Contemporary management of patients with atrial fibrillation in the Netherlands and Belgium: a report from the EORP-AF long-term general registry

Data were analysed with SPSS statistical software (version 23.0, SPSS Inc., IBM Corp., Armonk, NY, USA). Continuous variables are reported as mean ± standard deviation if normally distributed and as median and interquartile range if not. Normally distributed continuous variables were compared between groups using the independent samples t‑test, whereas not normally distributed continuous variables were compared using the Mann-Whitney U test. Categorical variables are reported as observed number of patients and percentage. Among-group comparisons were made using a χ² test. Fisher’s exact test was used in case of any expected cell count < 5.

At baseline, the majority of the patients were on a rhythm control strategy according to the treating physician (n = 565, 58.6%), whereas 326 patients (33.8%) were on a rate control strategy. For the remainder of the patients (n = 73, 7.6%), no decision regarding the treatment strategy had been made yet.

In total, 354 patients (36.7%) were prescribed an anti-arrhythmic drug (AAD) for daily use and 653 (67.7%) a rate control drug (Tab. 2). Belgian patients were more frequently on AAD therapy (47.5% vs 31.4%, p < 0.001) with significantly more amiodarone users compared with their Dutch counterparts (28.3% vs 5.9%, p < 0.001), whereas Dutch patients more often received sotalol (17.2% vs 9.4%, p = 0.001). The prescription rates for the other AADs were comparable (Tab. 2). For rate control drugs, only digoxin use was significantly different between the two countries, with more frequent prescription in the Netherlands (19.5% vs 4.7%, p < 0.001).

Of the 565 patients with rhythm control as treatment strategy, 313 patients (55.4%) were on daily AAD treatment. In the remainder of patients, 14 (5.6%) were planned for electrical cardioversion and 1 (0.4%) for surgical AF ablation, meaning that 237 patients (41.9%) were on a rhythm control strategy without daily AAD use or a planned rhythm intervention.

Of the 326 patients with rate control as treatment strategy, 280 patients (86.2%) were on rate control drugs, whereas 45 (13.8%) were not (for 1 patient medication was missing). Notably, 34 of the 326 patients with rate control as treatment strategy (10.4%) were on daily AAD treatment. In the remainder of patients, 4 (1.4%) were planned for electrical cardioversion, meaning that 38 patients (11.8%) were wrongfully classified as rate control and should in fact have been classified as rhythm control regarding the treatment strategy.

At baseline, 887 patients (91.9%) received anticoagulant treatment, with a larger proportion of patients using a non-vitamin K antagonist oral anticoagulant (NOAC) in Belgium than in the Netherlands (54.4% vs 38.4%). Fig. 1 depicts the percentage of patients with and without anticoagulation for the different CHA₂DS₂-VASc (congestive heart failure, hypertension, age ≥ 75 years [doubled], diabetes mellitus, prior stroke [doubled], vascular disease, age 65–74, sex category) scores, also specifying the type of anticoagulant. For men with CHA₂DS₂-VASc 0 and for women with CHA₂DS₂-VASc 1, the anticoagulation rates were 71.6% (68/95 patients) and 66.7% (20/30 patients) respectively. In these patients with anticoagulation, a rhythm intervention was performed during the baseline assessment or planned for the near future in 45 men (66.2%) and 7 women (35%). The remaining 23 men (33.8%) and 13 women (65%) were on anticoagulant treatment without a clear indication (Fig. 2).

For patients with NOACs, over- and underdosing of NOACs were checked according to the dose reduction criteria for the respective drug [6]. In total, 14 patients were prescribed the full dose for a NOAC, whereas they should have received the reduced dose according to the Summary of Product Characteristics (SmPC). This was the case for 12/148 patients with rivaroxaban and 2/57 with dabigatran (“Overdosed NOAC” in Fig. 2). No overdosing was present for both apixaban (n = 70) and edoxaban (n = 5). Underdosing occurred in 49 patients (“Underdosed NOAC” in Fig. 2), i.e. 38/50 patients with apixaban, 8/24 with rivaroxaban, and 3/30 with dabigatran. Reduced dose of edoxaban was not prescribed. In total, 63 (16.7%) of 372 patients were not correctly dosed.

Rhythm follow-up was available in 839 patients (86.8%). AF progression and AF regression occurred at a similar rate, with 57 (17.3%) of 329 patients with paroxysmal AF at baseline progressing into persistent or permanent AF after one year of follow-up and 87 (17.6%) of 494 patients with persistent or permanent AF regressing into paroxysmal AF. Of the regressors, 38 patients (43.7%) were already on AAD treatment at baseline. A rhythm intervention was performed during follow-up in 20 (23.0%) of 87 patients showing regression, i.e. in 12 patients (13.8%) an AAD was initiated, in 9 patients (10.3%) a catheter ablation for AF was performed (1 of whom also started AAD therapy), and in 2 patients (2.3%) surgery for atrial fibrillation was performed (both of them started AAD therapy as well). The remaining 67 patients (77%) showed regression in type of AF without rhythm intervention.

In total, 233 (26.4%) of 882 patients had at least 1 rhythm intervention during follow-up, i.e. 155 patients (17.6%) underwent electrical cardioversion, 33 patients (3.7%) pharmacological cardioversion, and 77 patients (8.7%) catheter ablation for AF. Of the latter, 72 patients underwent a pulmonary vein isolation and 7 atrioventricular node ablation with pacemaker implantation. Furthermore, 14 patients (1.6%) underwent surgery for AF, 9 of which as stand-alone procedure and 5 concomitantly with another intervention, and 19 patients (2.2%) underwent an ablation for atrial flutter, 6 of which as stand-alone and 13 concomitantly with AF ablation.

Supplementary Fig. 1 shows the changes in treatment strategy for AF from baseline to follow-up. Relatively more patients changed from rate to rhythm control therapy than vice versa (24% vs 20%), although absolute numbers show the opposite (66 vs 99 patients). The majority of patients were on the same treatment strategy at baseline and at 1‑year follow-up, i.e. 610 of 775 patients (79%).

As in all registries, the strength of this registry is dependent upon the completeness of the data obtained by all participating centres, so clinical factors can be both over- and underrepresented. Furthermore, the reported data are observational. In order to reduce selection bias, participating centres were asked to include consecutive AF patients. Nonetheless, we believe the data presented in this article are comprehensive and provide a representative overview of AF patients in the Netherlands and Belgium and the treatment they receive.

Of note, patients were deemed underdosed for dabigatran only if both the regular and the lenient dose reduction criteria, i.e. age 75–80 years and eGFR 30–50 ml/min for which dose reduction can be considered, were not met. In addition, verapamil/diltiazem shared the same checkbox in the case report file, so it is unclear which of the two the patient is using, therefore we cannot be sure whether the dose reduction is adequate. Furthermore, treating physicians may have chosen to treat patients at increased risk of bleeding with the reduced dose of dabigatran, since the reduced dose is non-inferior to vitamin K antagonists (VKAs), this was not taken into account. For apixaban, the rate of underdosing is most likely to be overestimated, since in some patients not the daily dose of apixaban was filled in the case report file as requested, but rather the dose for a single gift. In patients with 10 mg and 2.5 mg of apixaban, it is clear whether the patient receives the reduced or full dose, for 5 mg however, this is not clear. These patients were assessed as having the reduced dose of apixaban, meaning that the rate of underdosing might be overestimated as these patients could in fact be on twice daily 5 mg of apixaban.