CV4 EVALUATION OF SURVIVAL AND ISCHAEMIC AND THROMBOEMBOLIC EVENT RATES IN PATIENTS WITH NONVALVULAR ATRIAL FIBRILLATION IN THE GENERAL POPULATION WHEN TREATED AND UNTREATED WITH WARFARIN

Introduction: The randomized ARISTOTLE and RE-LY clinical trials demonstrated that the new oral anticoagulants (NOACs) apixaban and dabigatran were effective and safe options for stroke prevention among non-valvular atrial fibrillation (AF) patients. It is unclear how the use of NOACs for the treatment of AF affects total medical costs. Hypothesis: This study evaluates the hypothesis that medical costs associated with the use of apixaban and dabigatran vs. warfarin are different among the general and elderly AF populations. Methods: Clinical event rates in patients receiving warfarin, apixaban, and dabigatran were estimated for the general and elderly (age ≥ 75 years) AF patient populations. Event rates associated with warfarin were calculated as weighted averages from NOAC trials among AF patients; NOAC rates were estimated by adjusting trial hazard ratios to these weighted averages. Annual incremental costs among patients with clinical events from the US payer perspective were obtained from published literature and inflation adjusted to 2010 cost levels. Medical cost avoidance was evaluated for each NOAC vs. warfarin. Results: Compared to warfarin, apixaban-mediated total medical cost reductions (Table) in both populations were driven by decreased major bleeding excluding hemorrhagic stroke (MBEHS) and stroke and systemic embolism (SSE). Dabigatran use reduced costs for the general population and increased costs for the elderly population; cost reduction in the general population was primarily due to reduced SSE while cost increase in the elderly population was primarily due to increased MBEHS. MI, PE or DVT, and non-major bleeding each made smaller contributions to the cost differences among both populations. Conclusions: Compared to warfarin, apixaban use may be associated with reduced medical costs in both general and elderly AF populations. Dabigatran use may be associated with a reduction of medical costs in the general AF population, but increased medical costs among the elderly.

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Association Between Age and Bleeding Events of Different Severities Among Patients with Nonvalvular Atrial Fibrillation in a Managed Care Population

Blood ◽

10.1182/blood.v120.21.4238.4238 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4238-4238

Author(s):

Steven Deitelzweig ◽

Brett Pinsky ◽

Erin Buysman ◽

Michael Lacey ◽

Yonghua Jing ◽

...

Keyword(s):

Atrial Fibrillation ◽

Emergency Department ◽

Older Patients ◽

Claims Data ◽

Bleeding Events ◽

Nonvalvular Atrial Fibrillation ◽

Employment Equity ◽

Equity Ownership ◽

Event Rates

Abstract Abstract 4238 Background: Risk of bleeding is an important consideration among patients with nonvalvular atrial fibrillation (NVAF) due to the need for stroke prevention through anticoagulation. Older patients may be at risk for more frequent or more severe bleeding events. Objective: To describe the incidence of bleeding events in various age groups of patients with NVAF. Methods: Administrative claims data were used for this retrospective study. Adults with healthcare claims data related to atrial fibrillation (ICD-9-CM 427.31) between Jan 2005 and Jun 2009 but no evidence of valvular disease were included. Patients were followed until the earliest of death, disenrollment from the health plan, or 30 Jun 2010. Bleeding events in the follow-up period were categorized as major, serious non-major, or minor. A bleeding event was considered major if it was associated with any of the following: inpatient care, blood transfusion, decreased hemoglobin or hematocrit, physician guided medical or surgical treatment, intracranial bleed, or death. Serious non-major events were those involving vascular injury or critical site bleeding and were associated with outpatient hospital care or an emergency department visit. Minor bleeds were those associated with noncritical anatomical sites and an emergency department, outpatient hospital, or office visit. Patients were grouped based on their age as of the first atrial fibrillation diagnosis: younger than 65 years or 65 years and older; bleeding events in the subgroup of patients aged 75 years and older were also examined. Results: The mean (SD) age of the study sample (N=48,260) was 67 (13) years and 62.2% of the patients were male. Mean (SD) follow-up duration was 802 (540) days (median 673 days). Event rates for major bleeds were 5.2 events per 100 patient-years for patients aged younger than 65 years and 13.9 major bleeds per 100 patient-years for patients aged 65 years and older. Patients aged 75 and older had 15.6 major bleeds per 100 patient-years. Approximately 38.9% of all bleeding events experienced by patients aged 65 years and older were major. Approximately 23.3%, 33.6%, and 35.8% of major bleeds among patients younger than 65 years, 65 years and older, and 75 years and older, respectively, were associated with a hospitalization. Corresponding event rates for incident bleeds associated with an inpatient stay were 4.7 bleeding events per 100 patient-years for patients aged younger than 65 years, 12.0 events per 100 patient-years for patients aged 65 years and older, and 13.6 events per 100 patient-years for patients aged 75 years and older. Conclusions: Increasing age was associated with increased rate of any type of bleeding. The increase in rate with increasing age was particularly notable for major bleeds. Disclosures: Deitelzweig: Bristol-Myers Squibb/OptumInsight: Research Funding, Speakers Bureau. Pinsky:OptumInsight: Employment. Buysman:OptumInsight: Employment. Lacey:OptumInsight: Employment. Jing:Bristol-Myers Squibb: Employment, Equity Ownership. Wiederkehr:Pfizer: Employment, Equity Ownership. Graham:Bristol-Myers Squibb: Employment, Equity Ownership.

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Comparison of Medical Costs Avoided When New Oral Anticoagulants Are Used for the Treatment of Patients with Atrial Fibrillation and Venous Thromboembolism in the U.S

Blood ◽

10.1182/blood.v124.21.2181.2181 ◽

2014 ◽

Vol 124 (21) ◽

pp. 2181-2181

Author(s):

Alpesh N Amin ◽

Amanda Bruno ◽

Jeffrey Trocio ◽

Jay Lin ◽

Melissa Lingohr-Smith

Keyword(s):

Atrial Fibrillation ◽

Clinical Trials ◽

Venous Thromboembolism ◽

Medical Cost ◽

Oral Anticoagulants ◽

Medical Costs ◽

Nonvalvular Atrial Fibrillation ◽

Equity Ownership ◽

Acute Venous Thromboembolism ◽

Event Rates

Abstract Introduction: Clinical trials have demonstrated that the new oral anticoagulants (NOACs), dabigatran, rivaroxaban, and apixaban are either superior or non-inferior to standard therapies/placebo for the treatment of nonvalvular atrial fibrillation (NVAF) and venous thromboembolism (VTE). This study estimated and compared the medical costs from a U.S. payer perspective that may be potentially avoided when NOACs are used instead of standard therapies/placebo for the treatment of patients with NVAF or VTE. Methods: Event rates of efficacy and safety clinical endpoints as defined in clinical trials (Table), were obtained from published trial data. Medical cost avoidances associated with NOAC usage vs. standard therapies/placebo for NVAF patients, acute VTE treatment patients, and extended VTE treatment patients were derived from previous publications. All costs were inflation adjusted to 2013 cost level. A hypothetical health plan population with 1 million members in 2014 was used to estimate and compare the NVAF and VTE combined medical cost avoidances for patients treated with NOACs vs. standard therapies/placebo. Prevalence rates of NVAF and VTE were derived from published literature. The same usage rate for each NOAC was assumed for comparison purpose. The medical cost avoidances are also projected in the years 2015-2018 and compared among the NOACs. Results: In 2014, in the hypothetical population of one million insured lives, the medical costs were projected to be reduced by -$3.0, -$2.1, and -$7.3 million for NVAF patients treated with dabigatran, rivaroxaban, and apixaban, respectively; by -$0.7, -$2.2, and -$4.1 million for patients treated for acute VTE with dabigatran, rivaroxaban, and apixaban, respectively; and by -$6.3, -$6.6, -$9.6, and -$9.5 million for VTE patients treated for extended periods with dabigatran, rivaroxaban, 2.5 mg apixaban, and 5.0 mg apixaban, respectively (2 arms with different apixaban dosages were included in extended VTE treatment trial). In 2014, for the combined NVAF and VTE patient populations, within the hypothetical population of one million insured lives, medical costs were projected to be reduced by -$10.0, -$10.9, -$21.0, and -$21.0 million for dabigatran, rivaroxaban, 2.5 mg apixaban, and 5.0 mg apixaban, respectively. In the model, the reductions in medical costs associated with usage of the NOACs were projected to steadily increase in the years 2015 to 2018 (Figure). Conclusions: Medical costs are reduced, when any of the three NOACs are used instead of standard therapy/placebo for the treatment of NVAF or VTE. Apixaban is associated with the greatest reduction in medical costs, which is driven by medical cost reductions associated with both efficacy and safety endpoints among patients with NVAF or VTE. Further evaluation may be needed to validate these results in the real-world setting. Table 1 Clinical Trials from which Clinical Event Rates were Obtained Trial Drug Indication RE-LY Dabigatran Nonvalvular atrial fibrillation ROCKET-AF Rivaroxaban Nonvalvular atrial fibrillation ARISTOTLE Apixaban Nonvalvular atrial fibrillation RE-COVER I Dabigatran Acute venous thromboembolism RE-COVER II Dabigatran Acute venous thromboembolism EINSTEIN-Pooled Rivaroxaban Acute venous thromboembolism AMPLIFY Apixaban Acute venous thromboembolism RE-SONATE Dabigatran Extended venous thromboembolism EINSTEIN-EXT Rivaroxaban Extended venous thromboembolism AMPLIFY-EXT Apixaban Extended venous thromboembolism Figure 1 Figure 1. Disclosures Amin: Bristol-Myers Squibb, Pfizer: Consultancy. Off Label Use: Apixaban for the indication of VTE.. Bruno:Bristol-Myers Squibb: Employment, Equity Ownership. Trocio:Pfizer: Employment, Equity Ownership. Lin:Bristol-Myers Squibb, Pfizer: Consultancy, Research Funding. Lingohr-Smith:Bristol-Myers Squibb, Pfizer: Consultancy, Research Funding.

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Stroke and thromboembolic event rates in atrial fibrillation according to different guideline treatment thresholds: A nationwide cohort study

Scientific Reports ◽

10.1038/srep27410 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 37

Author(s):

Peter Brønnum Nielsen ◽

Torben Bjerregaard Larsen ◽

Flemming Skjøth ◽

Thure Filskov Overvad ◽

Gregory Y. H. Lip

Keyword(s):

Atrial Fibrillation ◽

Cohort Study ◽

Thromboembolic Event ◽

Treatment Thresholds ◽

Event Rates

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Abstract 2: Comparative Effectiveness and Safety of Anticoagulant Therapy With Warfarin, Dabigatran, Apixaban, or Rivaroxaban in Patients With Nonvalvular Atrial Fibrillation

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.9.suppl_2.2 ◽

2016 ◽

Vol 9 (suppl_2) ◽

Author(s):

Gboyega Adeboyeje ◽

Gosia Sylwestrzak ◽

Jeff White ◽

Alan Rosenberg ◽

Jacob Abarca ◽

...

Keyword(s):

Atrial Fibrillation ◽

Major Bleeding ◽

Thromboembolic Event ◽

Relative Effectiveness ◽

Bleeding Event ◽

Bleeding Risk ◽

The United States ◽

Baseline Risk ◽

Nonvalvular Atrial Fibrillation ◽

Significant Difference

Background: The efficacy and safety of novel oral anticoagulants (NOACs) as alternatives to warfarin therapy in nonvalvular atrial fibrillation (NVAF) patients have been studied in randomized trials. Given the increasing use of NOACs, additional data is required to assess the relative effectiveness and safety of anticoagulation with warfarin, dabigatran, apixaban, or rivaroxaban therapy in real-world settings in the United States (U.S). Methods: A retrospective cohort study design was used to analyze data from a U.S. commercial claims database of > 38 million members. Study population included new users of warfarin, dabigatran, apixaban, or rivaroxaban aged ≥ 18 years with ≥ 2 diagnoses of NVAF from November 2010 to February 2015. The primary effectiveness outcome was a composite of thromboembolic event or stroke; the primary safety outcome was major bleeding event requiring hospitalization. Cox proportional hazards models with inverse probability of treatment weighting (IPTW) were used to compare event rates between NOAC and warfarin users, and among NOAC users. Results: In the final NVAF cohort studied, there were 23,431 warfarin, 8,539 dabigatran, 3,689 apixaban, and 8,398 rivaroxaban users. A total of 7,022 primary outcome events and 3,264 safety events were identified. Warfarin users were older than dabigatran, apixaban, or rivaroxaban users (mean: 73 vs 66 vs 69 vs 67 years). After IPTW, all treatment groups were balanced on all baseline risk factors including stroke and bleeding risk. Compared to warfarin, NOAC users had fewer thromboembolic events or strokes: dabigatran (hazard ratio HR, 0.77 [95% CI: 0.72 - 0.82]), apixaban (HR, 0.73 [CI: 0.65 - 0.82]), and rivaroxaban (HR, 0.80 [CI: 0.75 - 0.86]). Additionally, dabigatran ([HR], 0.67 [CI: 0.60 - 0.76]), and apixaban users (HR, 0.52 [CI: 0.41 - 0.67) experienced fewer major bleeding events compared to warfarin users. No significant difference was found in major bleeding risk between rivaroxaban (HR, 1.00 [CI: 0.89 - 1.12]) and warfarin users. All three NOAC groups had similar risks for thromboembolic event or stroke: dabigatran vs rivaroxaban (HR, 0.96 [CI: 0.88 - 1.05]); apixaban vs rivaroxaban (HR, 0.91 [CI: 0.80 - 1.04]); dabigatran vs apixaban (HR, 1.05 [CI: 0.93 - 1.19]). However, compared to rivaroxaban users, major bleeding risk was 33% and 48% lower in dabigatran and apixaban users respectively (HR, 0.67[CI: 0.58 - 0.78]) and HR, 0.52 [CI: 0.40 - 0.68]). Conclusions: Our results demonstrated a lower risk of a thromboembolic event or stroke among dabigatran, apixaban, or rivaroxaban users compared to warfarin users. Among NOACs, risks of a thromboembolic event or stroke were similar. Further studies are needed to clarify the finding of a higher major bleeding risk in warfarin and rivaroxaban users.

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Dabigatran and warfarin in nonvalvular atrial fibrillation or atrial flutter in outpatient clinic practice in Brazil

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20190005 ◽

2019 ◽

Vol 77 (2) ◽

pp. 80-83 ◽

Cited By ~ 1

Author(s):

Jean Michell Correia Monteiro ◽

Daniel Lordelo San-Martin ◽

Beatriz Carneiro Gondim Silva ◽

Ian Felipe Barbosa Souza ◽

Jamary Oliveira Filho ◽

...

Keyword(s):

Atrial Fibrillation ◽

Atrial Flutter ◽

Major Bleeding ◽

Thromboembolic Event ◽

Minor Bleeding ◽

Nonvalvular Atrial Fibrillation ◽

Warfarin Group ◽

Clinic Practice ◽

Prior Stroke

ABSTRACT Objectives: To compare warfarin and dabigatran for thromboembolic event prevention in patients with nonvalvular atrial fibrillation or atrial flutter. Methods: This was a retrospective cohort of participants with nonvalvular atrial fibrillation or atrial flutter using either warfarin or dabigatran in a reference center in Brazil. Results: There were 112 patients (mean age 65.5 years), with 55.3% using warfarin. The median duration of follow-up was 1.9 years for warfarin and 1.6 years for dabigatran (p = 0.167). Warfarin patients had a higher median of medical appointments per year (8.3 [6.8-10.4] vs 3.1 [2.3-4.2], p < 0.001) and the frequency of minor bleeding was more than four times higher (17.7% vs 4.0%, p = 0.035). Among patients with prior stroke, those using warfarin had 2.6 times more medical appointments for person-years of follow-up (8.5 vs 3.3). There was no major bleeding or embolic event during follow-up period. Conclusion: The dabigatran group had a lower frequency of minor bleeding and number of medical appointments than the warfarin group, without more embolic events or major bleeding.

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Abstract 158: Exposure to Warfarin and the Risks of Stroke and Bleeding Events among Patients with Non-Valvular Atrial Fibrillation: Real-World vs. Clinical Trial

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.5.suppl_1.a158 ◽

2012 ◽

Vol 5 (suppl_1) ◽

Author(s):

Alpesh Amin ◽

Luke Boulanger ◽

Elyse Gatt ◽

Dinara Makenbaeva ◽

Michael Stokes ◽

...

Keyword(s):

Atrial Fibrillation ◽

Real World ◽

Index Date ◽

Population Exposure ◽

Bleeding Events ◽

Nonvalvular Atrial Fibrillation ◽

The Real ◽

Pharmacy Claims ◽

Increased Risk ◽

Event Rates

INTRODUCTION: While recent randomized controlled trials (RCTs) have examined safety and efficacy of apixaban versus warfarin in stroke prevention among patients with nonvalvular atrial fibrillation (NVAF), real-world (RW) event rates may differ from the RCT setting. HYPOTHESIS: In a managed care, NVAF population exposure to warfarin is associated with a decreased risk of stroke and increased risk of bleed relative to non-exposure, but both stroke and bleed rates remain higher than those observed in RCT settings. METHODS: Using a retrospective cohort design, we selected patients aged ≥18 years with diagnosis of NVAF during 2007- 2009 from a Medco population of both U.S. commercial and Medicare health plans. The first claim with an AF diagnosis was defined as the study index date. Pharmacy claims were used to define periods of warfarin exposure following the study index date. Stroke and bleed events occurring during follow-up were identified using diagnosis codes on the medical claims and categorized according to occurrence during warfarin exposure or no exposure and according to patient baseline CHADS2 risk to address differences in population risk. RESULTS: Of the 37,878 patients meeting the study criteria, the mean age was 75 years (SD=8.6), and 53% were male. Among the 66% of patients with at least one prescription for warfarin, the total person-time of warfarin exposure was 41,515 years. Compared to rates occurring in two recent RCTs of warfarin exposed (ARISTOTLE) and warfarin unexposed (AVERROES; aspirin treated) patients, stroke and bleed event rates for NVAF patients in the real-world were higher overall and within each CHADS2 group. CONCLUSIONS: While in the real world warfarin use was associated with a reduction in stroke rates and an increase in bleed rates, the rate of events in real world patients relative to their RCT counterparts were higher. The absolute impact of novel agents, such as apixaban, in the real world may be greater than in RCT setting if the relative risk reductions versus alternatives from RCTs persist in the real world.

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Preventing Stroke in Patients with Atrial Fibrillation - Evidence Update for Clinicians

10.25302/eu13.2020.5 ◽

2020 ◽

Author(s):

Keyword(s):

Atrial Fibrillation ◽

General Population ◽

Major Bleeding ◽

Anticoagulation Therapy ◽

Bleeding Risk ◽

Nonvalvular Atrial Fibrillation ◽

Administration Regimen ◽

Increased Risk ◽

All Cause Mortality

Patients with atrial fibrillation have a higher risk for stroke than the general population, and that risk increases markedly with age. Anticoagulation therapy lowers the risk of stroke and improves all-cause mortality. Warfarin has been the mainstay of anticoagulation therapy for decades but has an increased risk of major bleeding and requires a complicated administration regimen. A recent update of research adds to the evidence about the relative benefits and harms of newer anticoagulation therapies and tools to predict stroke related to atrial fibrillation and bleeding risk. This evidence on the newer therapies, along with recently updated guidelines on managing nonvalvular atrial fibrillation, can help inform clinician and patient decisions on anticoagulant use and may potentially reduce the risk of stroke and its consequences.

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Clinical Events with Edoxaban in South Korean and Taiwanese Atrial Fibrillation Patients in Routine Clinical Practice

Journal of Clinical Medicine ◽

10.3390/jcm10225337 ◽

2021 ◽

Vol 10 (22) ◽

pp. 5337

Author(s):

Eue-Keun Choi ◽

Wei-Shiang Lin ◽

Gyo-Seung Hwang ◽

Paulus Kirchhof ◽

Raffaele De Caterina ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Clinical Practice ◽

Cardiovascular Death ◽

Outcome Data ◽

Routine Clinical Practice ◽

Nonvalvular Atrial Fibrillation ◽

Asian Patients ◽

Clinical Events ◽

Event Rates

Edoxaban is approved for stroke prevention in nonvalvular atrial fibrillation (AF) patients in numerous countries. Outcome data are sparse on edoxaban treatment in AF patients from routine clinical practice, especially in Asian patients. Global ETNA (Edoxaban in rouTine cliNical prActice) is a noninterventional study that integrates data from patients from multiple regional registries into one database. Here, we report the 1-year clinical events from AF patients receiving edoxaban in South Korea and Taiwan. Clinical events assessed included bleeding, strokes, systemic embolic events, transient ischemic attacks (TIAs), and all-cause and cardiovascular death. Overall, 2677 patients (mean (range) age 72 (66–78) years, male 59.7%, mean CHA2DS2-VASc score ± standard deviation 3.1 ± 1.4) were treated with 60 or 30 mg edoxaban and had 1-year follow-up data. The annualized event rates for major bleeding and clinically relevant non-major (CRNM) bleeding were 0.78% and 0.47%, respectively. Annualized event rates for ischemic stroke and hemorrhagic stroke were 0.90% and 0.19%, respectively. Event rates for major and CRNM bleeding and rates of ischemic stroke and TIA were higher in Taiwanese patients than in Korean patients. Event rates were low and similar to those found in other studies of edoxaban in Korean and Taiwanese AF patients, thus supporting the safety and effectiveness of edoxaban in this population.

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