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To compare the risk of stroke and systemic embolism (SE) among patients with nonvalvular atrial fibrillation (NVAF) who abandoned their first direct oral anticoagulant (DOAC) fill ("abandoners") relative to patients who continued DOACs beyond the first fill ("continuers"). In this retrospective longitudinal study, adults with NVAF prescribed DOACs were selected from Symphony Health, an ICON plc Company, PatientSource, 1 April 2017 to 31 October 2020. A 90-day landmark period following the first DOAC fill was used to classify patients as abandoners or continuers. Inverse probability of treatment weighting was used to balance baseline characteristics between cohorts. Time to ischemic stroke/SE was described and compared between cohorts using weighted Kaplan-Meier and Cox proportional hazard models from the end of the landmark period until end of clinical activity or data. After weighting, 200,398 and 211,352 patients comprised the abandoner and continuer cohorts, respectively. The mean duration of follow-up was 14.9 and 15.7 months, respectively. At 12 months of follow-up, the probability of ischemic stroke/SE was 1.34% in the abandoner cohort and 1.00% in the continuer cohort; the risk of ischemic stroke/SE was 35% higher in the abandoner versus continuer cohort (hazard ratio [95% confidence interval] = 1.35 [1.20, 1.51]; p < 0.0001). Patients with NVAF who abandoned the first DOAC fill had significantly higher risk of ischemic stroke/SE compared to patients who continued therapy beyond the first fill. There is an unmet need for better access to DOACs so that the long-term risk of poor outcomes may be minimized. [ABSTRACT FROM AUTHOR]

It is unclear whether 90-day supply fills with rivaroxaban result in better adherence and persistence compared to 30-day supply fills. We assessed patients' adherence and persistence to rivaroxaban at 12- and 24-months in nonvalvular atrial fibrillation (NVAF) patients whose rivaroxaban prescriptions were filled every 30- vs. 90-days. Using the IBM MarketScan Commercial and Medicare Supplemental data sets, we identified adult NVAF patients with ≥12-months of continuous insurance coverage who filled a prescription in May 2018 and their immediate subsequent prescription for rivaroxaban for the same days' supply. We propensity score-matched 30- and 90-day rivaroxaban interval fill patients and compared the percentage with a proportion of days covered (PDC) ≥80%, mean PDC, and percentage persistent to rivaroxaban therapy over 12- and 24-months of follow-up. Following propensity score matching, 2237 patients were included in the rivaroxaban 30- and 90-day supply fill cohorts. The proportion of patients with a PDC ≥80% was greater in the 90-day vs. 30-day cohort at both 12-months (odds ratio [OR] = 1.75, 95% confidence interval [CI] = 1.54–1.97) and 24-months (OR = 1.78, 95%CI = 1.58–2.00), as were mean PDC values (absolute difference in mean PDC = 9.4%, 95%CI = 8.2–10.7% at 12-months and 11.2%, 95%CI = 9.5–12.9% higher at 24-months, respectively). Persistence to rivaroxaban was not found to significantly differ between the 30- and 90-day supply cohorts at 12- or 24-months (assuming a 30-day permissible gap); however, greater persistence was observed with 90-day fills at both time points when a 14-day gap was utilized (HR = 1.22, 95%CI = 1.10–1.36 at 12-months and HR = 1.12, 95%CI = 1.02–1.22 at 24-months). Dispensing 90-day supply fills with rivaroxaban appears to increase the proportion of patients achieving acceptable (PDC ≥80%) adherence as well as mean adherence compared to 30-day supply fills. Ninety-day rivaroxaban fills may also result in improved persistence vs. 30-day fills. [ABSTRACT FROM AUTHOR]

Health-related quality of life (HRQL) is a key factor in making anticoagulant treatment decisions. The objective of this study was to assess the HRQL of patients with nonvalvular atrial fibrillation by treatment type: direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs). We carried out a cross-sectional observational study with clinical practice data, gathering demographic and clinical variables. HRQL was measured using the 5-level 5-dimension EuroQol questionnaire (EQ-5D-5L). Differences between the study groups in HRQL as measured by the EQ-5D-5L were analyzed using two-part multivariate regression models. First, using logistic regression, the adjusted probability, p(x), of having perfect health was estimated in each subgroup. Secondly, generalized linear models were used to estimate mean disutility values, w(x), in a population that does not have perfect health, i.e. utility less than 1 or 1-w(x). We recruited 333 patients, of whom 126 were on DOACs and 207 on VKAs. A significant difference was observed in the EQ-5D-5L anxiety/depression dimension, with a higher percentage of patients classified in the 'no problems' category in the DOAC group. The same type of analysis did not identify significant differences in any of the other dimensions (mobility, self-care, usual activities or pain/discomfort). In the multivariate model, utility was significantly higher in the DOAC group than in the VKA group, although the difference was small (0.0121). This difference is attributable to patients on DOACs having less anxiety/depression. Patients treated with DOACs report a slightly better quality of life than those treated with VKAs. [ABSTRACT FROM AUTHOR]

Objective: To compare the risk of hospitalization and costs associated with major bleeding (MB) or stroke/systemic embolism (SE) among elderly patients with nonvalvular atrial fibrillation (NVAF) who initiated apixaban then switched to another oral anticoagulant (OAC) vs. those who continued with apixaban treatment. Methods: NVAF patients (≥65 years) initiating apixaban were identified from the Humana database (1 January 2013-30 September 2017) and grouped into switcher and continuer cohorts. For switchers, the earliest switch from apixaban to another OAC was defined as the index event/date. A random date during apixaban treatment was selected as the index date for continuers. Patients were followed from index date to health plan disenrollment or 31 December 2017, whichever was earlier. Multivariable regression analyses were used to examine the association of switchers vs. continuers with risk of MB-related or stroke/SE-related hospitalization and healthcare costs during follow-up. Results: Of 7858 elderly NVAF patients included in the study, 14% (N = 1110; mean age: 78 years) were switchers; 86% (N = 6748; mean age: 79 years) were continuers. Apixaban switchers vs. continuers had significantly greater risk of MB-related hospitalization (hazard ratio [HR]: 2.00; 95% CI: 1.52-2.64; p < .001) during follow-up; risk of stroke/SE hospitalization did not differ significantly (HR: 1.36, 95% CI: 0.89-2.06, p = .154). MB- and stroke/SE-related medical costs were higher for switchers vs. continuers, although total all-cause healthcare costs were similar. Conclusion: Elderly patients with NVAF in the US who continued with apixaban treatment had a lower risk of MB-related hospitalization and lower MB- and stroke/SE-related medical costs compared to patients who switched to another OAC. [ABSTRACT FROM AUTHOR]

Introduction: Several comparative real-world effectiveness studies on direct oral anticoagulants (DOACs) have been conducted, but an overview of the available evidence remains to be developed, which could provide a better understanding of the value of DOACs relative to vitamin K antagonists (VKAs).Areas Covered: A systematic literature review was conducted on the available real-world evidence (RWE) of three DOACs (rivaroxaban, dabigatran, and apixaban) compared with VKAs (e.g. warfarin), in patients with nonvalvular atrial fibrillation (NVAF).This systematic literature review included RWE published up to December 2016. Studies with > 50 patients reporting on incident and prevalent NVAF cases were included. The following databases were searched: Medline, Embase, and the Cochrane Library. Outcomes of interest included thromboembolic events, all-cause mortality, bleeding events, and nonpersistence. Of the 562 RWE DOACs articles retrieved, 49 presented results for rivaroxaban versus VKAs, 79 for dabigatran versus VKAs, and 18 for apixaban versus VKAs. Substantial heterogeneity was found across patient population, outcome definition, and follow-up period. Major bleeding, ischemic stroke, and intracranial hemorrhage were the most frequent outcomes analyzed.Expert Commentary: Overall, the RWE studies were aligned with the Phase 3 trials. However, conflicting results were reported for several outcomes of interest. [ABSTRACT FROM AUTHOR]

Objective: To investigate the risk of bleeding events and stroke/systemic embolism (SE) among Japanese patients with nonvalvular atrial fibrillation (NVAF), focusing on the initial dosage of apixaban and patient age.Methods: This retrospective cohort study used de-identified electronic health records based claims data from 314 acute-care hospitals in Japan. NVAF patients newly initiated on warfarin or apixaban, with no prescription during the 180-day blanking period, were eligible. Patients were allocated to receive warfarin or 5 or 2.5 mg twice daily (BID) apixaban. One-to-one propensity-score matching was used to balance patient characteristics between apixaban and warfarin.Results: Among 31,006 eligible patients, 11,972 matched pairs were identified for apixaban versus warfarin. Mean age ± standard deviation was 77.7 ± 10.0 and 77.6 ± 10.0 years and CHADS2 score was 2.2 ± 1.4 and 2.2 ± 1.4 for warfarin and apixaban, respectively. In the apixaban cohort, 39.4% of patients received the standard dose (5 mg BID) and 60.6% received the reduced dose (2.5 mg BID). Incidence rates (events per 100 person-years) of major bleeding, any bleeding and stroke/SE were 3.7, 23.1 and 3.1, and 2.5, 18.6 and 2.0 for warfarin and apixaban cohorts, respectively. Apixaban was associated with a significantly lower risk of any bleeding (hazard ratio [HR] 0.809, 95% confidence interval [CI] 0.731-0.895; p < .001), major bleeding (HR 0.655, 95% CI 0.505-0.849; p = .001) and stroke/SE (HR 0.637, 95% CI 0.478-0.850; p = .002).Conclusions: Our observational data from clinical practice broadly confirms the safety and efficacy results of pivotal randomized controlled trials of apixaban for stroke prevention among NVAF patients. [ABSTRACT FROM AUTHOR]

Objectives: Due to the high cost of nonvalvular atrial fibrillation (NVAF), this condition may be a suitable candidate for condition-specific bundled payments. This paper evaluates the healthcare cost of NVAF and uses common bleeding and stroke risk scores (HAS-BLED and CHA2DS2-VASc) to explore the risk-based healthcare cost differences among NVAF patients.Methods: MarketScan claims of NVAF patients (ICD-9-CM code 427.31) were analyzed from January 2010 to April 2015. These claims feature more than 196 million covered lives and more than 300 contributing employers and 25 contributing health plans. A retrospective cohort design was used to assess episodes of care costs among patients with NVAF. Previously and newly diagnosed NVAF patients were selected from adult patients with ≥2 diagnoses of NVAF, and without valvular disease. Total all-cause healthcare costs at 1 year were stratified by stroke (CHA2DS2-VASc) and bleeding (HAS-BLED) risk scores. Study data was extracted in the MarketScan Commercial Claims and Encounters Database (Commercial Database) and the MarketScan Medicare Supplemental and Coordination of Benefits Database (Medicare Supplemental Database).Results: Mean all-cause 1 year cost of care based on stroke risk (CHA2DS2-VASc) varied from $15,703 to $59,163 for previously diagnosed and $25,992 to $62,458 for newly diagnosed NVAF. Similarly, mean cost varied base on bleeding risk (HAS-BLED) for previously and newly diagnosed NVAF from $17,950 to $57,029 and $26,356 to $67,104 respectively.Conclusion: NVAF patients accrue variable healthcare costs. Stroke and bleeding risk should be taken into account during the creation of NVAF payment bundles. [ABSTRACT FROM AUTHOR]

Objective: To compare the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) of elderly (≥65 years of age) nonvalvular atrial fibrillation (NVAF) patients initiating apixaban vs. rivaroxaban, dabigatran, or warfarin.Methods: NVAF patients with Medicare Advantage coverage in the US initiating oral anticoagulants (OACs, index event) were identified from the Humana database (1 January 2013-30 September 2015) and grouped into cohorts depending on OAC initiated. Propensity score matching (PSM), 1:1, was conducted among patients treated with apixaban vs. each other OAC, separately. Rates of S/SE and MB were evaluated in the follow-up. Cox regressions were used to compare the risk of S/SE and MB between apixaban and each of the other OACs during the follow-up.Results: The matched pairs of apixaban vs. rivaroxaban (n = 13,620), apixaban vs. dabigatran (n = 4654), and apixaban vs. warfarin (n = 14,214) were well balanced for key patient characteristics. Adjusted risks for S/SE (hazard ratio [HR] vs. rivaroxaban: 0.72, p = .003; vs. warfarin: 0.65, p < .001) and MB (HR vs. rivaroxaban: 0.49, p < .001; vs. warfarin: 0.53, p < .001) were significantly lower during the follow-up for patients treated with apixaban vs. rivaroxaban and warfarin. Adjusted risks for S/SE (HR: 0.78, p = .27) and MB (HR: 0.82, p = .23) of NVAF patients treated with apixaban vs. dabigatran trended to be lower, but did not reach statistical significance.Conclusions: In the real-world setting after controlling for differences in patient characteristics, apixaban is associated with significantly lower risk of S/SE and MB than rivaroxaban and warfarin, and a trend towards better outcomes vs. dabigatran among elderly NVAF patients in the US. [ABSTRACT FROM AUTHOR]

Introduction: With the rising prevalence of nonvalvular atrial fibrillation (NVAF) in the general population, the development of new drugs for prevention of thromboembolic events is essential. Non-vitamin K antagonist oral anticoagulants (NOACs) have been shown to present a number of advantages over conventionally used agents, such as predictable pharmacokinetics and no requirement for continuous anticoagulant monitoring. The most recently approved NOAC for the NVAF indication is edoxaban. Several subgroup analyses from the edoxaban phase III ENGAGE AF-TIMI 48 trial have now been published, alongside meta-analysis data comparing the four currently approved NOACs. Consequently, an updated review of the literature is merited. Areas covered: A PubMed search using the terms ‘edoxaban’, ‘non-vitamin K antagonist oral anticoagulant’, ‘ENGAGE AF-TIMI 48’, and ‘atrial fibrillation’ was performed and results screened for the most relevant English language publications. The market position, pharmacological profile, clinical efficacy, safety and tolerability of edoxaban are presented and discussed. Expert commentary: Edoxaban has been shown to have an efficacy similar or superior to that of warfarin, with a potentially lower risk of major bleeding and predictable, dose-dependent pharmacology. In order to clarify its position within the NOAC market, head-to-head comparative studies are required. [ABSTRACT FROM AUTHOR]

Background:Little data exists regarding the effectiveness and safety of rivaroxaban or apixaban versus warfarin in nonvalvular atrial fibrillation (NVAF) patients treated outside of clinical trials. Methods:This was a retrospective study using MarketScan claims from January 2012 to October 2014. We included adults, newly initiated on rivaroxaban, apixaban or warfarin, with a baseline CHA2DS2-VASc score ≥2, ≥2 diagnosis codes for NVAF and ≥180 days of continuous medical and prescription benefits. Patients with a prior stroke, systemic embolism or intracranial hemorrhage (ICH) were excluded. Eligible rivaroxaban or apixaban users were 1:1 propensity-score matched individually to warfarin users. Cox regression was performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for rivaroxaban and apixaban versus warfarin for the combined endpoint of ischemic stroke or ICH and each endpoint individually. Results:Upon matching 11,411 rivaroxaban to 11,411 warfarin users, rivaroxaban was associated with a significant reduction of the combined endpoint of ischemic stroke or ICH versus warfarin (HR = 0.61, 95% CI = 0.45–0.82). ICH was significantly (HR = 0.53, 95% CI = 0.35–0.79) and ischemic stroke nonsignificantly reduced (HR = 0.71, 95% CI = 0.47–1.07) by rivaroxaban versus warfarin. After matching 4083 apixaban and 4083 warfarin users, apixaban was found to nonsignificantly reduce the combined endpoint of ischemic stroke or ICH versus warfarin (HR = 0.63, 95% CI = 0.35–1.12) and to reduce ICH risk (HR = 0.38, 95% CI = 0.17–0.88). Ischemic stroke risk was nonsignificantly increased with apixaban (HR = 1.13, 95% CI = 0.49–2.63) versus warfarin. Limitations:Sample size and number of combined events observed were relatively small. Residual confounding could not be ruled out. Conclusions:Rivaroxaban and apixaban were associated with less ICH than warfarin and both are likely associated with reductions in the combined endpoint. Further investigation to validate the numerically higher rate of ischemic stroke with apixaban versus warfarin is required. [ABSTRACT FROM PUBLISHER]

Numerous real-world studies estimating major bleeding rates in rivaroxaban patients with nonvalvular atrial fibrillation have been published. We performed a meta-analysis to better quantify the rates of different types of major bleeding seen with rivaroxaban in observational studies. The pooled rates of major bleeding with rivaroxaban were generally low and consistent with those reported in its pivotal randomized controlled trial. [ABSTRACT FROM AUTHOR]

Objective: Clinical trials have demonstrated that direct oral anticoagulants (DOACs) are efficacious in reducing stroke risk among patients with nonvalvular atrial fibrillation (NVAF) with differences in the reduction of bleeding risks vs. warfarin. The objective of this study was to assess bleeding-related hospital readmissions among hospitalized NVAF patients treated with dabigatran, rivaroxaban, and apixaban in the US.Research Design and Methods: Patients (≥18 years) with a discharge diagnosis of NVAF who received apixaban, dabigatran, or rivaroxaban during hospitalization were identified from the Premier Hospital database (1 January 2012-31 March 2014) and the Cerner Health Facts hospital database (1 January 2012-31 August 2014). Patients identified from each database were analyzed separately and grouped into three cohorts depending on which DOAC was received. Patient characteristics, hospital resource use and costs, and frequency of readmissions within 1 month were evaluated.Results: Among study populations identified from the Premier database (N = 74,730) and the Cerner database (N = 14,201), patients who received apixaban were older, had greater comorbidity, and had higher stroke and bleeding risks. After controlling for patient characteristics, including comorbidity and stroke and bleeding risks, compared with patients who received apixaban during their index hospitalizations, the odds of bleeding-related hospital readmissions were significantly greater by 1.4-fold (p < 0.01) for patients who received rivaroxaban and 1.2-fold (p = 0.16) numerically greater for patients who received dabigatran among patients identified from the Premier Hospital database. Among patients in the Cerner Health Facts hospital database, bleeding-related hospital readmissions were significantly greater by 1.6-fold (p = 0.04) for patients who received rivaroxaban and 1.3-fold (p = 0.30) numerically greater for patients who received dabigatran compared to patients who received apixaban.Limitations: No causal relationship between treatment and outcomes can be concluded.Conclusions: NVAF patients using different DOACs had different characteristics, including stroke and bleeding risks. Use of rivaroxaban, compared to apixaban was associated with significantly greater risk of bleeding-related readmissions across two database claims analyses. [ABSTRACT FROM AUTHOR]

Background: Warfarin is efficacious for reducing stroke risk among patients with nonvalvular atrial fibrillation (NVAF). However, the efficacy and safety of warfarin are influenced by its time in therapeutic range (TTR).Objective: To assess differences in healthcare resource utilization and costs among NVAF patients with low (<60%) and high (≥60%) warfarin TTRs in an integrated delivery network (IDN) setting.Methods: Patients with NVAF were identified from an electronic medical record database. Patients were required to have ≥6 international normalized prothrombin time ratio (INR) tests. NVAF patients were grouped into two cohorts: those with warfarin TTR <60% (low TTR) and those with warfarin TTR ≥60% (high TTR). Healthcare resource utilization and costs were evaluated during a 12 month follow-up period. Multivariable regressions were used to assess the impact of different warfarin TTRs on healthcare costs.Results: Among the study population, greater than half (54%, n = 1595) had a low TTR, and 46% (n = 1356) had a high TTR. Total all-cause healthcare resource utilization was higher among patients in the low TTR cohort vs. the high TTR cohort (number of encounters: 70.2 vs. 56.1, p < 0.001). After adjusting for patient characteristics, total all-cause healthcare costs and stroke-related healthcare costs were $2398 (p < 0.001) and $687 (p = 0.02) higher, respectively, for patients in the low TTR cohort vs. the high TTR cohort.Limitations: In this retrospective study, we were only able to evaluate the association and not the causality between healthcare resource utilization and costs with the different warfarin TTRs.Conclusion: Many warfarin-treated NVAF patients have a low warfarin TTR. NVAF patients with low vs. patients with high warfarin TTR used healthcare resources to a greater extent, which was reflected in higher healthcare costs. [ABSTRACT FROM AUTHOR]

Background: Warfarin is effective for stroke prevention in patients with atrial fibrillation (AF), but international normalized ratio (INR) levels fluctuate and frequent monitoring is necessary. Methods: This study used data from a large anticoagulation management service database to analyze the relationship between INR stabilization and warfarin utilization for >1 year in patients with nonvalvular AF (NVAF). Anticoagulation records from a large US electronic database collected from 2006 to 2010 were analyzed. Results: Patients with NVAF and ≥3 INR values in the dataset were identified (n= 15,276). INR stabilization was defined as the first three consecutive INR values between 2.0 and 3.0 after warfarin initiation. One quarter of patients (n=3809) failed to reach INR stabilization. After initial stabilization, 30% of subsequent INR values were out of range. The mean (±standard deviation [SD]) follow-up time from stabilization to the end of study for these patients was 494.2±418.1 days. Age≥75 years (odds ratio [OR]=1.17, 95% confidence interval [CI]=1.08-1.27), hypertension (OR=1.19, 95% CI=1.10-1.29), or prior stroke (OR=1.29, 95% CI=1.04-1.61) were positively associated with achieving stabilization; heart failure was negatively associated with stabilization (OR=0.78, 95% CI=0.70-0.87). Male gender (p<0.0001) and hypertension were associated with earlier stabilization (p=0.0013); heart failure was associated with later stabilization (p=0.0098). Patients who achieved INR stabilization within 1 year were 10 times more likely to remain on warfarin than patients who did not achieve it. Limitations: Observational data may contain incomplete records. Data on adherence, concurrent medications, vitamin K intake, genotype, reasons for discontinuation of monitoring, and patient outcomes were not available in the dataset. The study findings were generalizable only to patients with AF who were managed by anticoagulation clinics. Conclusion: Given the importance of stroke prevention among patients with AF, the potential for unpredictable INR patterns should be carefully considered during clinical decision-making. [ABSTRACT FROM AUTHOR]

The article discusses a study that evaluated real-world safety, effectiveness, and persistence associated with rivaroxaban and warfarin in nonvalvular atrial fibrillation patients. Topics discussed include the analysis of Healthcare claims from Symphony Health Solutions' Patient Transactional Datasets from May 2011 to July 2012, classification of patients with prior use of warfarin, and demographic and clinical attributes of rivaroxaban and warfarin users.