Practice Update: Cardiology

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3-Day Interruption of
Direct Oral Anticoagulants
Appropriate for
Most Procedures
European Heart Journal
Take-home message
• This prospective study (N = 422) evaluated the predictors of direct oral anticoagulant
concentrations and strategies to minimize bleeding prior to invasive procedures.
The results revealed that renal function, duration of discontinuation prior to the
procedure, antiarrhythmic treatment, and high-risk bleeding procedures were
associated with higher periprocedural bleeding events. The direct oral anticoagu-
lant (DOAC) assay was more effective in predicting bleeding events than standard
hemostasis assays.
• The authors concluded that a 3-day preprocedure discontinuation of DOACs will
minimize the anticoagulant effect for most patients; however, patients with renal
impairment or those receiving antiarrhythmic treatment will require a longer duration
of discontinuation.
Abstract
AIMS Patients receiving direct oral anticoagulants
(DOACs) frequently undergo elective invasive
procedures. Their management is challenging.
We aimed to determine the optimal duration of
DOAC discontinuation that ensures a minimal
anticoagulant effect during the procedure.
METHODS AND RESULTS This prospective multicen-
tre study included 422 DOAC-treated patients
requiring an invasive procedure. Pre-proce-
dural DOAC concentration ([DOAC]) and routine
haemostasis assays were performed to deter-
mine i/the proportion of patients who achieved
a minimal pre-procedural [DOAC] (≤30ng/mL)
according to the duration of DOAC discontin-
uation, ii/the predictors of minimal [DOAC] and,
iii/the ability of routine assays to predict mini-
mal [DOAC]. Lastly, we assessed the predictors
of peri-procedural bleeding events. The dura-
tion of DOAC discontinuation ranged from 1 to
218 h and pre-procedural [DOAC] from≤30 to
527ng/mL. After a 49–72-h discontinuation, 95%
of the [DOAC] were≤30ng/mL. A 72-h discontin-
uation predicted concentrations≤30ng/mL with
91% specificity. In multivariable analysis, duration
of DOAC discontinuation, creatinine clearance
<50mL/min and antiarrhythmics were independ-
ent predictors of minimal pre-procedural [DOAC]
(concordance statistic 0.869; 95% confidence
interval: 0.829–0.912). Conversely, routine hae-
mostasis assays were poor predictors. Last,
creatinine clearance <50mL/min, antiplatelets
and high-bleeding risk procedures were pre-
dictors of bleeding events.
CONCLUSION A last DOAC intake 3 days before
a procedure resulted in minimal pre-proce-
dural anticoagulant effect for almost all patients.
Moderate renal impairment, especially in dab-
igatran-treated patients, and antiarrhythmics in
anti-Xa-treated patients should result in a longer
DOAC interruption. In situations requiring test-
ing, routine assays should not replace DOAC
concentration measurement.
Predictors of pre-procedural concentrations of
direct oral anticoagulants: a prospective mul-
ticentre study. Eur Heart J 2017 Jul 24;[EPub
Ahead of Print], A Godier, A-S Dincq, A-C Mar-
tin, et al.
COMMENT
By Amish N Raval MD
The direct oral anticoagulants
(DOACs) have emerged as alterna-
tives to warfarin for the prevention
and treatment of thromboembolic dis-
ease. DOACs are appealing because they
have a more predictable pharmacoki-
netic profile and have fewer food–drug
and drug–drug interactions than warfa-
rin. Despite their widespread use, most
clinicians remain apprehensive about
managing DOACs in the periprocedural
setting. In the United States, the absence
of FDA-approved assays to directly meas-
ure DOAC concentration and antidotes for
the factor Xa inhibitors have contributed
to these concerns.
Godier et al sheds light on this issue by
demonstrating that DOAC concentration
predictably drops to almost undetectable
(<30 ng/dL) levels after 72 hours of cessa-
tion in a prospective real-world registry of
patients who are on DOACs and require
an assortment of elective procedures.
This observation will undoubtedly assist
investigators in designing future DOAC
interruption protocols. Managing DOACs
in the periprocedural setting requires an
understanding of a patient’s thromboem-
bolic risk and bleeding risk. Contributing
to these two risks include variables such
as age, gender, frailty, renal function,
coexisting antithrombotic medications,
bleeding risk associated with the proce-
dure being planned, and postoperative
sequelae such as prolonged bedrest or
re-operations. Until we have more pro-
spectively acquired data such as that
provided by Godier et al, healthcare sys-
tems are strongly encouraged to develop
periprocedural DOAC interruption proto-
cols with multidisciplinary input.
Dr Raval is Associate
Professor of Medicine,
Director: Cardiovascular
Clinical Research, University
of Wisconsin School of
Medicine and Public Health,
Madison, Wisconsin.
ARRHYTHMIAS/HEART RHYTHM DISORDERS 23
VOL. 2 • NO. 2 • 2017