Updated ‘Practical Guide’ to the NOACs
What’s New (and Industry Can’t Tell You)
C
urrent guidelines for managing patients
with nonvalvular AF mainly discuss
the indications for anticoagulation in
general (e.g., based on the CHA2DS2-VASc score
and bleeding risk). They broadly cover vitamin
K antagonists (VKAs) as well as the use of the
non-vitamin K antagonist oral anticoagulants,
but these documents offer less guidance on how
to deal with new oral anticoagulants (NOACs) in
specific clinical situations. Recently, the European
Society of Cardiology (ESC) and European Heart
Rhythm Association (EHRA) published a practical guide on the use of the NOACs.1
The document was thought to be necessary in
order to better summarize existing information
on different drugs, to answer clinical questions
that fall outside of what drug companies can
legally answer, and to make distinctions between
the different drugs.
This is the second time the EHRA has been
involved in the development of such a document.2
The first document was featured in the June 2013
CardioSource WorldNews: “ESC Guide to New Oral
Anticoagulants When industry can’t legally tell
you, it’s up to societies to offer clinical guidance.”
According to Hein Heidbuchel, MD, PhD, a
professor at the University of Leuven, Belgium,
secretary of the EHRA, and first author of both
of the guides, “I felt a tremendous need among
colleagues on how to deal with practical situations in patients treated with NOACs.” Moreover,
he said, the numerous new drugs on the market
make it challenging. Given the different package
inserts, which he noted are largely analogous but
differ in some important aspects, “there was a
risk of a chaos of information.”
The new guide was co-authored by A. John
Camm, MD (St. George’s University, London,
UK), first author of the ESC AF guidelines.3 Dr.
Heidbuchel explained the importance of the NOACs guide by distinguishing between guidelines
(“when to use a drug or intervention”) and guidance (“how to use them properly”).
ADDRESSING IMPORTANT ISSUES
The practical guide covers 15 topics of concrete
clinical scenarios for which practical answers
have been formulated, based on available evidence. Topics covered include:
• how to initiate and monitor the NOACs
• how to measure their anticoagulant effect (if
needed) in specific situations
• switching between anticoagulants
• managing patients who require surgical intervention or ablation
• patients with chronic kidney disease
• management of bleeding complications.
ACC.org/CSWN
The guide also addresses adherence-related
issues. While the new drugs remove the need
for regular monitoring of anticoagulation level
necessary with the VKAs, Dr. Heidbuchel said,
“Compliance is very important for the novel anticoagulant drugs because they have a very short
half-life. That means that if you don’t take them
you will not be protected by anticoagulation and
are at greater risk of thromboembolic events.”
In an effort to improve adherence, the document includes a universal patient education card.
The issue is also addressed with a pre-specified
follow up scheme.
Addressing drug-drug interactions, the document shows the effect (if any) of 14 specific
drugs or drug classes on anticoagulant plasma
levels (per area under the curve or AUC) for
each new agent. The drug-drug interactions and
recommendations for new oral anticoagulant dosing include atorvastatin, verapamil, antacids, the
azole antifungals, and HIV protease inhibitors.
For example:
• In the case of atorvastatin, dabigatran AUC
increased by 18%, with no data yet for
apixaban, and no effect seen when used with
edoxaban or rivaroxaban.
• The effect of verapamil on AUC of the new
agents varies: for dabigatran, the increase
reported ranged from 12%–180%, with the
ESC/EHRA guide suggesting a reduced dose
of dabigatran and that the drugs be taken
simultaneously. For edoxaban, a 53% increase
in AUC lead to the recommendation to reduce the new oral anticoagulant dose by 50%
when used in patients on verapamil. Limited
data demonstrate only a minor interaction of
verapamil and rivaroxaban thus far, although
the guide recommends using the combination
with caution if creatinine clearance is 15–50
ml/min. Because detailed information is not
available yet for apixaban or rivaroxaban, the
authors state it is prudent to abstain from
using these two agents in combination with
verapamil until more information is available.
The guide also summarizes key data on the
use of NOACs in the setting of ACS, PCI, or
stable CAD plus atrial fibrillation. The document
urges that measures to reduce bleeding risk in patients with ACS should be retained: low doses of
aspirin (75–100 mg), especially when combined
with a P2Y12 inhibitor; new-generation DES or
bare-metal stents (BMSs) to minimize the duration of triple therapy; and a radial approach for
interventional procedures (reducing at least the
risk of access site bleeding).
For patients who have had elective PCI, the
authors propose a default time of triple therapy
of 1 month (for a BMS or newer DES), thereafter
stepping down to dual therapy (with OAC and
either aspirin or clopidogrel) until 1 year, then
monotherapy thereafter.
In patients after an ACS, treated medically or
with PCI, the practical guide suggests a default
strategy of 6 months of triple therapy before
stepping down to double therapy. In those wi F