GI) bleeding is the most common type of major bleeding associated with oral anticoagulant (OAC) treatment. Patients with major bleeding are at an increased risk of a stroke if an OAC is not reinitiated. METHODS: Non-valvular atrial fibrillation (NVAF) patients initiating OACs were identified from the Centers for Medicare and Medicaid Services (CMS) Medicare data and four US commercial claims databases. Patients who had a major GI bleeding event (hospitalization with primary diagnosis of GI bleeding) while on an OAC were selected. A control cohort of patients without a major GI bleed during OAC treatment was matched to major GI bleeding patients using propensity scores. Stroke/systemic embolism (SE), major bleeding, and mortality (in the CMS population) were examined using Cox proportional hazards models with robust sandwich estimates. RESULTS: A total of 15,888 patients with major GI bleeding and 833,052 patients without major GI bleeding were included in the study. Within 90 days of the major GI bleed, 58% of patients discontinued the initial OAC treatment. Patients with a major GI bleed had a higher risk of stroke/SE [hazard ratio (HR): 1.57, 95% confidence interval (CI): 1.42-1.74], major bleeding (HR: 2.79, 95% CI: 2.64-2.95), and all-cause mortality (HR: 1.29, 95% CI: 1.23-1.36) than patients without a major GI bleed. CONCLUSION: Patients with a major GI bleed on OAC had a high rate of OAC discontinuation and significantly higher risk of stroke/SE, major bleeding, and mortality after hospital discharge than those without. Effective management strategies are needed for patients with risk factors for major GI bleeding.