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      Comparison of Drug Switching and Discontinuation Rates in Patients with Nonvalvular Atrial Fibrillation Treated with Direct Oral Anticoagulants in the United States

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          Abstract

          Introduction

          Continuous usage of direct oral anticoagulants (DOACs) among nonvalvular atrial fibrillation (NVAF) patients is essential to maintain stroke prevention. We examined switching and discontinuation rates for the three most frequently initiated DOACs in NVAF patients in the USA.

          Methods

          Patients who initiated apixaban, rivaroxaban, or dabigatran (index event/date) were identified from the Pharmetrics Plus claims database (Jan 1, 2013–Sep 30, 2016, includes patients with commercial and Medicare coverage) and grouped into cohorts by index DOAC. Patients were required to have a diagnosis of NVAF and continuous health plan enrollment for 12 months prior to the index date (baseline period) and at least 3 months during the follow-up period. Drug switching rates to any other DOAC or warfarin and index DOAC discontinuation rate were evaluated separately with descriptive statistics, Kaplan–Meier analysis, and multivariable Cox regression analysis.

          Results

          Of the NVAF study population ( n = 41,864), 37% initiated apixaban ( n = 15,352; mean age 62 years), 51% initiated rivaroxaban ( n = 21,250; mean age 61 years), and 13% initiated dabigatran ( n = 5262; mean age 61 years). During the follow-up period, the unadjusted drug switching rates of patients treated with apixaban, rivaroxaban, and dabigatran were 3.6%, 6.3%, and 11.1%, respectively ( p < 0.001 across the three cohorts); while the index DOAC discontinuation rates were 52.8%, 60.3%, and 62.9%, respectively ( p < 0.001). After we controlled for differences in patient characteristics, patients treated with rivaroxaban (HR 1.8; 95% CI 1.6–2.0; p < 0.001) and dabigatran (HR 3.4; 95% CI 3.0–3.8, p < 0.001) had a significantly greater likelihood for drug switching than patients treated with apixaban. Also, both rivaroxaban (HR 1.1; 95% CI 1.1–1.2, p < 0.001) and dabigatran (HR 1.3; 95% CI 1.2–1.3, p < 0.001) treated patients were more likely to discontinue treatment.

          Conclusion

          In the real-world setting, patients with NVAF newly treated with apixaban were less likely to switch or discontinue treatment compared to patients treated with rivaroxaban or dabigatran.

          Funding

          Pfizer and Bristol-Myers Squibb.

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          Most cited references20

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          Estimates of current and future incidence and prevalence of atrial fibrillation in the U.S. adult population.

          Estimates and projections of diagnosed incidence and prevalence of atrial fibrillation (AF) in the United States have been highly inconsistent across published studies. Although it is generally acknowledged that AF incidence and prevalence are increasing due to growing numbers of older people in the U.S. population, estimates of the rate of expected growth have varied widely. Reasons for these variations include differences in study design, covered time period, birth cohort, and temporal effects, as well as improvements in AF diagnosis due to increased use of diagnostic tools and health care awareness. The objective of this study was to estimate and project the incidence and prevalence of diagnosed AF in the United States out to 2030. A large health insurance claims database for the years 2001 to 2008, representing a geographically diverse 5% of the U.S. population, was used in this study. The trend and growth rate in AF incidence and prevalence was projected by a dynamic age-period cohort simulation progression model that included all diagnosed AF cases in future prevalence projections regardless of follow-up treatment, as well as those cases expected to be chronic in nature. Results from the model showed that AF incidence will double, from 1.2 million cases in 2010 to 2.6 million cases in 2030. Given this increase in incidence, AF prevalence is projected to increase from 5.2 million in 2010 to 12.1 million cases in 2030. The effect of uncertainty in model parameters was explored in deterministic and probabilistic sensitivity analyses. Variability in future trends in AF incidence and recurrence rates has the greatest impact on the projected estimates of chronic AF prevalence. It can be concluded that both incidence and prevalence of AF are likely to rise from 2010 to 2030, but there exists a wide range of uncertainty around the magnitude of future trends.
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            Estimation of total incremental health care costs in patients with atrial fibrillation in the United States.

            Detailed information on the cost burden of atrial fibrillation (AF) is limited. To provide an up-to-date estimate of the national cost of AF, we conducted a retrospective, observational cohort study using administrative claims from the MarketScan Commercial and Medicare Supplemental research data bases, 2004 to 2006. Patients aged ≥20 years with ≥1 inpatient or ≥2 outpatient AF diagnoses in 2005 (first diagnosis=index) and ≥12 months' enrollment before and after index were selected. AF patients were propensity score-matched (1:1) with non-AF control subjects. Medical costs (2008 US$), including AF costs, other cardiovascular, and noncardiovascular costs, were examined over 1 year after index. National incremental costs of AF were based on age-/sex-specific AF prevalence projections for 2010. In total, 89 066 AF patients were matched to non-AF control subjects. Over 1 year, 37.5% of AF versus 17.5% of control subjects were hospitalized and 2.1% versus 0.1% died during hospitalization. For AF versus control subjects, mean annual inpatient costs per patient were $7841 versus $2622 (incremental cost, $5218), outpatient medical costs were $9225 versus $5629 ($3596), and outpatient pharmacy costs were $3605 versus $3714 (-$109) (all P<0.001). The total incremental cost of AF was $8705 per patient. The national incremental cost of AF was $26.0 billion (AF, $6.0 billion; other cardiovascular, $9.9 billion; noncardiovascular, $10.1 billion). Cardiovascular costs were based on claims with a primary disease diagnosis and may be underestimates. On the basis of current US age- and sex-specific prevalence data, the national incremental AF cost is estimated to range from $6.0 to $26.0 billion.
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              Effectiveness and Safety of Dabigatran, Rivaroxaban, and Apixaban Versus Warfarin in Nonvalvular Atrial Fibrillation

              Background The introduction of non–vitamin K antagonist oral anticoagulants has been a major advance for stroke prevention in atrial fibrillation; however, outcomes achieved in clinical trials may not translate to routine practice. We aimed to evaluate the effectiveness and safety of dabigatran, rivaroxaban, and apixaban by comparing each agent with warfarin. Methods and Results Using a large US insurance database, we identified privately insured and Medicare Advantage patients with nonvalvular atrial fibrillation who were users of apixaban, dabigatran, rivaroxaban, or warfarin between October 1, 2010, and June 30, 2015. We created 3 matched cohorts using 1:1 propensity score matching: apixaban versus warfarin (n=15 390), dabigatran versus warfarin (n=28 614), and rivaroxaban versus warfarin (n=32 350). Using Cox proportional hazards regression, we found that for stroke or systemic embolism, apixaban was associated with lower risk (hazard ratio [HR] 0.67, 95% CI 0.46–0.98, P=0.04), but dabigatran and rivaroxaban were associated with a similar risk (dabigatran: HR 0.98, 95% CI 0.76–1.26, P=0.98; rivaroxaban: HR 0.93, 95% CI 0.72–1.19, P=0.56). For major bleeding, apixaban and dabigatran were associated with lower risk (apixaban: HR 0.45, 95% CI 0.34–0.59, P<0.001; dabigatran: HR 0.79, 95% CI 0.67–0.94, P<0.01), and rivaroxaban was associated with a similar risk (HR 1.04, 95% CI 0.90–1.20], P=0.60). All non–vitamin K antagonist oral anticoagulants were associated with a lower risk of intracranial bleeding. Conclusions In patients with nonvalvular atrial fibrillation, apixaban was associated with lower risks of both stroke and major bleeding, dabigatran was associated with similar risk of stroke but lower risk of major bleeding, and rivaroxaban was associated with similar risks of both stroke and major bleeding in comparison to warfarin.
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                Author and article information

                Contributors
                christine.l.baker@pfizer.com
                Journal
                Adv Ther
                Adv Ther
                Advances in Therapy
                Springer Healthcare (Cheshire )
                0741-238X
                1865-8652
                29 November 2018
                29 November 2018
                2019
                : 36
                : 1
                : 162-174
                Affiliations
                [1 ]ISNI 0000 0000 8800 7493, GRID grid.410513.2, Pfizer, Inc., ; New York, NY USA
                [2 ]GRID grid.419971.3, Bristol-Myers Squibb, ; Lawrenceville, NJ USA
                [3 ]Novosys Health, Green Brook, NJ USA
                Author information
                http://orcid.org/0000-0001-7532-7399
                Article
                840
                10.1007/s12325-018-0840-8
                6318235
                30499067
                04db7f8c-ecff-4297-8320-92c63e772268
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 18 September 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100002491, Bristol-Myers Squibb;
                Award ID: BMS
                Funded by: Pfizer (US)
                Award ID: Pfizer
                Categories
                Original Research
                Custom metadata
                © Springer Healthcare Ltd., part of Springer Nature 2019

                apixaban,cardiology,dabigatran,direct oral anticoagulants,drug discontinuation,drug switching,nonvalvular atrial fibrillation,rivaroxaban

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