Strategic Clinical Networks and Senates
Yorkshire and the Humber
Yorkshire & the Humber Cardiovascular Strategic Clinical Network (South)
SYCOM Policy Statement
Non vitamin K antagonists for the prevention of stroke and transient ischaemic attack
(TIA) in patients with non–valvular atrial fibrillation (AF) at increased risk of stroke.
This paper represents the review of the initial NORCOM guidance for non-vitamin K
antagonists agreed in June 2012. It is in line with experience gained from the first 12 months
of using non vitamin K antagonists in non-valvular atrial fibrillation and the publication by
NICE of three guidelines relating to non-vitamin K antagonists available as alternatives to
warfarin to prevent stroke and TIA in patients with non–valvular AF (TA249 Dabigatran and
TA256 Rivaroxaban and TA275 Apixaban). This paper outlines the consensus from a
clinical advisory group formed to represent the relevant clinical specialties across the North
Trent Cardiac and Stroke Network catchment for the express purpose of advising on the
development of this treatment policy.
Patients with atrial fibrillation with a CHADS2 score of 1 or more (or equivalent annual
stroke risk ≥3%) should be offered an anticoagulant.
In a primary care setting the proactive identification of patients with non-valvular AF at
increased risk of stroke and not on an anticoagulant should be undertaken using audit tools
such as GRASP-AF or via the QOF register. Patients identified to be in this group should be
reviewed and the range of available options discussed. When deciding between agents
safety considerations should be paramount.
The non-vitamin K antagonists should be offered as an option as part of an informed
discussion.
Additional information is available to inform the discussion between doctor and patient.
However prescribers may wish to be mindful of the following: The non-vitamin K antagonists
are new drugs and do not have the long term safety record of warfarin; they are more
expensive than warfarin; they may however offer substantial benefits to those unable to take
warfarin.
The balance of risk and benefit may favour non-vitamin K antagonists for patients presenting
with TIA or minor stroke or stroke where rapid anticoagulation may further reduce the risk of
subsequent strokes.
Local formularies should decide the most appropriate Non -vitamin K antagonists for
use locally
Local decision makers are well placed to decide on the most appropriate agents to be used
locally, using factors for example evidence base for outcomes and side effects, relative costs
and experience of the agents.
South Yorkshire & Bassetlaw NOAC Policy FINAL 16.10.13
Patients who are well controlled on warfarin (defined by a lack of poor control, below)
should generally be maintained on warfarin.
NICE states that for people already taking warfarin the potential risks and benefits of
switching to a non-vitamin K antagonist should be considered in the light of their level of INR
control.
Patients who are currently prescribed warfarin with poor control, (defined as one INR
above 8, or 2 readings outside the range of 1.8 to 5 in a six month period) should be
considered for a non-vitamin K antagonist.
These are the levels defined by local haematologists that are considered to increase the risk
of bleeding or cardiovascular event to a degree where a change in agent would be
appropriate.
This approach will give wider access to for non-vitamin K antagonists and part of a
managed introduction of these agents, building on experience in the first year of use.
Increasing the access to these new drugs should enable more patients to be given
primary and secondary prevention and further reduce the incidence of stroke.
MHRA Guidance: For all the new oral anticoagulants the MHRA have issued guidance
drawing attention to the risk factors for bleeding, the need to pay attention to posology,
contraindications, and warnings and precautions for use to reduce the risk of bleeding.
Available at:
http://www.mhra.gov.uk/home/groups/plp/documents/drugsafetymessage/con321961.pdf
References
NICE Atrial fibrillation (CG36). Available at: http://guidance.nice.org.uk/CG36
NICE TA 249 Atrial fibrillation - dabigatran etexilate (TA249). Available at:
http://guidance.nice.org.uk/TA249
NICE TA256 Rivaroxaban for the prevention of stroke and systemic embolism in people with
atrial fibrillation. Available at: http://guidance.nice.org.uk/TA256
NICE TA275 Apixaban for preventing stroke and systemic embolism in people with
nonvalvular atrial fibrillation. Available at http://guidance.nice.org.uk/TA275
This document should be read in conjunction with prescribing information found in the British
National Formulary and Summary of Product Characteristics; prescribers should ensure
they have the relevant information found in these sources prior to prescribing for non-vitamin
K antagonists.
This guidance should be reviewed following material change in the evidence base for nonvitamin K antagonists in atrial fibrillation or associated NICE guidelines.
Richard Crosby
NHS South Yorkshire and Bassetlaw Commissioning Support Unit
On behalf of the SY&B Consensus Group of Clinical Specialists
8TH October 2013
South Yorkshire & Bassetlaw NOAC Policy FINAL 16.10.13
Appendix 1: Contra indications for warfarin and non vitamin K antagonists as specified in the summary of product characteristics (SPC)
for each drug.
Warfarin
o
o
o
o
o
o
Known
hypersensitivity to
warfarin or to any of
the excipients
Haemorrhagic stroke
Clinically significant
bleeding
Within 72 hours of
major surgery with
risk of severe
bleeding Within 48
hours postpartum
Pregnancy (first and
third trimesters)
Drugs where
interactions may lead
to a significantly
increased risk of
bleeding
Rivaroxaban
o
o
o
o
o
Hypersensitivity to the active substance or to
any of the excipients
Active clinically significant bleeding.
Lesion or condition, if considered to be a
significant risk for major bleeding. This may
include current or recent gastrointestinal
ulceration, presence of malignant neoplasms
at high risk of bleeding, recent brain or
spinal injury, recent brain, spinal or
ophthalmic surgery, recent intracranial
haemorrhage, known or suspected
oesophageal varices, arteriovenous
malformations, vascular aneurysms or major
intraspinal or intracerebral vascular
abnormalities.
Concomitant treatment with any other
anticoagulants e.g. unfractionated heparin
(UFH), low molecular weight heparins
(enoxaparin, dalteparin, etc.), heparin
derivatives (fondaparinux, etc.), oral
anticoagulants (warfarin, , dabigatran
etexilate, apixaban etc.) except under the
circumstances of switching therapy to or
from rivaroxaban or when UFH is given at
doses necessary to maintain an open central
venous or arterial catheter. Hepatic disease
associated with coagulopathy and clinically
relevant bleeding risk including cirrhotic
patients with Child Pugh B and C
Pregnancy and breast feeding
Dabigatran
o Hypersensitivity to the active substance or to any of
the excipients
o Patients with severe renal impairment (CrCL < 30
mL/min)
o Active clinically significant bleeding
o Lesion or condition, if considered a significant risk
factor for major bleeding. This may include current or
recent gastrointestinal ulceration, presence of
malignant neoplasms at high risk of bleeding, recent
brain or spinal injury, recent brain, spinal or
ophthalmic surgery, recent intracranial
haemorrhage, known or suspected oesophageal
varices, arteriovenous malformations, vascular
aneurysms or major intraspinal or intracerebral
vascular abnormalities
o Concomitant treatment with any other anticoagulants
e.g. unfractionated heparin (UFH), low molecular
weight heparins (enoxaparin, dalteparin etc), heparin
derivatives (fondaparinux etc), oral anticoagulants
(warfarin, rivaroxaban, apixaban etc) except under
the circumstances of switching therapy to or from
Pradaxa or when UFH is given at doses necessary
to maintain an open central venous or arterial
catheter
o Hepatic impairment or liver disease expected to
have any impact on survival
o Concomitant treatment with systemic ketoconazole,
cyclosporine, itraconazole, tacrolimus and
dronedarone
o Prosthetic heart valves requiring anticoagulant
treatment
Apixaban
o
o
o
o
o
Hypersensitivity to the active substance or to
any of the excipients
Active clinically significant bleeding.
Hepatic disease associated with
coagulopathy and clinically relevant bleeding
risk
Lesion or condition if considered a significant
risk factor for major bleeding. This may
include current or recent gastrointestinal
ulceration, presence of malignant neoplasms
at high risk of bleeding, recent brain or spinal
injury, recent brain, spinal or ophthalmic
surgery, recent intracranial haemorrhage,
known or suspected oesophageal varices,
arteriovenous malformations, vascular
aneurysms or major intraspinal or
intracerebral vascular abnormalities.
Concomitant treatment with any other
anticoagulant agent e.g. unfractionated
heparin (UFH), low molecular weight heparins
(enoxaparin, dalteparin, etc.), heparin
derivatives (fondaparinux, etc.), oral
anticoagulants (warfarin, rivaroxaban,
dabigatran, etc.) except under the
circumstances of switching therapy to or from
apixaban or when UFH is given at doses
necessary to maintain an open central
venous or arterial catheter
*http://www.gpnotebook.co.uk/simplepage.cfm?ID=x20030129224615665170
This table should be read in conjunction with the SPC for each drug available at http://www.medicines.org.uk/EMC/default.aspx
Clinicians should use their clinical judgement where cautions rather than contraindications are listed in the SPC as to the risks vs. the benefits of
starting a particular and ensuring appropriate monitoring is carried out if required.
South Yorkshire & Bassetlaw NOAC Policy FINAL 16.10.13