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Chronic kidney disease (CKD) remains a significant global health issue and is a leading cause of mortality worldwide. Patients with CKD have an increased risk of developing atrial fibrillation (AF) and venous thromboembolism (VTE). While direct oral anticoagulants (DOACs) have become a standard of care for anticoagulation (AC) in patients with AF and VTE, the appropriate use of these agents in comorbid kidney impairment warrants detailed discussion. This scientific narrative review summarizes the effectiveness and safety of apixaban use in patients with renal dysfunction by assessing the current published pharmacokinetic, interventional, observational, and guideline data. Apixaban is a highly selective, orally active, direct inhibitor of factor Xa, with well-established pharmacokinetics and consistent clinical outcomes across a broad range of patient populations, including those with kidney impairment. Overall, the scientific literature has shown that apixaban has a favorable clinical efficacy and safety profile compared with vitamin K antagonists for patients with AF or VTE and comorbid kidney impairment. These data support the approved label dosing strategy of apixaban in reducing the risk of stroke/systemic embolism in patients with nonvalvular AF and in treating VTE across all ranges of kidney function. Both clinician experience and knowledge of patient-specific factors may be required in the management of comorbid patients with advanced CKD or those requiring dialysis, as data on these patients are limited.
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Fibrilação Atrial , Inibidores do Fator Xa , Pirazóis , Piridonas , Insuficiência Renal Crônica , Tromboembolia Venosa , Humanos , Piridonas/farmacocinética , Piridonas/efeitos adversos , Piridonas/uso terapêutico , Piridonas/administração & dosagem , Pirazóis/farmacocinética , Pirazóis/uso terapêutico , Pirazóis/efeitos adversos , Pirazóis/administração & dosagem , Inibidores do Fator Xa/farmacocinética , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Inibidores do Fator Xa/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/complicações , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Tromboembolia Venosa/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/epidemiologia , Estudos Observacionais como Assunto , Anticoagulantes/efeitos adversos , Anticoagulantes/farmacocinética , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagemRESUMO
Background: Oral anticoagulants (OACs), such as apixaban and warfarin, are indicated for reducing the risk of recurrent venous thromboembolism (VTE) and are often initiated in the hospital. The aim of this study was to evaluate OAC continuity from inpatient to outpatient settings and the risk of recurrent VTE among patients with an initial event. Methods: This retrospective cohort study utilized hospital charge data and medical and prescription claims from 1 July 2016 to 31 December 2022 to identify adults treated with apixaban or warfarin while hospitalized for VTE. Patients were followed to assess switching or discontinuation post-discharge and the risk of recurrent VTE. The index date was the date of the first apixaban or warfarin claim within 30 days post-discharge. Results: Of the 19,303 eligible patients hospitalized with VTE, 85% (n = 16,401) were treated with apixaban and 15% (n = 2902) received warfarin. After discharge, approximately 70% had ≥1 fill for their respective apixaban or warfarin therapy. The cumulative incidence of discontinuation over the 6 months following index was 50.5% and 52.2% for the apixaban and warfarin cohorts, respectively; the cumulative incidence of switching was 6.0% and 20.9%, respectively. The incidence rates of recurrent VTE were 1.2 and 2.5 per 100 person-years for the apixaban and warfarin cohorts, respectively. Conclusions: The majority of patients continued their apixaban or warfarin therapy following hospital discharge; however, a considerable proportion either switched or discontinued OAC upon transitioning from inpatient care. Among those who continued therapy, discontinuation, switch, and recurrent VTE occurred less often with apixaban vs. warfarin.
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BACKGROUND: Venous thromboembolism (VTE) is a major public health condition that renders patients at risk of recurrent events, which significantly increases their morbidity, mortality, and health care costs. Apart from warfarin, direct oral anticoagulants, such as apixaban, dabigatran, or rivaroxaban, are approved for VTE treatment. Cardiovascular drugs are largely impacted by formulary restrictions; however, the impact on oral anticoagulants (including warfarin and direct oral anticoagulants) in VTE has not been well studied. OBJECTIVE: To describe the extent of payer-rejected claims for oral anticoagulants for VTE and the factors associated with rejected claims. Prescription abandonment of oral anticoagulants and the time to an eventual fill for oral anticoagulant after rejection or abandonment were also evaluated. METHODS: A retrospective cohort study was conducted among patients with VTE newly prescribed an oral anticoagulant (first claim was the index) between October 2016 and October 2021. Descriptive statistics were used to describe the proportion of patients with paid (ie, filled), rejected, or abandoned index oral anticoagulant prescription and journey to paid prescription among those with initial rejection. Multivariable logistic regression was used to identify factors associated with initial rejection. RESULTS: Among the overall sample (N = 297,312), 74.3% had initial oral anticoagulant prescriptions approved, 9.1% had them rejected, and 16.7% abandoned them. Of the patients with initial rejection, 82.1% eventually filled their oral anticoagulant prescriptions; however, for 14.2% of these patients, the first fill was for an oral anticoagulant other than that initially prescribed. The mean time to a first fill for an oral anticoagulant after an initial rejection was 18.3 days. More than half of the patients with an initial rejected oral anticoagulant claim had at least 1 additional rejection during the follow-up period. Of the patients who abandoned their initial oral anticoagulant prescription, 83.9% filled an oral anticoagulant prescription during follow-up; the mean time to fill for the index oral anticoagulant was 15.6 days. Oral anticoagulant type, Medicare payer coverage, prescribing physician specialty, and VTE diagnosis setting of care were significantly associated with index oral anticoagulant claim rejection (P < 0.05). CONCLUSIONS: Rejection and abandonment may delay access to oral anticoagulant treatment. Factors contributing to these scenarios should be understood and addressed for proper VTE management.
Assuntos
Anticoagulantes , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/economia , Estudos Retrospectivos , Feminino , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Anticoagulantes/economia , Masculino , Administração Oral , Pessoa de Meia-Idade , Idoso , Adulto , Prescrições de Medicamentos/estatística & dados numéricos , Estudos de Coortes , Idoso de 80 Anos ou mais , Estados UnidosRESUMO
PURPOSE: Oral anticoagulants effectively prevent stroke/systemic embolism among patients with non-valvular atrial fibrillation but remain under-prescribed. This study evaluated temporal trends in oral anticoagulant use, the incidence of stroke/systemic embolism and major bleeding, and economic outcomes among elderly patients with non-valvular atrial fibrillation and CHA2DS2-VASc scores ≥ 2. METHODS: Retrospective analyses were conducted on Medicare claims data from January 1, 2012 through December 31, 2017. Non-valvular atrial fibrillation patients aged ≥ 65 years with CHA2DS2-VASc scores ≥ 2 were stratified by calendar year (2013-2016) of care to create calendar-year cohorts. Patient characteristics were evaluated across all cohorts during the baseline period (12 months before diagnosis). Treatment patterns and clinical and economic outcomes were evaluated during the follow-up period (from diagnosis through 12 months). RESULTS: Baseline patient characteristics remained generally similar between 2013 and 2016. Although lack of oral anticoagulant prescriptions among eligible patients remained relatively high, utilization did increase progressively (53-58%). Among treated patients, there was a progressive decrease in warfarin use (79-52%) and a progressive increase in overall direct oral anticoagulant use (21-48%). There were progressive decreases in the incidence of stroke/systemic embolism 1.9-1.4 events per 100 person years) and major bleeding (4.6-3.3 events per 100 person years) as well as all-cause costs between 2013 and 2016. CONCLUSIONS: The proportions of patients with non-valvular atrial fibrillation who were not prescribed an oral anticoagulant decreased but remained high. We observed an increase in direct oral anticoagulant use that coincided with decreased incidence of clinical outcomes as well as decreasing total healthcare costs.
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Fibrilação Atrial , Embolia , Acidente Vascular Cerebral , Idoso , Humanos , Estados Unidos/epidemiologia , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/diagnóstico , Medicare , Estudos Retrospectivos , Anticoagulantes/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Hemorragia/tratamento farmacológico , Embolia/prevenção & controle , Custos de Cuidados de Saúde , Administração OralRESUMO
BACKGROUND: Nonadherence to oral anticoagulants (OACs) is a challenge to stroke risk reduction in patients with nonvalvular atrial fibrillation (NVAF). Data on primary medication nonadherence (PMN) in NVAF are lacking. OBJECTIVES: Our aim was to assess the rates and predictors of PMN among NVAF patients who were newly prescribed an OAC. METHODS: This was a retrospective database analysis of linked healthcare claims and electronic health record data. Adult NVAF patients with a prescription order for an OAC (apixaban, rivaroxaban, dabigatran, or warfarin) between January 2016 and June 2019 were identified (date of first prescription order = index date). Patients had a 1-year baseline and a 6-month post-index period to assess the rates of PMN, defined as having a prescription order but no paid claim for any OAC on or within 30 days after the index date. Sensitivity analyses explored 60-, 90- and 180-day PMN thresholds. Logistic regression models were used to examine the predictors of PMN. RESULTS: Among 20,393 patients, the overall 30-day PMN rate was 28.4%; PMN rates decreased to 17% with a 180-day threshold. PMN was numerically lowest for warfarin among OACs and numerically lowest for apixaban among direct OACs. A CHA2DS2-VASc score of ≥ 3, commercial insurance, and African American race were associated with higher odds of PMN. CONCLUSIONS: More than one-quarter of patients experienced PMN within 30 days of their initial prescription order. This rate decreased over a longer period, suggesting a delay in fills. Understanding the factors associated with PMN is warranted to develop effective interventions for improving OAC treatment rates in NVAF.
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Fibrilação Atrial , Acidente Vascular Cerebral , Adulto , Humanos , Estados Unidos/epidemiologia , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Varfarina/uso terapêutico , Estudos Retrospectivos , Anticoagulantes/uso terapêutico , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Dabigatrana/uso terapêutico , Adesão à Medicação , Administração OralRESUMO
BACKGROUND: Atrial fibrillation (AF) prevalence estimates vary and have been based on cohorts with clinically established or diagnosed disease. Undiagnosed AF prevalence estimates are less certain as they are based on nongeneralizable convenience samples. HYPOTHESIS: Because AF is often asymptomatic, it my remain undiagnosed until the development of complications such as stroke or heart failure. Consequently, the observed prevalence of diagnosed AF from the literature may underestimate total disease burden. We therefore sought to estimate the total prevalence of both diagnosed and undiagnosed AF. METHODS: We performed a retrospective cohort study from 2012 to 2017 using data from five US medical claims data sets. Undiagnosed AF prevalence was estimated based on the observed incidence of ischemic stroke, systemic embolism (SE), and AF incidence after a stroke/SE. The diagnosed AF cohort included AF patients between Q1 2014 and Q3 2015. The undiagnosed AF cohort were patients with assumed undiagnosed AF in the year before a stroke/SE and who were newly diagnosed with AF in the 3-month poststroke/SE. Stroke/SE incidence was calculated among all AF patients and the ratio of number of undiagnosed AF patients to stroke rate was created. Age- and sex-adjusted estimates were stratified by period of assumed undiagnosed AF before poststroke/SE AF diagnosis (1 or 2 years). RESULTS: The estimated US prevalence of AF (diagnosed and undiagnosed) in Q3 2015 was 5 628 000 cases, of which 591 000 cases (11%) were undiagnosed. The assumed 2-year undiagnosed AF prevalence was 23% (1 531 000) of the total prevalent patients with AF (6 568 000). Undiagnosed (vs. diagnosed) AF patients were older and had higher CHA2DS2-VASc scores. Of undiagnosed AF, 93% had CHA2DS2-VASc ≥2 and met OAC criteria. CONCLUSIONS: These contemporary estimates demonstrate the high prevalence of undiagnosed AF in the United States. Undiagnosed AF patients are composed of primarily elderly individuals who if diagnosed, would meet criteria for stroke prevention therapy.
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Fibrilação Atrial , Acidente Vascular Cerebral , Humanos , Estados Unidos/epidemiologia , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/complicações , Estudos Retrospectivos , Medição de Risco , Prevalência , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Anticoagulantes , Fatores de RiscoRESUMO
The evidence of direct oral anticoagulants (DOACs) usage for venous thromboembolism (VTE) in patients at extremes of body weight or mass index is limited. In such situations, warfarin may be more frequently used. We investigated warfarin time in the therapeutic international normalized ratio range (TTR) and DOAC adherence based on the calculated proportion of days covered (PDC) by pill coverage from a DOAC prescription in patients with VTE across all body sizes. Using data from the Veterans Health Administration (VA), we identified first-time patients with VTE between 2013 and 2018 treated with warfarin or DOACs. We analyzed 28,245 patients with warfarin TTR (N = 10,167) or DOAC PDC(N = 18,078). For warfarin-treated patients after index VTE, mean TTR was lower over shorter treatment durations (TTR 30 vs TTR 180 [mean ± SD]: 43.8% ± 33.5% vs 58.8% ± 23.5%). Mean TTR over 180 days after VTE was lowest for patients <60â kg (TTR 180 [mean ± SD]: <60kg: 49.3% ± 24.2% vs ≥60 to <100â kg: 57.8% ± 23.4%; P < .0001). For DOAC-treated patients over 180 days after index VTE, mean PDC was lowest for patients <60â kg (PDC 180 [mean ± SD]: < 60kg: 76.9% ± 33.2% vs ≥ 60 to <100â kg: 83.6% ± 27.7%; P < .0001).Most DOAC-treated patients attained sufficient adherence across the body size spectrum while warfarin-treated patients <60kg were at risk for low TTR.
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Tromboembolia Venosa , Varfarina , Humanos , Varfarina/farmacologia , Varfarina/uso terapêutico , Anticoagulantes , Coeficiente Internacional Normatizado , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/induzido quimicamente , Índice de Massa Corporal , Saúde dos Veteranos , Estudos Retrospectivos , Administração OralRESUMO
INTRODUCTION: In the USA, there is a steady rise of atrial fibrillation due to the aging population with increased morbidity. This study evaluated the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) among elderly patients with non-valvular atrial fibrillation (NVAF) and multimorbidity prescribed direct oral anticoagulants (DOACs). METHODS: Using the CMS Medicare database, a retrospective observational study of adult patients with NVAF and multimorbidity who initiated apixaban, dabigatran, or rivaroxaban from January 1, 2012 to December 31, 2017 was conducted. High multimorbidity was classified as having ≥ 6 comorbidities. Cox proportional hazard models were used to evaluate the hazard ratios of S/SE and MB among three 1:1 propensity score matched DOAC cohorts. All-cause healthcare costs were estimated using generalized linear models. RESULTS: Overall 36% of the NVAF study population had high multimorbidity, forming three propensity score matched (PSM) cohorts: 12,511 apixaban-dabigatran, 60,287 apixaban-rivaroxaban, and 12,567 dabigatran-rivaroxaban patients. Apixaban was associated with a lower risk of stroke/SE and MB when compared with dabigatran and rivaroxaban. Dabigatran had a lower risk of stroke/SE and a similar risk of MB when compared with rivaroxaban. Compared to rivaroxaban, apixaban patients incurred lower all-cause healthcare costs, and dabigatran patients incurred similar all-cause healthcare costs. Compared to dabigatran, apixaban patients incurred similar all-cause healthcare costs. CONCLUSION: Patients with NVAF and ≥ 6 comorbid conditions had significantly different risks for stroke/SE and MB when comparing DOACs to DOACs, and different healthcare expenses. This study's results may be useful for evaluating the risk-benefit ratio of DOAC use in patients with NVAF and multimorbidity.
Assuntos
Fibrilação Atrial , Embolia , Acidente Vascular Cerebral , Adulto , Humanos , Idoso , Estados Unidos/epidemiologia , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Rivaroxabana/efeitos adversos , Varfarina/uso terapêutico , Anticoagulantes/efeitos adversos , Dabigatrana/efeitos adversos , Multimorbidade , Medicare , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Medição de Risco , Piridonas/efeitos adversos , Administração OralRESUMO
BACKGROUND: Oral anticoagulants (OACs) mitigate stroke risk in patients with atrial fibrillation (AF). The study aim was to analyze prevalence and predictors of OAC underutilization. METHODS: Newly diagnosed AF patients with a CHA2DS2-VASc score ≥ 2 were identified from the US CMS Database (January 1, 2013-December 31, 2017). Patients were stratified based on having an OAC prescription versus not and the OAC prescription group was stratified by direct OAC (DOACs) versus warfarin. Multivariable logistic regression models were used to examine predictors of OAC underutilization. RESULTS: Among 1,204,507 identified AF patients, 617,611 patients (51.3%) were not prescribed an OAC during follow-up (mean: 2.4 years), and 586,896 patients (48.7%) were prescribed an OAC during this period (DOAC: 388,629 [66.2%]; warfarin: 198,267 [33.8%]). Age ≥ 85 years (odds ratio [OR] 0.55, 95% confidence interval [CI] 0.55-0.56), female sex (OR 0.96, 95% CI 0.95-0.96), Black race (OR 0.78, 95% CI 0.77-0.79) and comorbidities such as gastrointestinal (GI; OR 0.43, 95% CI 0.41-0.44) and intracranial bleeding (OR 0.29, 95% CI 0.28-0.31) were associated with lower utilization of OACs. Furthermore, age ≥ 85 years (OR 0.92, 95% CI 0.91-0.94), Black race (OR 0.78, 95% CI 0.76-0.80), ischemic stroke (OR 0.77, 95% CI 0.75-0.80), GI bleeding (OR 0.73, 95% CI 0.68-0.77), and intracranial bleeding (OR 0.72, 95% CI 0.65-0.80) predicted lower use of DOACs versus warfarin. CONCLUSIONS: Although OAC therapy prescription is the standard of care for stroke prevention in AF patients, its overall utilization is still low among Medicare patients ≥ 65 years old, with specific patient characteristics that predict underutilization.
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Fibrilação Atrial , Acidente Vascular Cerebral , Humanos , Feminino , Idoso , Estados Unidos/epidemiologia , Idoso de 80 Anos ou mais , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/complicações , Varfarina/uso terapêutico , Medicare , Anticoagulantes/uso terapêutico , Administração Oral , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Estudos RetrospectivosRESUMO
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 1â¯141â¯097 patients with nonvalvular atrial fibrillation; the mean (SD) age was 75.0 (10.5) years, 608â¯127 patients (53.3%) were men, and over 1 million were placed in the 2 highest risk categories (high risk 1, 327â¯766 participants; high risk 2, 688â¯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.
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Fibrilação Atrial , Embolia , Acidente Vascular Cerebral , Tromboembolia , Adulto , Idoso , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Estudos de Coortes , Embolia/epidemiologia , Embolia/etiologia , Embolia/prevenção & controle , Feminino , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Masculino , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Tromboembolia/epidemiologia , Tromboembolia/etiologia , Tromboembolia/prevenção & controleRESUMO
Relatively little is known about the influence of extreme body weight on the pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and safety of drugs used in many disease states. While direct oral anticoagulants (DOACs) have an advantage over warfarin in that they do not require routine drug monitoring, some may regard this convenience as less compelling in obese patients. Some consensus guidelines discourage using DOACs in patients weighing > 120 kg or with a body mass index > 35-40 kg/m2, given a sparsity of available data in this population and the concern that fixed dosing in obese patients might lead to decreased drug exposure and lower efficacy. Per the prescribing information, apixaban does not require dose adjustment in patients weighing above a certain threshold (e.g., ≥ 120 kg). Data from healthy volunteers and patients with nonvalvular atrial fibrillation (NVAF) or venous thromboembolism (VTE) have shown that increased body weight has a modest effect on apixaban's PK. However, the paucity of exposure data in individuals > 120 kg and the lack of guideline consensus on DOAC use in obese patients continue to raise concerns about potential decreased drug exposure at extreme weight. This article is the first to comprehensively review the available PK data in obese individuals without NVAF or VTE, and PK, PD, efficacy, effectiveness, and safety data for apixaban in obese patients with either NVAF or VTE, including subgroup analyses across randomized controlled trials and observational (real-world) studies. These data suggest that obesity does not substantially influence the efficacy, effectiveness, or safety of apixaban in these patients. Trial Registration ARISTOTLE: NCT00412984; AVERROES: NCT00496769; AMPLIFY: NCT00643201; AMPLIFY-EXT: NCT00633893; ADVANCE-1: NCT00371683; ADVANCE-2: NCT00452530; ADVANCE-3: NCT00423319 Apixaban Use in Obese Patients: A Review of the Pharmacokinetic, Interventional, and Observational Study Data (MP4 161.22 MB).
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Fibrilação Atrial , Acidente Vascular Cerebral , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/tratamento farmacológico , Piridonas/efeitos adversos , Varfarina/uso terapêutico , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Obesidade/complicações , Obesidade/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Administração Oral , Estudos Observacionais como AssuntoRESUMO
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.
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Fibrilação Atrial , Acidente Vascular Cerebral , Administração Oral , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Teorema de Bayes , Dabigatrana/uso terapêutico , Fibrinolíticos/uso terapêutico , Humanos , Metanálise em Rede , Piridonas/uso terapêutico , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Vitamina KRESUMO
This study describes demographics, thrombotic and bleeding events, mortality, and anticoagulant use among hospitalized patients with COVID-19 in the United States. Premier Healthcare Database data were analyzed to identify inpatients with a discharge diagnosis for COVID-19 (ICD-10-CM code: U07.1) from April 1, 2020 to March 31, 2021, and matched historical controls without COVID-19 (inpatients discharged between April 1, 2018 and March 31, 2019). Thrombotic [including venous thromboembolism (VTE)] and bleeding events were based on ICD-10-CM discharge diagnosis codes. Of the 546,656 patients hospitalized with COVID-19, 20.1% were admitted to the ICU, 62.8% were aged ≥ 60 years, 51.5% were male, and 31.0% were non-white. Any thrombotic event was diagnosed in 10.0% of hospitalized and 20.8% of ICU patients with COVID-19 versus (vs) 11.5% and 24.4% for historical controls, respectively. More VTE events were observed in hospitalized and ICU patients with COVID-19 than historical controls (hospitalized: 4.4% vs 2.7%, respectively; ICU: 8.3% vs 5.2%, respectively; both P < 0.0001). Bleeding events were diagnosed in 10.2% of hospitalized and 21.8% of ICU patients with COVID-19 vs 16.0% and 33.2% for historical controls, respectively. Mortality among hospitalized (12.4%) and ICU (38.5%) patients with COVID-19 was higher vs historical controls (2.4%, P < 0.0001 and 9.4%, P < 0.0001, respectively) and higher in hospitalized patients with COVID-19 who had thrombotic events (29.4%) vs those without thrombotic events (10.8%, P < 0.0001). VTE and mortality were higher in hospitalized and ICU patients with COVID-19 vs historical controls. The presence of thrombotic events was associated with worse outcomes.
Assuntos
COVID-19 , Trombose , Tromboembolia Venosa , Anticoagulantes/efeitos adversos , COVID-19/complicações , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Estudos Retrospectivos , Trombose/induzido quimicamente , Estados Unidos/epidemiologia , Tromboembolia Venosa/induzido quimicamente , Tromboembolia Venosa/epidemiologiaRESUMO
BACKGROUND: Oral anticoagulants (OACs) mitigate the risk of stroke in atrial fibrillation (AF) patients. OBJECTIVE: Elderly AF patients who were treated with OACs (apixaban, dabigatran, edoxaban, rivaroxaban, or warfarin) were compared against AF patients who were not treated with OACs with respect to their clinical and economic outcomes. METHODS: Newly diagnosed AF patients were identified between January 2013 and December 2017 in the Medicare database. Evidence of an OAC treatment claim on or after the first AF diagnosis was used to classify patients into treatment-defined cohorts, and these cohorts were further stratified based on the initial OAC prescribed. The risks of stroke/systemic embolism (SE), major bleeding (MB), and death were analyzed using inverse probability treatment weighted time-dependent Cox regression models, and costs were compared with marginal structural models. RESULTS: The two treatment groups were composed of 1,421,187 AF patients: OAC treated (N = 583,350, 41.0% [36.4% apixaban, 4.9% dabigatran, 0.1% edoxaban, 26.7% rivaroxaban, and 31.9% warfarin patients]) and untreated (N = 837,837, 59.0%). OAC-treated patients had a lower adjusted risk of stroke/SE compared to untreated patients (hazard ratio [HR]: 0.70; 95% confidence interval [CI]: 0.68-0.72). Additionally patients receiving OACs had a lower adjusted risk of death (HR: 0.56; 95% CI: 0.55-0.56) and a higher risk of MB (HR: 1.57; 95% CI: 1.54-1.59) and this trend was consistent across each OAC sub-group. The OAC-treated cohort had lower adjusted total healthcare costs per patient per month ($4,381 vs $7,172; p < .0001). CONCLUSION: For the OAC-treated cohort in this elderly US population, stroke/SE and all-cause death were lower, while risk of MB was higher. Among OAC treated patients, total healthcare costs were lower than those of the untreated cohort.
Assuntos
Anticoagulantes/economia , Fibrilação Atrial/economia , Bases de Dados Factuais/estatística & dados numéricos , Custos de Cuidados de Saúde/estatística & dados numéricos , Hemorragia/epidemiologia , Acidente Vascular Cerebral/economia , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/patologia , Estudos de Casos e Controles , Feminino , Seguimentos , Hemorragia/economia , Humanos , Masculino , Medicare , Prognóstico , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Taxa de Sobrevida , Estados Unidos/epidemiologiaRESUMO
Real-world studies have evaluated the use of anticoagulants in obese patients with nonvalvular atrial fibrillation (NVAF), but they have been limited by sample size or the use of diagnosis codes on claims to define obesity. This retrospective study used body weight data of ≥100 kg or a body mass index of ≥30 kg/m2 to identify elderly (aged ≥65 years) NVAF patients with obesity in dually enrolled Veterans Affairs and fee-for-service Medicare patients. It evaluated the risk of stroke/systemic embolism (SE) and major bleeding (MB) in patients that initiated apixaban versus warfarin. Stabilized inverse probability treatment weighting was used to balance the baseline characteristics between patients prescribed apixaban and warfarin in obese patients. Cox models were used to evaluate the relative risk of stroke/SE and MB. Overall, 35.9% (nâ¯=â¯26,522) of the NVAF population were obese, of which 13,604 apixaban and 12,918 warfarin patients were included. After inverse probability treatment weighting, patient characteristics were balanced. The mean age was 75 years, the mean CHA2DS2-VASc score (Congestive Heart Failure, Hypertension, Age ≥75 [Doubled], Diabetes Mellitus, Prior Stroke or Transient Ischemic Attack [Doubled], Vascular Disease, Age 65-74, Female) was 3.8, the mean HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) Score was â¼2.6, and >98% of patients were males. Obese apixaban patients were associated with a similar risk of stroke/SE (hazard ratio: 0.82; 95% confidence interval: 0.66 to 1.03) and a significantly lower risk of MB (hazard ratio: 0.62; 95% confidence interval: 0.54 to 0.70) versus warfarin. No significant interaction was observed between treatment and obesity status (nonobese, obese/nonmorbid, obese/morbid) for stroke/SE (interaction pâ¯=â¯0.602) or MB (interaction pâ¯=â¯0.385). In obese patients with NVAF, apixaban was associated with a similar risk of stroke/SE and a significantly lower risk of MB versus warfarin.
Assuntos
Fibrilação Atrial/tratamento farmacológico , Inibidores do Fator Xa/uso terapêutico , Obesidade/complicações , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Varfarina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Medicare , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Modelos de Riscos Proporcionais , Acidente Vascular Cerebral/etiologia , Resultado do Tratamento , Estados Unidos , United States Department of Veterans AffairsRESUMO
BACKGROUND: Studies have shown that patients with non-valvular atrial fibrillation (NVAF) who discontinue oral anticoagulants (OACs) are at higher risk of complications such as stroke. OBJECTIVE: This analysis compared the risk of non-persistence with OACs among patients with NVAF. METHODS: Adult patients with NVAF who initiated apixaban, dabigatran, rivaroxaban, or warfarin were identified using 01JAN2013-30JUN2019 data from Centers for Medicare and Medicaid Services and four US commercial claims databases. Non-persistence was defined as discontinuation (no evidence of index OAC use for ≥ 60 days from the last days' supply) or switch to another OAC. Kaplan-Meier curves were generated to illustrate time to non-persistence along with cumulative incidences of non-persistence. Baseline and time-varying covariates were evaluated, and adjusted Cox proportional hazards models were used to evaluate non-persistence risk. RESULTS: In total, 363,823 patients receiving apixaban, 57,121 receiving dabigatran, 282,831 receiving rivaroxaban, and 317,337 receiving warfarin were included. Of these, 47-72% discontinued/switched OAC therapy within an average 9-month follow-up. Apixaban was associated with a lower risk of non-persistence than were dabigatran (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.61-0.62), rivaroxaban (HR 0.76; 95% CI 0.75-0.76), and warfarin (HR 0.74; 95% CI 0.74-0.75). Dabigatran was associated with a higher risk of non-persistence than were warfarin (HR 1.21; 95% CI 1.19-1.22) and rivaroxaban (HR 1.23; 95% CI 1.22-1.25), and rivaroxaban was associated with a lower risk of non-persistence than was warfarin (HR 0.98; 95% CI 0.97-0.98). Clinical events (stroke/systemic embolism and major bleeding [MB]) during follow-up were predictors of non-persistence (stroke HR 1.57; 95% CI 1.53-1.61; MB HR 2.96; 95% CI 2.92-3.00). CONCLUSION: In over one million patients with NVAF, our results suggest differences in anticoagulation treatment persistence across OAC agents, even after accounting for clinical events after OAC initiation. It is important for clinicians and patients to take these differences into consideration, especially as non-persistence to OAC therapy is associated with thromboembolic complications.
Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Administração Oral , Adulto , Idoso , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Dabigatrana/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Hemorragia/epidemiologia , Humanos , Medicare , Piridonas/efeitos adversos , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Estados Unidos/epidemiologia , Varfarina/efeitos adversosRESUMO
BACKGROUND: Consensus statements have recommended against the use of direct oral anticoagulants (DOACs) in venous thromboembolism (VTE) for patients ≥120 kg and ≥40 kg/m2. We sought to determine use and outcomes of DOACs for VTE across weight and body mass index (BMI). METHODS: We performed a retrospective cohort study of patients with first-time VTE 2013 to 2018 that were treated with DOAC or warfarin in the Veterans Health Administration. The Veterans Health Administration has implemented system-wide guidance for patient selection and shared decision-making for use of DOACs in VTE at extremes of weight. We stratified patients by weight and BMI and assessed (1) association of weight and BMI category to outcomes in those prescribed DOAC; and (2) association of DOAC, as compared to warfarin, to outcomes by weight and BMI categories. Outcomes of interest included major bleeding, clinically relevant nonmajor bleeding, and recurrent VTE. RESULTS: The analysis cohort included 51 871 patients prescribed DOAC or warfarin within 30 days of index VTE diagnosis (age 64.5±13.1 years; 6.0% female; median weight 93.4 kg [25th-75th: 80.5-108.6 kg]). For patients ≥120 kg (N=6934 patients), 38.4% were treated with DOAC, as compared to 45.4% of those ≥60 to <100 kg (N=30 645; P<0.0001). DOAC prescription was not associated with major bleeds, clinically relevant nonmajor bleeds, or recurrent VTE for those in higher weight and BMI categories as compared to those in average weight and BMI categories. DOAC prescription, as compared to warfarin, was not associated with increased recurrent VTE in any weight or BMI category. CONCLUSIONS: Patients ≥120 kg and ≥40 kg/m2 with VTE are frequently prescribed DOAC by the Veterans Health Administration, without an increase in bleeding or recurrent VTE. These findings suggest DOACs can be safe and effective in this population and may argue for broader adoption of pharmacy policies that promote careful patient selection and shared decision making.
Assuntos
Tromboembolia Venosa , Administração Oral , Idoso , Anticoagulantes/efeitos adversos , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/epidemiologia , Saúde dos VeteranosRESUMO
BACKGROUND AND AIMS: Analysed using classical frequentist hypothesis testing with alpha set to 0.05, the Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES) did not find enough evidence to reject the hypothesis of no difference in neuropsychiatric adverse events (NPSAEs) attributable to varenicline, bupropion, or nicotine patch compared with placebo. This might be because the null hypothesis was true or because the data were insensitive. The present study aimed to test the hypothesis more directly using Bayes factors. DESIGN: EAGLES was a randomised, double-blind, triple-dummy, controlled trial. SETTING: Global (16 countries across five continents), between November 2011 and January 2015. PARTICIPANTS: Participants were smokers with (n = 4116) and without (n = 4028) psychiatric disorders. INTERVENTIONS: Varenicline (1 mg twice daily), bupropion (150 mg twice daily), nicotine patch (21 mg once daily with taper) and matched placebos. MEASUREMENTS: The outcomes included: (i) a composite measure of moderate/severe NPSAEs; and (ii) a composite measure of severe NPSAEs. The relative evidence for there being no difference in NPSAEs versus data insensitivity for the medications was calculated in the full and sub-samples using Bayes factors and corresponding robustness regions. FINDINGS: For all but two comparisons, Bayes factors were <1/3, indicating moderate to strong evidence for no difference in risk of NPSAEs between active medications and placebo (Bayes factor = 0.02-0.23). In the psychiatric cohort versus placebo, the data were suggestive, but not conclusive of no increase in NPSAEs with varenicline (Bayes factor = 0.52) and bupropion (Bayes factor = 0.71). Here, the robustness regions ruled out a ≥7% and ≥8% risk increase with varenicline and bupropion, respectively. CONCLUSIONS: Secondary analysis of the Evaluating Adverse Events in a Global Smoking Cessation Study trial using Bayes factors provides moderate to strong evidence that use of varenicline, bupropion or nicotine patches for smoking cessation does not increase the risk of neuropsychiatric adverse events relative to use of placebo in smokers without a history of psychiatric disorder. For smokers with a history of psychiatric disorder the evidence also points to no increased risk but with less confidence.