Adherence and Persistence with Once-Daily vs Twice-Daily Direct Oral Anticoagulants Among Patients with Atrial Fibrillation: Real-World Analyses from the Netherlands, Italy and Germany

Smits, Elisabeth; Andreotti, Felicita; Houben, Eline; Crijns, Harry J.G.M.; Haas, Sylvia; Spentzouris, George; Schink, Tania; Gini, Rosa; Bartolini, Claudia; Beest, Fernie J. A. Penning-van; Herings, Ron M. C.

doi:10.1007/s40801-021-00289-w

Cited by 17 publications

(11 citation statements)

References 33 publications

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“…Several previous studies have shown that NOAC adherence requiring twice-daily dosing was lower than that of once-daily dosing [ 8 , 10 ]. However, some studies individualizing each NOAC showed that the adherence to apixaban was similar to that of rivaroxaban, whereas dabigatran had lower adherence than apixaban or rivaroxaban [ 7 , 11 ], although both apixaban and dabigatran require twice-daily dosing.…”

Section: Discussionmentioning

confidence: 99%

Adherence and clinical outcomes for twice-daily versus once-daily dosing of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: Is dosing frequency important?

et al. 2023

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Background Twice-daily dosing of non-vitamin K antagonist oral anticoagulants (NOACs) may reduce drug adherence compared with once-daily dosing of NOACs in patients with atrial fibrillation (AF), thus worsening clinical outcomes. We evaluated adherence to apixaban and dabigatran requiring twice-daily dosing compared with edoxaban or rivaroxaban with a once-daily dosing regimen and the subsequent clinical outcomes in patients with AF. Methods Adherence to each NOAC and outcomes were compared between patients who were diagnosed with AF and initiated NOACs between 2016 and 2017 using Korean claims data. High adherence was defined as the proportion of days covered (PDC) of the index NOAC ≥80%. The clinical outcomes included stroke, acute myocardial infarction, death, and composite outcome. Results A total of 33,515 patients were analyzed (mean follow-up, 1.7 ± 1.3 years). The proportion of patients with high adherence to NOACs was 95%, which did not significantly differ according to the dosing regimen. The mean PDC for NOACs was as high as ~96%, which was the highest for apixaban users, intermediate for edoxaban or rivaroxaban users, and lowest for dabigatran users, regardless of the dosing regimen. Adverse outcomes in low adherence patients for each NOAC were higher than that of high adherence patients, regardless of the dosing frequency. Conclusions Adherence between once- and twice-daily dosing NOACs in patients with AF was high and similar among both dosing regimens. Patients with low NOAC adherence had poorer clinical outcomes, regardless of the dosing frequency.

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Section: Discussionmentioning

confidence: 99%

Adherence and clinical outcomes for twice-daily versus once-daily dosing of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: Is dosing frequency important?

et al. 2023

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“…In InGef and PHARMO, in case of an interruption between DOAC dispensings, use of DOACs was considered uninterrupted if the duration of this gap was less than half the duration of the preceding dispensing with a minimum of 7 days [ 20 ]. In ARS, use of DOACs was considered uninterrupted if the duration of the gap was 90 days or less, as in a previous study it was concluded that this method best fitted the ARS data [ 21 ]. Patients could have several treatment episodes after CED.…”

Section: Methodsmentioning

confidence: 99%

Increased Risk of Stroke Due to Non-adherence and Non-persistence with Direct Oral Anticoagulants (DOACs): Real-World Analyses Using a Nested Case–Control Study from The Netherlands, Italy and Germany

Holthuis

Smits

Spentzouris

et al. 2022

Drugs - Real World Outcomes

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Background A high degree of adherence to direct oral anticoagulants is essential for reducing the risk of ischaemic stroke and systemic embolism in patients with atrial fibrillation, owing to the rapid decline in anticoagulation activity when doses are omitted (i.e. rebound effect). Objective We aimed to assess the relationship between non-adherence and non-persistence with direct oral anticoagulants and the incidence of ischaemic stroke in patients with atrial fibrillation. Methods A nested case–control study was conducted in the Netherlands, Italy and Germany among patients with atrial fibrillation starting direct oral anticoagulants between the drug approval date and the end of database availability. Patients with an ischaemic stroke during the follow-up were selected as cases and compared with matched controls (matched on age ± 5 years, sex, year of cohort entry date and CHA 2 DS 2 -VASc-score at cohort entry date). The cohort entry date was the first dispensing date. Study patients were those aged ≥ 45 years, with ≥ 1 year database history, ≥ 1 year follow-up and at least two direct oral anticoagulant dispensings after the cohort entry date. Adherence and persistence to direct oral anticoagulant treatment were defined as the proportion of days covered ≥ 80% or direct oral anticoagulant continuous use between the cohort entry date and the index date (i.e. date of ischaemic stroke), respectively. Results In The Netherlands, Italy and Germany, 105 cases and 395 controls, 1580 cases and 6248 controls, and 900 cases and 3570 controls were included, respectively. Odds ratios (ORs) for stroke among current users who were non-adherent compared to adherent users were 0.43 (95% confidence interval [CI] 0.09–1.96) in The Netherlands, 1.11 (95% CI 0.98–1.26) in Italy and 1.21 (95% CI 1.01–1.45) in Germany. The risk of stroke was significantly higher among non-persistent users compared with persistent users in all three databases [OR 1.56 (95% CI 1.00–2.44), OR 1.48 (1.32–1.65) and OR 1.91 (95% CI 1.64–2.22), respectively]. In The Netherlands and Germany, the risk of stroke was higher the longer a patient had stopped using direct oral anticoagulants. Conclusions Both non-adherence (in Germany) and non-persistence increased the risk of stroke, either using a once-daily or twice-daily regime. Supplementary Information The online version contains supplementary material available at 10.1007/s40801-022-00317-3.

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“…a large number of daily doses) might negatively influence adherence [15]. The once-daily dosing regimen was associated with better adherence as opposed to twice-daily in patients with atrial fibrillation receiving oral anticoagulants [33]. Adherence was decreased in patients taking many medications to treat their comorbidities, contributing to the forgetfulness of taking medications [4].…”

Section: Social Supportmentioning

confidence: 99%

Medication Adherence in Cardiovascular Diseases

Pham¹,

Nguyen²,

Tran³

et al. 2023

Novel Pathogenesis and Treatments for Cardiovascular Disease

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Cardiovascular disease is a significant cause of death globally. While effective long-term medications that reduce the risk of morbidity and mortality related to cardiovascular disease are readily available, nonadherence to prescribed medications remains a significant reason for suboptimal management. Consequently, this might lead to increased morbidity and mortality and healthcare costs. Medication nonadherence causes are myriad and complicated, with factors at the patient, healthcare provider, and health system levels. Many clinical trials have investigated interventions to target these factors for improving medication adherence, including improving patient education, testing behavioral interventions, implementing medication reminder tools, reducing medication costs, utilizing social support, utilizing healthcare team members, and simplifying medication dosing regimens. This book chapter describes factors influencing medication adherence and highlights the impact of varying levels of adherence on patients’ clinical and economic outcomes. We also summarize interventions for improving medication adherence in cardiovascular disease.

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Adherence and Persistence with Once-Daily vs Twice-Daily Direct Oral Anticoagulants Among Patients with Atrial Fibrillation: Real-World Analyses from the Netherlands, Italy and Germany

Cited by 17 publications

References 33 publications

Adherence and clinical outcomes for twice-daily versus once-daily dosing of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: Is dosing frequency important?

Adherence and clinical outcomes for twice-daily versus once-daily dosing of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: Is dosing frequency important?

Increased Risk of Stroke Due to Non-adherence and Non-persistence with Direct Oral Anticoagulants (DOACs): Real-World Analyses Using a Nested Case–Control Study from The Netherlands, Italy and Germany

Medication Adherence in Cardiovascular Diseases

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