Comparison between Direct Oral Anticoagulation (DOAC) Interruption and DOAC Continuation in Patients Undergoing Elective Invasive Coronary Angiography or Percutaneous Coronary Intervention

Patients with atrial fibrillation (AF) often have coexisting coronary artery
disease (CAD). The prevalence of CAD in patients with AF ranges from 17 to
46.5%. An estimated 5 to 15% of all AF patients will require coronary stenting
and therefore will receive antiplatelet therapy in addition to Vitamin K
Antagonists (VKA) or Direct Oral Anticoagulants (DOAC) (2). In patients using
VKA it is recommended to defer elective coronary angiography until INR is <1.8
when femoral artery access is used, or <2.2 when radial artery access is used
(3). However, in a meta-analysis conducted by Kowalewski et al., no significant
differences of periprocedural bleeding risk between interrupted or
uninterrupted VKA use (4). In addition, DOACs are more commonly used in
preventing thromboembolic complications in patients with AF, thereby
substituting VKA use. This shift in antiocoagulant use, opposes a challenge in
managing ischemic and bleeding complications in invasive coronary angiograqphy
(ICA) and percutaneous coronary interventions (PCI).

Patients using DOAC and undergoing ICA or PCI may have an increased risk of
bleeding complications. Therefore, it is recommended to discontinue DOAC at
least 12 to 48 hours in advance of ICA or PCI, depending on renal function and
the particular DOAC regimen (5). In order to reduce bleeding risk, it is
preferred to use radial access instead of femoral access. Multiple studies show
a higher risk of bleeding complications when femoral access is used (6-8). In
contrast to periprocedural VKA use, only limited articles are available
regarding uninterrupted use of DOAC during ICA or PCI. In 2019 Chongprasertpon
et al. found no significant differences between interrupted and uninterrupted
DOAC in elective ICA or PCI (1). However, an important limitation of this study
is the limited amount of participants and the fact that no significant
bleedings were found in both groups of 49 patients.

To our knowledge, no large population studies have focused on periprocedural
continuation of DOAC therapy in patients diagnosed with chronic coronary
syndrome (CCS) and undergoing elective ICA or PCI. Clinical decisions on DOAC
use must therefore be based on clinical trials in which substantial numbers of
patients with acute coronary syndrome (ACS) were included. Radial artery access
is preferred along with intraprocedural unfractionated heparin either at a
standard dose (70-100 U/kg) or, in those with uninterrupted VKA, at a lower
dose of 30-50 U/kg (5). The ESC guidelines for the management of ACS in
patients presenting with NSTEMI (2020) state that UFH at a dose of 60 IU/kg
should be administered in patients with DOAC usage (9). Pre-treatment with
aspirin 75-100 mg daily is recommended, and clopidogrel (300-600 mg loading
dose if not on long-term maintenance therapy) is recommended in preference to
prasugrel or ticagrelor (5).

In addition, a recent report from the National Cardiovascular Data Registry
(NCDR) Acute Coronary Treatment and Intervention Outcomes Network Registry
(ACTION-registry) which included more than 26.000 patients showed that DOAC
therapy was not associated with an increased risk of in-hospital bleeding.
However, no information was given concerning periprocedural DOAC use in this
study (6).

In clinical practice, it is commonly seen that patients or physicians forget to
temporarily discontinue DOAC therapy, prior to an elective procedure. This
forms a practical problem in daily care, assumingly raising both costs and time
needed in preparation for an elective procedure. In this prospective study, we
aim to examine the safety of DOAC continuation in patients who undergo ICA or
PCI in both elective and emergency procedures.

The aim of our study is to study the safety of continued DOAC use during ICA or
CAG in elective procedures, by comparing the risk of in-hospital and 30-day
bleeding complications between continued and interrupted DOAC use.

Eligible patients will be randomized to DOAC continuation or interruption at
the moment when ICA or PCI is planned. After randomisation the patient will be
instructed either to continue DOAC use as usual or to stop DOAC 24 hours in
advance of the procedure. Treatment will be assigned on the basis of a 1:1
ratio.

Interruption of pre-procedural DOAC use is mainly based on expert opinion (15).
Clearance of DOACs is predominantly renal. Therefore, timing of DOAC
interruption depends on renal clearance of a patient. Clearance must be
measured at least 3 months prior to the procedure. Figure 2 shows an overview
of DOAC interruption, varying for each DOAC and creatinine clearance.

Stopping DOAC 24 hours prior to the procedure implies that there must be at
least 24 hours between intake of the last dose of DOAC and start of the
procedure.

Group 2 (intervention): DOAC continuation
In group 2, all patients will continue to use their specific DOAC as usual.
This means that no adjustments of DOAC use will be made before and after ICA or
PCI. After the procedure patients will continue to use DOAC from the next
planned dose.

Based on earlier research on VKAs, no significant bleeding complications were
seen comparing bleeding rates in patiënts with uninterrupted versus interrupted
VKA use. Furthermore Chongpraserton et al. showed no significant
bleedingcomplications in a population of 98 patients on DOAC, undergoing
elective ICA or PCI. Half of this population continued DOAC use and the other
group shortly interrupted DOAC periprocedural.

Based on these findings, no risk differences are expected between the two
groups. If any difference in risk will be present, this must be only a small
risk, based on the low number of bleedingcomplications that were seen in
earlier studies.