A substantial increase in overall adherence to OAC for patients with AF was observed during the study period, rising from 53% in 2013 to 78% in 2022. Adherence improved consistently across all five Danish regions, without notable changes in the relative rankings of the regional adherence levels. By 2022, the absolute adherence difference between the highest-performing and lowest-performing regions was 7.6%. Concurrently, a significant shift in treatment patterns was observed, characterised by a transition from VKAs to DOACs, with a preference for rivaroxaban and apixaban. The sequential adjustments for patient demographics, health status and socioeconomic factors had little impact on the IRRs of OAC adherence across regions. The greatest impact of adjusting for patient characteristics was observed in 2013 when the adherence gap between the highest-performing and lowest-performing regions was reduced from 21% to 18%. When applying the fully adjusted regression model, the variation in adherence between the highest-performing and lowest-performing regions decreased from 18% in 2013 to 9% in 2022. However, the relative rankings of regions remained unchanged. Low socioeconomic status and the presence of psychiatric comorbidities were associated with reduced adherence to OAC, with the impact being more pronounced in regions characterised by lower overall adherence. Conversely, patients with multimorbidity showed higher adherence across all regions, with the highest impact in the Region of Southern Denmark and the Capital Region of Denmark.

The nationwide Danish registers provide comprehensive, high-quality data on health and sociodemographic characteristics with near-complete population coverage,23 thereby minimising selection bias and enabling robust and representative analyses. Health data are systematically collected over time from routine care settings, which allows the study of treatment patterns that reflect real-life practices and patient adherence. However, the use of routinely collected data inherently limits the depth of available information, as it is restricted to pre-existing data fields. Key clinical factors, such as patient-reported adherence barriers, physician rationale for treatment decisions and lifestyle factors, are not systematically recorded. As a result, important determinants of adherence remain unmeasured, potentially introducing residual confounding. Furthermore, despite systematic data collection, variations in coding practices over time and across administrative settings with different IT systems may introduce bias and lead to misclassification. The DNPR24 records all medication prescriptions redeemed at any pharmacy in Denmark. This ensures consistent, population-wide monitoring of medication reimbursement. However, as only data on redeemed prescriptions are available (not records of prescribed medications), the study relies on estimated daily doses. Furthermore, it cannot determine whether non-adherence was due to medications not being collected or never prescribed.

Our study demonstrated a substantial restructuring of anticoagulant treatment in Denmark over the past decade; this restructuring was characterised by significantly improved adherence and effective DOAC implementation. These findings are consistent with previous studies.6 7 18 19 However, our incorporation of recent data further highlighted the trends. During the study period, adherence increased consistently across all regions, and the absolute difference in adherence rates across regions decreased slightly, from 10% in 2013 to 7.6% in 2022. Furthermore, the adoption of DOACs followed a uniform pattern across regions. Such uniform development could be explained by the context of the Danish tax-funded healthcare system with free and equal access.37 Additionally, widely accepted international guideline recommendations exist for OAC.4 5 These guidelines have been translated and adapted to the Danish setting by the Danish Society of Cardiology and are updated annually (nbv.cardio.dk). They are widely implemented across geographical regions and healthcare sectors, thereby facilitating consistent treatment practices.

Although the implementation of DOACs was uniform across regions, variations in the preference for specific DOAC subtypes were observed. Rivaroxaban and apixaban were the predominant DOACs in all regions, but their distribution varied. Previous research has shown that once-daily dosing regimens are associated with improved adherence.38 39 In this study, DOACs with a once-daily dosing schedule (rivaroxaban and edoxaban) accounted for a larger proportion of dispensed prescriptions in regions with higher adherence rates, potentially contributing to regional variations in adherence.

The risk of suboptimal treatment varies depending on the patients’ comorbidity40–42 and sociodemographic characteristics.43 44 Previous studies on geographical variation in OAC initiation and persistence in Denmark have mainly focused on accounting for physical comorbidity and not for sociodemographic factors or mental health disorders.16 18 19 21 We aimed to explore to what extent geographical variation can be explained by differences in population characteristics across regions. Therefore, we applied regression models that sequentially adjusted for patient demographics, health status and socioeconomics to examine whether accounting for specific patient characteristics significantly changed the relative differences in adherence across regions. As the relative differences remained stable across all adjustment models, this suggests that differences in patient populations across regions explained little of the observed regional variation.

When applying the fully adjusted model over 10 years, we observed that the relative differences across regions (figure 4) showed the same pattern as the absolute differences (figure 2). The relative rankings of the regions remained unchanged, and a 9% difference in relative adherence rates was seen between the highest-ranked region compared with the lowest-ranked region. The reduced relative difference over time (figure 4) appeared more pronounced than the change in absolute rates (figure 2). However, this can largely be explained by the overall increase in adherence over time, which inherently will reduce the relative difference.

The inability of the applied models to explain regional variation may be due to several factors. First, many patient-related factors are not captured in the register-based data used in this study, including health literacy and beliefs about medication. Second, regional variation may be driven by provider-level and system-level factors, including differences in physicians’ adherence to guidelines, shared decision-making practices and resource allocation. When assessing if OAC variation was explained by differences in patient populations, we assumed that the impact of patient determinants was uniform across the entire population. Importantly, many factors at provider or system level can influence whether patient risk factors are associated with reduced adherence. Therefore, we investigated whether the impact of comorbidity and socioeconomic status varied according to the patient’s region of residence.

In line with existing literature, we found that non-Western origin,43 low income,44 living alone44 and having a mental health disorder40 were associated with an increased risk of non-adherence. Furthermore, we found that the risk of non-adherence associated with low income, living alone and having a mental health disorder was increased in the regions with the lowest adherence rates. This might indicate systematic differences in the management of vulnerable patient groups, which could contribute to the persistent variation.

We found that adherence rates were consistently higher in patients with multimorbidity across all regions. This finding contrasts with evidence suggesting that the complexity of care associated with multimorbidity, including the burden of polypharmacy, may negatively impact adherence.42 45 46 However, in patients with AF, the risk of ischaemic stroke (and the net benefit of OAC) increases with greater comorbidity.4 5 This could explain the higher OAC adherence seen among patients with multimorbidity and AF. The impact of multimorbidity varies across regions. However, the direction of these differences does not explain the inter-regional variation.

The observed increase in overall adherence to OAC among patients with AF is encouraging. Adherence rates appear to stabilise at approximately 80%, suggesting that the target for optimal treatment coverage may be nearing. However, our findings highlight persistent regional adherence disparities that cannot be explained by population differences alone. In some regions, vulnerable patient groups seem to face an elevated risk of non-adherence, which may result from systematic variations at healthcare provider level or system level.

Future studies should aim to identify drivers of regional variation to pinpoint opportunities for improvement at both healthcare provider level and system level. The persistent unwarranted geographical variation in OAC usage suggests that there is still opportunity and need for improving the quality and equity of care for patients with AF.