Introduction
Arterial and venous thromboembolic conditions are estimated to account
for 1 in 4 deaths worldwide in 2010 and are a leading cause of mortality
[1]. As atrial fibrillation (AF) (with a prevalence of 1-3% in
Europe) is associated with an estimated fivefold rise in ischemic stroke
risk, it is a major contributor to arterial thrombosis. [2].
Diagnosed in 1-2 per 1000 persons per year venous thromboembolism (VTE)
including both deep vein thrombosis (DVT) and pulmonary embolism (PE) is
the third most common cardiovascular disorder after acute coronary
syndrome and ischemic stroke [3].
Given the impact of ischemic stroke and VTE, adequate pharmacotherapy to
reduce the incidence and burden of ischemic stroke and VTE is essential.
Both direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs)
are highly effective in stroke prevention (relative risk reduction
≈64%) and prevention of venous thrombotic events (relative risk
reduction ≈80%) [3]. In most clinical guidelines DOACs are
preferred over VKAs due to their simpler fixed dose regime, no need for
international normalised ratio (INR) monitoring and fewer intracranial
bleedings. Medication adherence is, however, a prerequisite for optimal
protection against thromboembolic complications [4]. Paradoxically,
no need for INR monitoring for DOACs also means no monitoring of
adherence as the INR can be seen as a surrogate marker for proper VKA
use [5].
Recent studies have shown that medication adherence and persistence
cannot be taken for granted for patients on DOACs. Various studies
demonstrated that either the implementation adherence (defined as the
extent to which a patient’s actual dosing corresponds to the prescribed
dosing regimen, from initiation until the last dose) and medication
persistence (defined as unjustified discontinuation of the drug) is
suboptimal. An international study by Banerjee et al. showed that
adherence to DOACs does not exceed 55.2% [5], while according to a
Dutch follow-up study by Zielinski et al. the non-persistence after 1
year of follow-up was 34% [6]. In an observational study conducted
in a primary care setting Capiau et al. found that half of the study
population did not take their DOAC (mainly non-intentional) on at least
17 cumulative days per year and that 21% were non-adherent [7].
Ruff et al. estimated long-term adherence for DOACs to be only in the
40-60% range [8]. One of the findings from the Switching Study
conducted by Bartoli-Abdou et al. was that after switching from VKA to
DOAC 39% of patients had sub-optimal adherence measured by self-report
[9].
In contrast, a study by Toorop et al. found a clearly higher
self-reported adherence of 86% [10]. In a meta-analysis by Ozaki et
al. it was calculated that the percentage of patients with good
adherence is 69% [11]. Another important finding in this study was
that reduced adherence was associated with poorer clinical outcomes.
Medication adherence and persistence are influenced by different factors
like medication beliefs, treatment knowledge, patient’s self-efficacy
and also side effects. For example, a study by Rolfes et al. concluded
that 9% of DOAC users stopped their DOAC therapy because of side
effects [12,13]. Minor bleeding is according to Toorop et al. an
important predictor for non-persistence [10]. Mitrovic et al. have
also shown that minor bleeds are common among DOAC users and are
associated with discontinuation, although no associations were found
between minor bleeds and non-adherence, lack of trust or concerns.
However, they showed that on an individual basis, there were patients
that reported a high burden of minor bleeds [14,15,16]. Despite
two-thirds of DOAC users in the aforementioned study by Capiau et al.
reported side effects (with easy bleeding (40.2%) being the most common
for all DOACs), there was an overall positive attitude towards DOAC use
[7]. Bartoli-Abdou et al. found that believing that medications in
general were overused in healthcare at baseline and that increasing
concerns about anticoagulation over time while also having doubts
concerning the necessity of the drug treatment were both associated with
lower self-reported adherence [9].
Given the variation between adherence estimates found in the literature,
inconclusive findings regarding the role of side effects, their burden
and ambiguity regarding the role of specific personal beliefs that can
impede good adherence, this study aims to assess implementation
adherence among DOAC users and associations between beliefs about
medication, perceived side effects, their burden and implementation
adherence.