Predictors, time course, and outcomes of persistence patterns in oral anticoagulation for non-valvular atrial fibrillation: a Dutch Nationwide Cohort Study

Abstract

Aims Persistence with direct oral anticoagulants (DOACs) has become a concern in non-valvular atrial fibrillation (NVAF) patients, but whether this affects prognosis is rarely studied. We investigated the persistence with oral anticoagulants (OACs) and its association with prognosis among a nationwide cohort of NVAF patients. Methods and results DOAC-naive NVAF patients who started to use DOACs for ischaemic stroke prevention between 2013 and 2018 were included using Dutch national statistics. Persistence with OACs was determined based on the presence of a 100-day gap between the last prescription and the end of study period. In 93 048 patients, 75.7% had a baseline CHA2DS2-VASc score of ≥2. The cumulative incidence of persistence with OACs was 88.1% [95% confidence interval (CI) 87.9–88.3%], 82.6% (95% CI 82.3–82.9%), 77.7% (95% CI 77.3–78.1%), and 72.0% (95% CI 71.5–72.5%) at 1, 2, 3, and 4 years after receiving DOACs, respectively. Baseline characteristics associated with better persistence with OACs included female sex, age range 65–74 years, permanent atrial fibrillation, previous exposure to vitamin K antagonists, stroke history (including transient ischaemic attack), and a CHA2DS2-VASc score ≥2. Non-persistence with OACs was associated with an increased risk of the composite outcome of ischaemic stroke and ischaemic stroke-related death [adjusted hazard ratio (aHR) 1.79, 95% CI 1.49–2.15] and ischaemic stroke (aHR 1.58, 95% CI 1.29–1.93) compared with being persistent with OACs. Conclusion At least a quarter of NVAF patients were non-persistent with OACs within 4 years, which was associated with poor efficacy of ischaemic stroke prevention. The identified baseline characteristics may help identify patients at risk of non-persistence.

Oral anti‐coagulant treatment patterns in atrial fibrillation patients diagnosed with cancer: A Danish nationwide cohort study

“…Adherence and persistence with OAC is vital for achieving a clinical benefit of stroke prophylaxis. 10,25,26 Monitoring warfarin therapy allows for some treatment control related to continuous dose adjustments, but suboptimal adherence has been reported in one third of all AF Note: Data present the % (number of patients) or the median (interquartile range), as indicated.…”

“…Monitoring warfarin therapy allows for some treatment control related to continuous dose adjustments, but suboptimal adherence has been reported in one third of all AF patients 27,28 . Although DOAC treatment does not require routine monitoring, some studies dispute that patients treated with DOAC should be prone to non‐adherence in daily clinical practice, 16,29 whereas others have found that one in four patients did not persist with recommended DOAC therapy over four years, 10,22 None of these studies focused on OAC treatment patterns in patients with incident cancer, and comparison of persistence across studies are challenged by methodological differences. Our estimated one‐year incidence of DOAC discontinuation of 26% is lower than reported in a previous meta‐analysis showing persistence at 62%; however, this was not focused on patients with cancer 30 .…”

“…There has been a rapid uptake of the direct oral anti‐coagulants (DOACs) apixaban, dabigatran, rivaroxaban and edoxaban at the expense of vitamin K antagonists (VKA) for stroke prevention 6 and randomized controlled trials and cohort studies have demonstrated non‐inferiority of DOACs for prevention of ischaemic stroke and superior safety with lower bleeding risk compared with VKA 7,8 . Adherence and persistence with OAC therapy in patients with AF in general may be suboptimal in at least one in five patients initiating VKA, 9 and it was recently demonstrated that one in four patients do not persist with recommended therapy over four years after initial DOAC prescription 10 …”

“…[12][13][14][15] On the other hand, patients with more than one chronic condition may have a higher degree of persistence than those without multiple chronic disease. 10,16 Importantly, none of these studies have examined whether an incident cancer diagnosis influences persistence with OAC therapy.…”

Switching from vitamin K antagonists to direct oral anticoagulants in non‐valvular atrial fibrillation patients: Does low time in therapeutic range affect persistence?

“…The lack of monitoring, however, may contribute to suboptimal treatment persistence to DOACs, which was identified by several observational studies. [11][12][13][14] Although NVAF patients who receive VKAs but with a low TTR are suggested to switch to a DOAC, 2 it is unknown whether the switch improves the persistence to oral anticoagulation. This question is relevant because non-persistence to OAC was associated with an increased risk of ischemic stroke in DOAC users.…”