Non-vitamin K Antagonist Oral Anticoagulants Prescriptions Research Articles

Delayed Prescribing of Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) in Patients with Low Socioeconomic Status

Background/Objective: Atrial fibrillation (AF) and venous thromboembolism (VTE) are conditions with significant morbidity and mortality when left untreated. American Heart Association guidelines changed in 2019 to make non-vitamin K antagonist oral anticoagulants (NOACs) the preferred method for preventing stroke and systemic embolism in patients with AF or history of VTE. NOACs were first introduced to the United States in 2010 and now include dabigatran, apixaban, rivaroxaban, and edoxaban. There is a dearth of research concerning the speed with which new treatments are prescribed to those in different socioeconomic status (SES) groups. We hypothesized that patients with lower SES were prescribed NOACs later than higher SES counterparts following the introduction of NOACs in 2010.
 Methods: The IU Cardiovascular Research Consortium/Sidus Dataset was mined for AF and VTE patients prescribed a NOAC between 2010 and 2022. The SES groups were determined using 2020 U.S. Census income data that correlated to patients’ zip codes. The yearly number ofpatients in each SES group were compared to assess for proportional uptake of NOAC prescribing. The primary outcome was the proportion of low SES to high SES prescribing over each year between 2010 and 2022.
 Results: Low SES patients (n=101,945) were prescribed NOACs at an average of 0.65 times the rate of high SES patients (n= 89,130) from 2010 to 2012, the first three years of NOAC market availability. Prescribing rates equilibrated in 2013 and low SES prescribing has outpaced high SES prescribing since 2021.
 Conclusion/Impact: Low SES patients experienced a three year delay in receiving NOAC prescriptions at the same rate as their high SES counterparts. Systemic changes, like more frequent prescribing guideline updates and improved evidence-based education amongst providers in low-income areas, could prevent a similar delay when introducing similarly transformative treatments in the future.

Survey of Using Oral Anticoagulants in Patient with Non-valvular Atrial Fibrillation.

In Vietnam, there has been no survey conducted on the prescribing and monitoring practices of oral anticoagulants to ensure that patients with atrial fibrillation receive appropriate. Objective: Therefore, we conducted this research to clarify the aforementioned issue in our hospital. We carried out a cross-sectional study by reviewing outpatient electronic medical records at the University Medical Center in Ho Chi Minh City. Our study included 1087 patients aged 18 years or older diagnosed with non-valvular atrial fibrillation (NVAF), who visited the Cardiology clinic between January 1st, 2021, and June 30th, 2021. Among the 1087 patients with non-valvular atrial fibrillation (NVAF), 1036 were eligible for anticoagulant therapy. However, only 847 (81.8%) received prescriptions for either Vitamin K antagonists (VKAs) (n=129, 15.2%) or Non-Vitamin K antagonist oral anticoagulants (NOACs) (n=718, 84.8%). NOAC prescriptions were more commonly found in patients aged 75 or older (adjusted odds ratio [OR]=2), those with health insurance coverage (adjusted OR=2.9), and in individuals with a history of hypertension (adjusted OR=2). On the contrary, patients with a farming occupation were less likely to be prescribed NOACs (adjusted OR=0.4). About 75% of patients adhered to the guidelines recommending close monitoring during anticoagulant treatment. Notably, inappropriate prescriptions were identified in 27.7% of cases, especially among those with no recorded body weight (which is necessary for precise dosing based on creatinine clearance), those without health insurance, those with undocumented CHA2DS2-VASc scores, or those who were concurrently using antiplatelet agents. A discrepancy persists between clinical guidelines and the actual practice in diagnosing and managing patients with non-valvular atrial fibrillation (NVAF). It is crucial to prioritize the regular reevaluation of thromboembolic risk scores at follow-up appointments, ensure strict adherence to clinical monitoring standards, and align anticoagulant medication prescriptions with established guidelines.

Optimal adherence threshold to non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation to reduce the risk of thromboembolism and death

Abstract Background Poor adherence to non-vitamin K antagonist oral anticoagulants (NOACs) may raise thromboembolic risks in patients with atrial fibrillation (AF). However, the minimal adherence to maintain the protective effects of NOACs is currently unknown. Purpose To investigate thresholds of NOAC adherence in association with thromboembolic and mortality risks. Methods Using two Belgian nationwide healthcare databases, AF patients ≥45 years old with ≥1 NOAC prescription claim between January 1st, 2013 and January 1st, 2019 were identified. Patients were followed from NOAC initiation until the first occurrence of the investigated outcome, treatment discontinuation (>60-day supply gap), switch to VKAs, death, emigration or end of the study period. Adherence was measured using the proportion of days covered (PDC) after one year of treatment. Inverse probability weighted Cox regression (adjusting for 39 confounding covariates) was used to investigate outcomes (identified using International Classification of Diseases-coded hospital discharge diagnoses and medical procedure codes) between NOAC users with a one-year PDC of 100% (reference group) and NOAC users with lower PDCs. Results A total of 92,111 newly-treated AF patients were included during a mean follow-up of 2.7 ± 1.4 years (250,750 person-years of on-treatment follow-up). The proportions of persistent NOAC users with a PDC of 100%, 95-99%, 90-94%, 85-89%, 80-84% and <80% after one year of treatment were 62.7%, 17.4%, 9.5%, 5.1%, 2.8% and 2.5%, respectively. Compared to NOAC users with a one-year PDC of 100%, significantly higher risks of stroke or systemic embolism were observed among NOAC users with PDCs of 85-89% (adjusted hazard ratio (aHR) 1.35, 95% confidence interval (CI) (1.19-1.54)), 80-84% (aHR 1.31, 95%CI (1.08-1.58)) and <80% (aHR 1.64, 95%CI (1.34-2.01)), while no significant differences were observed among NOAC users with one-year PDCs of 95-99% (aHR 1.02, 95%CI (0.94-1.12)) or 90-94% (aHR 1.06, 95%CI (0.95-1.18)) after multivariable adjustment. Significantly higher risks of all-cause mortality (aHR 1.09, 95%CI (1.01-1.17) and major or clinically relevant non-major bleeding (aHR 1.10, 95%CI (1.04-1.16) were observed with decreasing levels of NOAC adherence, starting from NOAC users with a one-year PDC of 90-94% versus 100%. Findings were similar with once-daily and twice-daily dosed NOACs. Conclusion Lower adherence to NOAC treatment is associated with increased risks of thromboembolism, all-cause mortality and bleeding. For adequate stroke prevention in AF, the optimal adherence threshold to NOAC treatment should be at least 90%, irrespective of the dosing regimen of NOACs.Figure 1

Contemporary management of atrial fibrillation in primary and secondary care in the UK: the prospective long-term AF-GEN-UK Registry.

This study established a prospective registry of contemporary management of UK patients with atrial fibrillation (AF) by cardiologists, general practitioners, and stroke, acute, and emergency medicine physicians at baseline and 1-year follow-up. Data on patients with recently diagnosed AF (≤12 months) were collected from medical records from 101 UK sites to permit comparison of patient characteristics and treatments between specialities. The impact of guideline-adherent oral anticoagulation (OAC) use on outcomes was assessed using Cox regression analysis. One thousand five hundred and ninety-five AF patients [mean (standard deviation) age 70.5 (11.2) years; 60.1% male; 97.4% white] were recruited in June 2017-June 2018 and followed up for 1 year. Overall OAC prescription rates were 84.2% at baseline and 87.1% at 1 year, with non-vitamin K antagonist oral anticoagulants (NOACs) predominating (74.9 and 79.2% at baseline and 1 year, respectively). Vitamin K antagonist prescription was significantly higher in primary care, with NOAC prescription higher among stroke physicians. Guideline-adherent OAC (CHA2DS2-VASc ≥2) at baseline significantly reduced risk of death and stroke at 1 year [adjusted hazard ratio (95% confidence interval): 0.48 (0.27-0.84) and 0.11 (0.02-0.48), respectively]. Rhythm control is evident in ∼25%; only 1.6% received catheter ablation. High OAC use (>80%, mainly NOACs) rates varied by speciality, with VKA prescription higher in primary care. Guideline-adherent OAC therapy at baseline was associated with significant reduction in death and stroke at 1 year, regardless of speciality. Rhythm-control management is evident in only one-quarter despite AF symptoms reported in 56.6%. This registry extends the knowledge of contemporary AF management outside cardiology and demonstrates good implementation of clinical guidelines for the management of AF, particularly for stroke prevention.

Bleeding risk in patients with atrial fibrillation treated with combined anti-platelet and non-vitamin K antagonist oral anticoagulant therapy.

The use of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with non-valvular atrial fibrillation (AF) has been increasing. Accordingly, the combined use of antiplatelet agents (APT) and NOAC therapy is commonly encountered in clinical practice. The purpose of this study was to compare the clinical outcomes between combination therapy (NOAC and APT) vs. monotherapy (NOAC only) in patients with AF. We retrospectively analyzed patients who were prescribed NOACs between January 2012 and December 2016. The primary outcome was major bleeding and any bleeding events, and the secondary outcomes were stroke/systemic embolic (SE) events and major adverse cardiac events (MACE). Of the 1068 participants, there were 264 (24.7%) patients in the combination therapy group. The prevalence of diabetes (p = 0.017) and history of stroke and transient ischemic attacks (p < 0.001) was higher in the combination group than in the monotherapy group. During the mean 14.6 ± 9.8 months of follow-up, the incidence of any bleeding was significantly higher in the combination therapy group than in the monotherapy group (p < 0.001). The rate of major bleeding, stroke/SE, and MACE between the two groups was similar. The rate of under-dosage NOAC prescriptions was higher in the combination therapy group than in the monotherapy group (p = 0.024). The combination therapy group had higher incidences of any bleeding events compared to the monotherapy in patients with appropriate dosing. However, there was no difference in stroke/SE, and MACE. The bleeding risk in AF patients taking the combination of NOACs and APT should be carefully evaluated.

Time at home among nonvalvular atrial fibrillation patients treated with non-vitamin K antagonist oral anticoagulants: an ARISTOPHANES analysis

Abstract Background Patient-centered outcomes, such as home time, are becoming increasingly important quality-of-life measures. There are limited data on the impact of oral anticoagulants (OACs) on home time among patients with non-valvular atrial fibrillation. Purpose This analysis, based on the previously published ARISTOPHANES study, used five US insurance claims databases (CMS Medicare and four commercial databases) to compare home time among NVAF patients who were prescribed non-vitamin K antagonist OACs (NOACs). Methods Adult NVAF patients who were newly prescribed apixaban, dabigatran, or rivaroxaban (01JAN2013–30SEP2015) were selected. Time at home was calculated as the number of days from the index date (NOAC prescription) without any of the following: an inpatient, skilled nursing facility (SNF) or nursing facility, hospice, or inpatient rehabilitation facility admission. Time at home and without external AF-related care was defined as days from index date without any events from the home time endpoint or any days with a claim for bleeding, stroke/systemic embolism (S/SE), AF, or an INR test. Time at home and without external AF-related care were measured during the 180 days of follow-up; patients were required to have been alive and have 180 days of follow-up post index. In each database, three 1:1 NOAC-NOAC propensity-score-matched (PSM) cohorts were created before combining the databases. For each NOAC-NOAC matched cohort, Poisson regression was conducted to compare time at home and time at home without external AF-related care. Results After PSM, 37,314 apixaban-dabigatran, 107,236 apixaban-rivaroxaban, and 37,693 rivaroxaban-dabigatran patient pairs were created of which 37–44% had 180 days of follow-up available. Across the NOAC cohorts, approximately 21–25% of patients had an admission to a hospital, SNF, nursing facility, rehabilitation center, or hospice during the 180-day follow-up. The time at home was generally consistent between the NOAC cohorts (177 days); however, apixaban patients had 0.5 more days at home compared to rivaroxaban patients. Across all NOAC cohorts, 7–8% had a claim for a S/SE, 11–15% had a claim for bleeding, and 15–22% had an INR test, while 87–89% of all patients had an AF-claim during the 180-day follow-up. Patients prescribed apixaban had 1 more day at home without external AF-related care compared to dabigatran, and 1.5 more days at home without external AF-related care compared to rivaroxaban. Dabigatran had &amp;lt;1 more day at home without external AF-related care compared to rivaroxaban. Conclusion Among NVAF patients treated with NOACs, there were small differences in the time at home and time at home without external AF-related care during the first 6 months of NOAC treatment. As NVAF is a chronic condition, it is important to understand the impact of NOAC treatment on these patient-centered outcomes. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bristol-Myers Squibb Company and Pfizer Inc.

Bleeding risk in patients with atrial fibrillation treated with combined anti-platelet and NOAC therapy

Abstract Background The combined use of antiplatelet agents (APT) and non-vitamin K antagonist oral anticoagulants (NOACs) in patient with atrial fibrillation (AF) is commonly encountered in clinical practice. The purpose of this study was to compare the clinical outcomes between combination therapy (NOAC and APT) and monotherapy (NOAC only). Methods and results We analyzed patients who were prescribed NOACs between January 2012 and December 2016. The primary outcome was major or any bleeding events and the secondary outcomes were stroke/systemic embolism (SE) and major adverse cardiac events (MACE). Of 1,068 participants, there were 264 (24.7%) patients in the combination group. The prevalence of diabetes (p=0.017) and history of stroke and transient ischemic attacks (p&amp;lt;0.001) was higher in the combination group than in the monotherapy group. During the mean 14.6±9.8 months of follow-up, the incidence of any bleeding was significantly higher in the combination group than in the monotherapy group (p&amp;lt;0.001). Major bleeding, stroke/SE, and MACE between the two groups were similar. The rate of under-dosage NOACs prescriptions was higher in the combination group than in the monotherapy group (p=0.024). Conclusions The combination therapy had higher incidences of any bleeding events compared to the monotherapy. However, there was no difference in stroke/SE and MACE. The bleeding risk in patients taking the combination of NOACs and APT should be carefully evaluated. Funding Acknowledgement Type of funding sources: None. Figure 1. Primary and secondary outcomes

Predicting the Risk of Ischemic Stroke in Patients Treated with Novel Oral Anticoagulants: A Machine Learning Approach

Introduction: The aim of this cohort study was to estimate the predictors of ischemic stroke in patients treated with non-vitamin K antagonist oral anticoagulants (NOACs) in a large database containing data from general practitioners in Germany using machine learning methods. Methods: This retrospective cohort study included 39,652 patients with a diagnosis of atrial fibrillation (AF) and an initial prescription of NOAC in 1,278 general practices in Germany between January 2011 and December 2018. Of 39,652 patients, 2,310 (5.8%) receive the first stroke or TIA diagnosis during the follow-up time (average follow-up time 2.5 [SD: 1.8] years). Sub-Population Optimization and Modeling Solutions (SOMS) tool was used to identify subgroups at a higher risk of stroke compared to the overall population receiving NOAC based on 37 different variables. Results: Using SOMS, a total of 9 variables were considered important for the stroke prediction. Age had 59.1% of prediction importance, following by ischemic heart diseases (10.6%), urinary tract infections (4.6%), dementia (3.5%), and male sex (3.5%). Further variables with less importance were dizziness (2.2%), dorsalgia (1.5%), shoulder lesions (1.1%), and diabetes mellitus (1.1%). Discussion/Conclusions: The stroke risk in AF patients treated with NOAC could be predicted based on comorbidities like ischemic heart diseases, urinary tract infections, and dementia additionally to age and male sex. Knowing and addressing these factors may help reduce the risk of stroke in this patient population.

Changes in anticoagulant prescription patterns over time for patients with atrial fibrillation around the world.

BackgroundPrescribing patterns for stroke prevention in atrial fibrillation (AF) patients evolved with approval of non‐Vitamin K antagonist oral anticoagulants (NOACs) over time.ObjectivesTo assess changes in anticoagulant prescription patterns in various geographical regions upon first approval of a NOAC and to analyze the evolution of oral anticoagulants (OACs) use over time in relation to CHA2DS2‐VASc and HAS‐BLED risk profiles.MethodsGlobal Registry on Long‐Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA‐AF) Phases II and III reported data on antithrombotic therapy for patients with newly diagnosed AF and ≥1 stroke risk factor. We focused on sites enrolling patients in both phases and reported treatment patterns for the first 4 years after initial NOAC approval.ResultsFrom GLORIA‐AF Phases II and III, 27 432 patients were eligible for this analysis. When contrasting the first year with the fourth year of enrolment, the proportion of NOAC prescriptions increased in Asia from 29.2% to 60.8%, in Europe from 53.4% to 75.8%, in North America from 49.0% to 73.9% and in Latin America from 55.7% to 71.1%. The proportion of Vitamin K antagonists (VKAs) use decreased across all regions over time, in Asia from 26.0% to 9.8%, in Europe from 35.5% to 16.8%, in North America from 28.9% to 12.1%, and in Latin America from 32.4% to 17.8%. In the multivariable analysis, factors associated with NOAC prescription were as follows: enrolment year, type of site, region, stroke and bleeding risk scores, and type and categorization of AF.ConclusionsDuring 4 years after the approval of the first NOAC, NOAC use increased, while VKA use decreased, across all regions.

The Importance of Appropriate Dosing of Nonvitamin K Antagonist Oral Anticoagulants for Stroke Prevention in Patients with Atrial Fibrillation

Preventing thromboembolic events, while minimizing bleeding risks, remains challenging when managing patients with atrial fibrillation (AF). Several factors contribute to current dosing patterns of nonvitamin K antagonist oral anticoagulants (NOACs), including patient characteristics, comorbidities, and physician judgment. Application of NOAC doses inconsistent with the drug labels may cause patients to receive either subtherapeutic (increasing stroke risk) or supratherapeutic (increasing bleeding risk) anticoagulant levels. In clinical practice, under- or over-dosing of NOACs in patients with AF is not uncommon. This analysis of prospective and retrospective registry and database studies on NOAC use in patients with AF (with at least 250 patients in each treatment arm) showed that under-dosing may be associated with reduced effectiveness for stroke prevention, with similar or even increased bleeding than with the standard dose. This may reflect underlying conditions and patient factors that increase bleeding despite NOAC dose reduction. Such factors could drive the observed overuse of reduced NOAC dosages, often making the prescription of reduced-dose NOAC an intentional label deviation. In contrast, over-dosing more likely occurs accidentally; instead of providing benefits, it may be associated with worse safety outcomes than the standard dose, including increased bleeding risk and higher all-cause mortality rates. This review summarizes the main findings on NOAC doses usually prescribed to patients with AF in clinical practice.

Rationale and design of a prospective, multicenter, cross-sectional study of appropriateness evaluation of the prescription of non-vitamin K antagonist oral anticoagulants for Chinese atrial fibrillation patients (Chi-NOACs-AF trial).

Non-vitamin K antagonist oral anticoagulants (NOACs) are alternative to vitamin K antagonists (VKAs) for stroke prevention in patients with atrial fibrillation (AF). Along with their widespread clinical use in China, the off-label use of NOACs is commonly seen in real-world practice, which could result in adverse drug events and poor clinical outcomes. However, guideline adherence and label adherence for NOAC prescriptions have not been well evaluated in a real-world setting in China. Between January 2021 and June 2021, a total of 1,750 outpatients or inpatients with AF will be consecutively enrolled at 26 canters in China. Data on patient demographics, clinical characteristics, treatment strategies, and prescribing information related to anticoagulation therapy for patients with AF will be collected. Clinical pharmacists will evaluate the rationality of the anticoagulation regimens and NOAC prescriptions based on the guideline recommendations and drug labels that are approved by the National Medical Products Administration. The primary outcomes will be the prevalence of irrational anticoagulation strategies and the inappropriate NOAC prescriptions, as well as potential risk factors associated with inappropriate prescriptions in patients with AF. This study will be the first national, multicenter, prospective study performed by pharmacists to explore real-world data on the appropriateness of NOAC prescription in Chinese patients with AF. The Chi-NOACs-AF trial (Trial number: ChiCTR2000035908).

Inappropriate dose of nonvitamin-K antagonist oral anticoagulants: prevalence and impact on clinical outcome in patients with nonvalvular atrial fibrillation.

Limited real-world data are available regarding the outcome of patients treated with inappropriate dose of nonvitamin-K antagonist oral anticoagulants (NOACs). To assess the prevalence and factors associated with inappropriate dose prescription of NOACs and to evaluate adverse events that come from this inappropriate prescription. Single-center multidisciplinary registry including nonvalvular atrial fibrillation patients treated with NOACs. Based on guidelines criteria for dose reduction, two subcohorts were defined as treated with appropriate or inappropriate NOACs dose. Primary efficacy endpoint was 2-year rate of thromboembolic events. Primary safety endpoint was 2-year rate of major bleeding. Event-free survival curves among groups were compared using Cox-Mantel test. A total of 760 nonvalvular atrial fibrillation patients were included; 32% patients were treated with dabigatran, 34% with apixaban, 24% with rivaroxaban and 10% with edoxaban. An inappropriate dose was prescribed in 96 patients (12.6%), and in most cases (68%) it was too low. Rivaroxaban (15%) and apixaban (18.5%) were the most frequently prescribed with an inappropriate dose. Patients treated with an inappropriate dose were elderly people, with low-creatinine clearance value, who had experienced previous bleeding and with a high CHADS2 VASc score. In 2 years, a trend for higher numbers of thromboembolic events (5.2 vs. 3.3%, P = 0.348) and less major bleeding (2.1 vs. 4.2%, P = 0.316) has been observed in patients with inappropriate NOACs prescriptions. Nearly 13% of patients were treated with an inappropriate dose of NOACs, in this single-center study. A trend for higher numbers of thromboembolic events was observed in these patients. The results should be considered as hypothesis generating.

Comparing the Effectiveness and Safety of Nonvitamin K Antagonist Oral Anticoagulants and Warfarin in Elderly Asian Patients With Atrial Fibrillation: A Nationwide Cohort Study

Stroke prevention in elderly patients with atrial fibrillation (AF) can be challenging, requiring a balance between thromboembolism prevention and serious bleeding. Comparisons of nonvitamin K antagonist oral anticoagulants (NOACs) and warfarin in older adults at different age strata (65-74, 75-89, and≥ 90 years of age) in the daily practice have not been well described, particularly in Asians. We aimed to assess the clinical outcomes of NOACs compared with warfarin for stroke prevention in elderly patients with AF. From 2012 to 2015, 64,169 patients≥ 65 years of age with AF who received at least one NOAC (dabigatran, rivaroxaban, or apixaban) or warfarin prescription were identified from the Taiwan National Health Insurance Research Database. The risks of ischemic stroke, intracranial hemorrhage (ICH), major bleeding, mortality, and composite adverse events were compared between NOACs and warfarin in all patients≥ 65 years of age and, specifically, with different age strata (ie, 65-74, 75-89,≥ 90 years). Overall, NOACs were associated with a significantly lower risk of ischemic stroke (adjusted hazard ratio [aHR], 0.869; 95%CI, 0.812-0.931), ICH (aHR, 0.524; 95%CI, 0.456-0.601), major bleeding (aHR, 0.824; 95%CI, 0.776-0.875), mortality (aHR, 0.511; 95%CI, 0.491-0.532), and composite adverse events (aHR, 0.646; 95%CI, 0.625-0.667) than warfarin. There was heterogeneity in treatment effect for NOACs vswarfarin in different age strata, but the results still favored NOACs even among very older adults (≥ 90 years). The results were generally consistent with propensity matching analysis. The absolute risk difference and reductions in ICH and composite adverse events with NOAC use were even greater among older adults than warfarin. Compared with warfarin, NOACs were associated with a significantly lower risk of adverse events, with heterogeneity in treatment effects among different age strata. Overall, the clear safety signal in favor of NOACs over warfarin was evident irrespective of age strata, being most marked in very older adults.

Discontinuation of non-Vitamin K antagonist oral anticoagulants in patients with non-valvular atrial fibrillation: a population-based cohort study using primary care data from The Health Improvement Network in the UK

ObjectiveTo determine discontinuation rates, patterns of use and predictors of discontinuation of non-vitamin K antagonist oral anticoagulants (NOACs) among patients with non-valvular atrial fibrillation (NVAF) in the first year of...

P4754Time to discontinuation of non-vitamin k antagonist oral anticoagulants in patients with non-valvular atrial fibrillation

Abstract Background Despite widespread use of non-vitamin K antagonist oral anticoagulants (NOACs), real-world data on time to discontinuation and time to re-initiation of the NOAC treatment are still scarce. Purpose To identify patterns of time to discontinuation as well as time to re-initiation of NOACs in patients with NVAF during the first year of treatment in UK primary care. Methods This population-based retrospective cohort study included 11,481 patients with NVAF, aged 18 and above, enrolled in The Health Improvement Network (THIN) with at least 1 year of follow-up after first recorded prescription of apixaban, dabigatran, or rivaroxaban between Jan 2012 to Dec 2016, and received two or more prescriptions of index NOAC. Discontinuation was defined as an interval greater than 30 days between the end of supply of the index NOAC and the date of the next prescription of the index NOAC. Discontinuers were further categorized as switchers, re-initiators or non-re-initiators. Re-initiators were patients who re-started OAC therapy after they discontinued treatment. Proportion of patients who discontinued NOAC treatment as well as mean duration (months) on treatment was calculated. Results The majority of patients were continuous users of their initial NOAC; discontinuation within the first year of treatment accounted for 26.1% of the apixaban cohort, 40.0% of the dabigatran cohort, and 29.6% of the rivaroxaban cohort. Time to discontinuation: Among discontinuers, the mean time patient stayed on initial treatment was the least for dabigatran (4.5 months), followed by apixaban (4.7 months) and highest for rivaroxaban (4.9 months). Discontinuers who did not later reinitiate any OAC therapy had a slightly longer time to discontinuation (mean 5.5 months) than those who later reinitiated OAC therapy (either on the same NOAC, a different NOAC or VKA; mean 4.6 months), or who switched treatment (4.0 months). Time to re-initiation: Among OAC reinitiators, no difference was seen in the time to re-initiation between NOACs (apixaban – 1.9 months, dabigatran – 2.1 months, and rivaroxaban – 2.0 months. Conclusion The proportion of discontinuation among new users of NOAC with NVAF in the first year was 30%. Average time on treatment for switchers, re-initiators and those who completely discontinued shows that such activities occurs around 4–5 months after initiating NOAC treatment, which is when further monitoring might be required. Once discontinued, re-initiation of NOAC treatment on average took 55–65 days. Acknowledgement/Funding The study is funded by Bayer AG

Inappropriate non-vitaminK antagonist oral anticoagulants prescriptions: be cautious with dose reductions.

BackgroundNon-vitamin K antagonist oral anticoagulants (NOACs) are prescribed to patients with atrial fibrillation (AF) to reduce the risk of stroke. Prescribing the correct dose warrants careful consideration of the prevailing dose criteria that differ per NOAC. Electronic systems are useful to intercept prescriptions that are incorrect based on simple ‘primary’ criteria, for example dosing frequency and drug-drug interactions with concomitant medication. However, these systems do not take into account patient characteristics such as age, renal function or weight, which are crucial elements to determine the NOAC dose.MethodsOur goal was to determine the appropriateness of all prescriptions, as compared with the product labelling approved by the European Medicines Agency, to address common pitfalls in prescribing NOACs. AF patients with a first NOAC prescription between January 2012 and December 2016 were identified from our electronic hospital information system (Martini Hospital, Groningen, the Netherlands).ResultsThe study included 3,231 AF patients who had started on an NOAC; 10.7% received an inappropriate dose and the appropriateness of the prescription could not be determined in 14.1%. Underdosing and overdosing occurred in 5.4% and 4.5% of all prescriptions, respectively. A reduced-dose NOAC was a predictor for incorrect prescribing (odds ratio: 2.70, 95% confidence interval: 2.13–3.41). Patient factors were identified that predicted incorrect prescriptions for dabigatran and apixaban.ConclusionAn incorrect prescription occurred more often in the reduced-dose NOAC group. Clinical parameters such as renal function are often unknown whilst these are essential to determine the right NOAC and dose.Electronic supplementary materialThe online version of this article (10.1007/s12471-019-1267-9) contains supplementary material, which is available to authorized users.

Non-Vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Atrial Fibrillation Patients With Intracerebral Hemorrhage.

Background and Purpose- Recurrent bleeding associated with oral anticoagulants (OACs) causes a dilemma in patients with atrial fibrillation (AF) sustaining an intracerebral hemorrhage. Treatment recommendations guiding clinical practice on optimal OAC agent selection in this population are lacking. This study aimed to investigate the comparative effectiveness and safety of non-vitamin K antagonist OAC (NOAC) versus warfarin in patients with AF sustaining an intracerebral hemorrhage. Methods- We conducted a nationwide observational cohort study including patients with AF sustaining an intracerebral hemorrhage and who subsequently claimed an OAC prescription. Contrasts of 1-year risks for ischemic stroke and intracerebral hemorrhage risks were obtained and evaluated by inverse probability treatment weighted absolute risk reduction and risk ratios. Results- Among 622 AF patients with intracerebral hemorrhage, 274 claimed a warfarin prescription and 348 a NOAC prescription. Mean age was 76 years (39% females); 72% had an index nonsevere event and 28% moderate to severe index event according to the Scandinavian Stroke Severity scale. The 1-year ischemic stroke risk was 7.85% for warfarin and 4.01% for NOACs, with a weighted absolute risk reduction of 3.78% (95% CI, -0.15% to 7.71%); the weighted risk ratio was 0.52 (0.27-1.00). For recurrent intracerebral hemorrhage, the risk was 7.00% for warfarin and 5.07% for NOACs. The absolute risk reduction was 1.93% (-2.02% to 5.87%), with an a weighted risk ratio of 0.72 (0.38-1.38). Conclusions- NOACs were associated with a nonsignificant lower risk of ischemic stroke and recurrent intracerebral hemorrhage compared with warfarin. The results add to current recommendations of selecting a NOAC agent for stroke prophylaxis treatment in patients with AF, including those with sustaining an intracerebral hemorrhage.

Tailored Practical Management of Patients With Atrial Fibrillation: A Risk Factor-Based Approach.

The management of antithrombotic therapy for thromboprophylaxis in patients with atrial fibrillation (AF) has been recently evolved by the progressive replacement of vitamin K antagonists with the non-vitamin K antagonist oral anticoagulants (NOACs). However, while these drugs are effective in reducing ischemic stroke/systemic embolism, a still high rate of cardiovascular events is present in the AF population. A tailored integrated approach to patients with AF is therefore necessary to reduce both thromboembolic events and cardiovascular disease. This approach should consist in the assessment of individual risk factors for ischemic and bleeding events in order to choose the most appropriate anticoagulant treatment according to patient's characteristics and preference. To this purpose, several risk scores have been developed and validated to stratify thromboembolic and hemorrhagic risk. This review provides an individual-based strategy for the management of patients with AF, from a risk-factor based approach to a tailored prescription and monitoring of NOACs. In particular, we reported an updated practical management strategy for AF patients in specific clinical situations such as those (1) experiencing a major bleeding, (2) requiring a switch to another antithrombotic regimen, (3) restarting anticoagulation after acute ischemic stroke, (4) suffering from an acute coronary artery disease (acute coronary syndrome or undergoing cardiac revascularization).

Identifying Factors That Predict the Prescription of Non–vitamin K Antagonist Oral Anticoagulants in Older Individuals With Atrial Fibrillation

ObjectivesFactors that influence decision of non–vitamin K antagonist oral anticoagulants (NOACs) use among older atrial fibrillation (AF) patients in long-term care (LTC) facilities have not been well studied. The aim of this study was to assess whether increased frailty influenced physicians to prescribe NOACs over warfarin. DesignWe retrospectively reviewed the electronic medical record (EMR) and pharmacy data of 25 LTC facilities in Ontario, Canada, in May 2015. The diagnosis of AF was ascertained from EMR and confirmed by complete chart review of a random sample of the cohort. A score of ≥2 on the Changes in Health, End-stage disease, Signs, and Symptoms (CHESS) scale was used as a surrogate marker of frailty. MeasuresMultivariable logistic regression model was used to assess whether a higher frailty score is associated with the use of NOACs in comparison to warfarin, independent of potential patient-level confounders. Setting and participantsIn total, 3378 active residents were assessed in 25 LTC facilities. All the residents were ≥65 years old. We identified 433 residents with AF; 273 (63%) AF residents were on anticoagulation therapy and included in the analysis. ResultsResidents were more often treated with NOACs (n = 159; 58%) in comparison to warfarin (n = 114; 42%). A CHESS score of ≥2 increased the odds of prescribing NOACs by 2.46 times [95% confidence interval (CI) 1.11, 5.49; P = .03] when adjusted for important patient-level factors. Patients with hypertension had a trend of increased NOAC prescriptions but did not reach statistical significance [odds ratio 2.1 (95% CI 0.91, 4.81), P = .08]. None of the patient-level factors were associated with NOAC prescriptions. Conclusions and ImplicationsIn this real world cohort of AF patients in LTC who are prescribed an oral anticoagulation therapy, a higher CHESS score (≥2) is associated with increased use of NOACs in comparison to warfarin.

2018 KHRS Practical Guide on the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Korean Patients with Atrial Fibrillation: How to Initiate and Organize the Follow-up

Non-vitamin K antagonist oral anticoagulants (NOACs) are alternatives to vitamin K antagonists to prevent stroke in patients with non-valvular atrial fibrillation (AF) and have emerged as the preferred choice. The use of NOACs is rapidly increasing in Korea after coverage by insurance since 2015. However, the rate of prescribing anticoagulants in Korean patients with AF remains low compared to other countries. Most of the NOAC anticoagulant prescriptions are issued at hospitals. As the prevalence rate of AF in Korea is expected to increase rapidly with the increase in the elderly population, the need to prescribe NOACs in primary care clinics will also increase. Therefore, The Korean Heart Rhythm Society organized the Korean Atrial Fibrillation Management Guideline Committee and analyzed all available studies based on the 2018 European Heart Rhythm Association Practical Guide on the use of NOACs for managing AF, as well as studies on Korean patients. The authors would like to introduce practical guidelines for NOAC prescriptions in Korean patients with AF. (Korean J Med 2019;94:17-39)