Dabigatran has the lowest percentage of doses consistent with the guidelines, with 46.5% of patients being medicated with a lower dose inconsistent with the guidelines. Patients who are 75 years old or younger, have a GFR greater than 60 mL/min and whose renal function should be monitored annually have the highest percentage of an adequate range of GFR. Other groups who require closer GFR monitoring have a lower percentage of an adequate range of GFR. Adherence to NOACs varies with different drugs: there was greater adherence to treatment with edoxaban and less adherence to apixaban.

Antunes et al evaluated the prescription of OAC in four family health units in Northern Portugal from January 2010 to December 2015. They found that 76.7% of patients diagnosed with AF based on ICPC-2 coding were medicated with OAC.14 However, in the period from 2016 to 2018, there was an increase in prescriptions to 98%. This suggests an improvement in the anticoagulation of patients with AF in the northern region of Portugal over the years. These results contradict some European studies that showed resistance from family physicians to introduce anticoagulation after the diagnosis of AF,15–18 and contradict the findings of the study by Turakhia et al, which showed that the medical specialty that diagnoses AF influences the decision to anticoagulate or not.19

The electronic clinical files of primary healthcare contain a list of health problems for which there is a follow-up plan, relevant diseases and those who require continuous medical treatment. Accurate records ensure the adequacy of care and enable monitoring and evaluation of the care provided to the population.20 The use of the ICPC-2 is essential for this purpose. Data published in 2015 by the Central Administration of the Health System (CAHS) showed a growing codification of health problems at a national level, reflecting the increase in computerised clinical records and demand from users and healthcare providers.21 This study found that the ICPC-2 K78 encoding has become more frequent over the years, which is consistent with the CAHS data at the national level. In 2011, 20.6 million health problems were identified, and by 2013, this figure had increased to 30.2 million. The percentage of consultations with ICPC-2 coding in primary healthcare is high in Portugal (69.2% in 2011, 83.9% in 2012 and 84% in 2013).21

Sugrue et al found that NOAC dosing was inconsistent with the guidelines in 14.8% of patients at the Mayo Clinic: 12.4% received an inappropriate lower dose and 2.4% received a higher dose inconsistent with the guidelines.22 Even the ORBIT-AF II Registry, a nationwide AF registry conducted in a community practice in the USA, showed that a dose of NOAC inconsistent with the guidelines was prescribed in only 12.5% of cases: underdosing in 9.3% of patients and overdosing in 3.3% of patients, respectively.23 However, a real-world registry in Spain reported higher rates of underdosing and overdosing on NOAC therapy: 17.5% and 14.9%, respectively.24 This study’s results agree with those of the Mayo Clinic and ORBIT-AF II Registry Studies, with underdosing in 15.1% and overdosing in 1.8% of patients. These findings are consistent with studies conducted in other countries. Similar to studies carried out in other countries, in Portugal, taking into account that this study included patients from primary healthcare in the northern region, the same prescription profile can be considered throughout the entire National Health Service. So, due to the risks associated with prescribing inconsistent with the guidelines, greater attention is needed from Portuguese family doctors, emphasising the need for collaboration with health planners to implement a medical educational agenda. This agenda aims to enhance the knowledge and practices related to anticoagulation, possibly addressing issues such as proper prescription, monitoring and management of anticoagulant therapy.

Stamellou and Floege highlighted the importance of regular checks of renal function in patients receiving NOACs to avoid overdosing, especially in situations that may cause acute-on-chronic kidney injury. In such patients, apixaban may be the safest licensed NOAC because of its relatively low renal elimination. In more advanced CKD, that is, stage 4 and particularly in stage 5, NOACs are not recommended due to the lack of randomised controlled trial data and concerns of overdosing with the risk of bleeding and anticoagulant-related nephropathy.25 A prudent approach is to check renal function at the initiation of treatment with NOACs, after 3 months and then every year, except for high-risk patients (the elderly >75 years, patients with low body mass) who require monitoring at least every 6 months.26 In patients with declining renal function, the current position of EHRA is to estimate the recheck intervals individually using a simple calculation: if CrCl is ≤60 mL/min, the recheck interval in months is CrCl/10.11

Andreu Cayuelas et al assessed compliance with kidney function monitoring recommendations in patients with non-valvular AF starting NOAC therapy.27 Compliance with kidney function monitoring recommendations was 61%, similar to the group of patients younger than 75 years with a GFR >60 mL/min in this study. Patients younger than 75 years with a GFR >60 mL/min had the highest rate of adequate GFR range, at about 60%, followed by patients ≤75 years old with a GFR <60 mL/min at 29.4% and patients >75 years old at 27.8%. Another noteworthy finding is the low percentage of patients with a GFR range assessed beyond the appropriate 12-month interval in patients >75 years old and in patients ≤75 years old with a GFR <60 mL/min (10.4% and 10.2%, respectively). Family doctors appear to follow an annual pattern for monitoring renal function in all patients receiving NOACs, without individualising the interval for monitoring renal function according to the criteria mentioned here. Therefore, patients who receive annual GFR evaluations have the highest rate of adequate renal monitoring. More training for individualised tracking of patients with other conditions may help Portuguese family doctors improve these results.

There was greater adherence to treatment with edoxaban and less adherence to apixaban, likely due to differences in drug posology, with edoxaban taken once daily and apixaban taken two times per day. Brízido et al evaluated adherence to NOACs and its determinants in a population of patients with AF from the outpatient general cardiology list at a tertiary centre in Portugal. The median adherence was 91% (IQR 74–100%) for rivaroxaban, 87% (IQR 74–100%) for apixaban, 82% (IQR 48–100%) for dabigatran and 96% (IQR 83–100%) for edoxaban. There were no statistically significant differences between the NOACs (p=0.102). Half of the patients (51%) were classified as non-compliant, which is consistent with the findings of this study. It was found that in all NOACs, with the exception of dabigatran, adherence was higher in patients diagnosed after the start of the study than in those diagnosed before the start of the study who had a longer duration of therapy. Therefore, there appears to be greater adherence in the immediate period after the diagnosis than in a later period. Therapy duration, NOACs taken two times per day and higher out-of-pocket costs were independent predictors of non-compliance.12

In another real-world analysis of adherence to NOACs, rivaroxaban and apixaban had favourable profiles compared with dabigatran, and rivaroxaban appeared to have higher overall adherence among the NOACs, although edoxaban was not included in this analysis.28 A systematic review and meta-analysis of observational studies found that up to 30% of patients with AF are non-adherent to NOAC therapy.29 Although we analysed data on drug dispensing in pharmacies, there may be the possibility of patients forgetting to take medication, which is more likely to occur with drugs taken two times per day (apixaban and dabigatran), so medication usage by the patients was not verified.

The primary limitation of the AF-React Study is that it relies on AF assessment data coded during the clinical process in primary healthcare. While there are some defects in the coding, it appears that the ICPC-2 K78 encoding has become more common over the years, and since 2015, there has been a decrease in the number of AF diagnoses coded. This suggests that the increase in K78 encoding is related to real new diagnoses rather than simply detecting coding errors in previous diagnoses.

When assessing the appropriateness of the prescribed NOAC dose, only the most recent GFR, weight and age criteria were considered. Unfortunately, other relevant NOAC dosage criteria were not available in the database, namely, the concomitant use of other drugs. It is also important to consider frailty when assessing the appropriate range of GFR to monitor renal function and prescribe NOACs. However, these data were not available for analysis.