GARFIELD-AF was the largest, worldwide, prospective registry of newly diagnosed AF patients. In the Netherlands, 1189 patients were enrolled, making it the largest Dutch AF-cohort available to date. This manuscript provides a unique insight in the rapid changes in anticoagulation management of novel AF, which had not been described since the introduction of the NOACs in the Netherlands. The comparison between NOAC uptake rates in the Netherlands vs other countries is important, as this could have influenced the quality of Dutch AF care. Future studies will have to analyze how these differences have impacted the safety and efficacy of AF care. Moreover, this is the first report describing nationwide adherence to AF-guidelines in the Netherlands and explores reasons for withholding oral anticoagulation in AF, which gives insight in how to further improve our AF care. Also, this country-specific evaluation may also be of help in improving care when comparisons are made with anticoagulant management in other countries.
In the Netherlands, there was initially a slow shift to more NOAC prescription, compared to the rest of the world. However, as of 2014–2015, the anticoagulation landscape has changed rapidly, resulting in more newly diagnosed AF patients treated with NOACs than VKA as of 2016. Our findings were comparable to a recent analysis of anticoagulant pharmaceutical dispensing data of naïve oral anticoagulation starters for any indication in the Netherlands [15]. A possible explanation for this initial slow shift could be that there is a well-organized system of specialized anticoagulation clinics in the Netherlands. In these clinics, the monitoring of compliance and complications of VKA treatment through regularly scheduled follow-up checks is aimed at minimising risks accompanying VKA treatment. Although NOACs have been repeatedly shown to be at least as effective and safe as VKAs in both randomized controlled trials and real-world data, a lack of monitoring could have contributed to a hesitation to shift to a more NOAC based approach. This is not unreasonable, as without a regular check of factors such as renal function, weight or age, patients are often (± 10% in two recent Dutch AF-studies), treated with a too high or too low NOAC dose [16, 17]. Moreover, early discontinuation of (N)OAC treatment can be as high as 50% at 6 months in certain patient groups [18, 19]. Frequently mentioned reasons for early discontinuation are (minor) bleeding, other anticoagulant-related side-effects, and a lack of the perceived need for anticoagulation [20, 21]. Therefore, international guidelines recommend structured follow up of patients on NOACs (ESC) including assessment of adherence to medication, complications, interactions and regular (at least annual, but more often on indication) check on renal and liver functions [22]. For the Netherlands, much of this burden will come down on the shoulders of prescribers (mainly cardiologists) and for the long term on general practitioners. It is imperative that, based on national guidance documents such as the “Landelijke Standaard Ketenzorg Antistolling” (LSKA) 2.0 and the updated “Landelijke Transmurale Afspraak antistolling” (manuscript in preparation), the chronic care for patients on NOACs becomes well organized [23].
In GARFIELD-AF, the Netherlands had the highest proportion of patients on oral anticoagulation at diagnosis (89.9%). In the most recent cohort, Dutch patients had the lowest proportions of antiplatelet monotherapy (2.5%) or no antithrombotic therapy (1.9%). For patients with a class I recommendation for anticoagulation, 7.5% of patients were undertreated according to the ESC guidelines [10]. Compared to the worldwide cohort (30.0%), this proportion is relatively low. In patients with a class III recommendation for anticoagulation (i.e. CHA2DS2-VASc 0 in males, CHA2DS2-VASc 1 in females), the proportion of patients on anticoagulation is high (66.6%) [10]. Although there is no chronic indication for anticoagulation in these patients, the guideline recommends at least 3 weeks of pre-treatment with oral anticoagulation in late cardioversions [10]. The ACWAS trial showed that in patients with recent-onset (< 36 h) AF, a delayed cardioversion strategy led to spontaneous conversion within 48 h in 69% of patients [24]. In a post-hoc analysis of the ACUTE trial, nearly 50% of patients with pre-existing AF of ≤1 week had a spontaneous cardioversion [25]. It is likely that patients with recent-onset, newly diagnosed AF without risk factors for stroke are often ‘overtreated’ with anticoagulation, given the high rate of spontaneous conversion. It is therefore worth researching if there are possibilities to safely limit the prescription of anticoagulants in these patients.
Although the proportion of undertreated patients in the Netherlands was relatively low, there is still room for improvement. In GARFIELD-AF, main reasons for not prescribing anticoagulants in patients with a class I recommendation for anticoagulation for stroke prevention in AF were often not clear. In patients with a clear recorded reason for withholding anticoagulation, a ‘low risk of stroke’ (12.1%) and ‘bleeding risk’ (7.6%) were the most common reasons in the Dutch cohort. Depicting patients with 2 or more non-sex related stroke risk factors as having a ‘low risk of stroke’ is contradictory, and the precise reasoning behind it is unknown. It would be valuable to gather more information on reasons for withholding anticoagulation, and to evaluate if withholding anticoagulation in these groups is a safe approach.
This study has several limitations. As described before, the high proportion of patients included in Dutch cardiology departments limits the external validity of this study to nationwide clinical practice. Moreover, the number of patients was too low, and the mean follow-up was too short, to relate major adverse events to CHA2DS2-VASc scores or changes in anticoagulant treatment practices. Moreover, reasons for not prescribing anticoagulants were extracted from the medical records and were not confirmed by the prescribing physician, and a large proportion of reasons could not be recorded and were classified as ‘other’. Further research without these limitations is necessary. DUTCH-AF (Dutch trial register number: NL7464) is a largescale registration of newly diagnosed AF-patients in the Netherlands, which does not have these limitations and could provide further answers [26].