INFOGRAPHIC

INFOGRAPHIC

SLOW RISE OF NOACs

NEW ORAL ANTICOAGULANTS FOR STROKE

PREVENTION IN ATRIAL FIBRILLATION

Warfarin usage in 2015: 11,551,000

Prescription items dispensed in the community in England. Edoxaban was approved in 2015.
Rivaroxaban
Dabigatran
Apixaban

1,538,000
The National Institute for Health and Care Excellence recommends NOACs as an option for
non-valvular AF after a discussion about the risks and benefits compared with warfarin

1,000,000

European Society of Cardiology guidance recommends that

NOACs are broadly preferable to warfarin for non-valvular AF

Around 12,500 strokes are caused by atrial fibrillation (AF) in the UK each year,
and 7,100 of these are preventable with appropriate anticoagulation. Four new oral
anticoagulants (NOACs) are now available in the UK in addition to warfarin.

667,000
500,000

366,000
2012

2013

2014

2015

ANTICOAGULANT EFFECT OF NOACs

The coagulation cascade is a series of reactions involving coagulation factors that ultimately results in the formation of a blood clot. The
NOACs directly inhibit one specific coagulation factor in the cascade, whereas warfarin prevents the coagulation process by suppressing
the synthesis of several vitamin K-dependent coagulation factors.

INTRINSIC (CONTACT ACTIVATION) PATHWAY

EXTRINSIC (TISSUE FACTOR) PATHWAY

Activated by contact of the vessel wall with

lipoprotein particles or bacteria

Activated in response to tissue injury

Factors IX

Factors XI, XII

Factor VII

Factor X

Factor Xa

RIVAROXABAN
EDOXABAN
Thrombin (Factor IIa)

WARFARIN

Fibrinogen
(Factor I)

Usual dose: 110mg od. Bioavailability: 99%.

Peak plasma level: 7296 hrs. Half-life: 2060 hrs.
Renal excretion: <1%. Liver metabolism: yes.
Drug-drug and drug-food interactions: numerous.

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1.60%

DABIGATRAN

Fibrin
(Factor Ia)

RATE OF PRIMARY
OUTCOME/YEAR:

1.18%

1.50%

THE NOACs

All NOACs are indicated for the prevention of stroke and systemic embolism in adults with nonvalvular AF who have one or more risk factors, such as
prior stroke or transient ischaemic attack; age 75 years; hypertension; diabetes mellitus and symptomatic heart failure. Unlike warfarin, the NOACs
have a predictable therapeutic response, rapid onset of action, few drug interactions and no requirement for regular coagulation monitoring.

DABIGATRAN ETEXILATE
(PRADAXA; BOEHRINGER INGELHEIM)

Usual dose: 20mg od with food. Bioavailability:

66% (without food), almost 100% (with food). Peak
plasma level: 24 hrs. Half-life: 59 hrs (young), 1113 hrs
(elderly). Renal excretion: 35%. Liver metabolism: yes.

Usual dose: 150mg bid. Bioavailability: 37%.

Peak plasma level: 2hrs. Half-life: 1217hrs.
Renal excretion: 80%. Liver metabolism: no.

Interactions: Use with strong inhibitors of both CYP3A4 and

P-gp, such as azole-antimycotics or HIV protease inhibitors, is
not recommended. Co-administration with dronedarone and
strong CYP3A4 inducers should be avoided.

Interactions: Use with strong P-gp inhibitors ketoconazole,

cyclosporine, itraconazole and dronedarone is contraindicated.
Use with P-gp inhibitor verapamil requires dose reduction.
Use with P-gp inducers should be avoided.

APIXABAN
(ELIQUIS; BRISTOL-MYERS SQUIBB-PFIZER)

EDOXABAN (LIXIANA; DAIICHI SANKYO UK)

Usual dose: 5mg bid. Bioavailability: 50%.

Peak plasma level: 14 hrs. Half-life: 12 hrs.
Renal excretion: 27%. Liver metabolism: yes.
Interactions: Use with strong inhibitors of CYP3A4 or
P-glycoprotein (P-gp) is not recommended. Use with
strong inducers of CYP3A4 and P-gp requires caution.

Usual dose: 60 mg od. Bioavailability: 62%. Peak

plasma level: 12 hrs. Half-life: 1014 hrs. Renal
excretion: 50%. Liver metabolism: minimal.
Interactions: Use with the P-gp inhibitors ciclosporin,
dronedarone, erythromycin or ketoconazole requires
dose reduction to 30mg once daily. Use with caution
concomitantly with P-gp inducers (e.g. rifampicin).

DECIDING WHICH NOAC

Several patient characteristics may be considered when deciding on which NOAC to recommend. Patient preference for once daily dosing may also
be taken into account. CAD: coronary artery disease, MI: myocardial infarction, ACS: acute coronary syndrome.

Sources: Slow rise of NOACs NHS Digital; European Heart Journal; NICE; Timeline New England Journal of Medicine;
The NOACs Europace; Summaries of product characteristics; Deciding which NOAC Arrhythmia & Electrophysiology Review.
Editorial adviser: Satinder Bhandal, consultant anticoagulation pharmacist, Buckinghamshire Hospitals Trust
Infographic: MAG

152

1.27%

2015

ENGAGE-AF is published in NEJM

showing edoxaban is noninferior to
warfarin with respect to the prevention
of stroke or systemic embolism and is
associated with significantly lower rates
of bleeding and death from cardiovascular
causes. GI bleeding increased with the
60mg dose of edoxaban.

RATE OF PRIMARY
OUTCOME/YEAR:

APIXABAN

WARFARIN

Prothrombin (Factor II)

2014

RIVAROXABAN (XARELTO; BAYER)

Tissue factor

Factor X

2013
ARISTOTLE trial is published in
NEJM showing apixaban is superior to
warfarin in preventing stroke or systemic
embolism in patients with AF and results
in lower mortality. Patients treated
with apixaban had significantly fewer
intracranial bleeds, but GI bleedings
were similar between both groups.

Idarucizumab (Praxbind), an
antidote to dabigatran

EDOXABAN

Edoxaban

2.4%

2.1%

APIXABAN

Warfarin

RATE OF PRIMARY
OUTCOME/YEAR:

Warfarin

1.69%
1.11%

2012

ROCKET AF trial is published in NEJM

showing rivaroxaban is non-inferior to
warfarin for the prevention of stroke or
systemic embolism, with no differences
in the risk of major bleeding, although
intracranial and fatal bleeding occurred
less frequently in the rivaroxaban group.
GI bleeding was greater with rivaroxaban.

RATE OF PRIMARY
OUTCOME/YEAR:

Warfarin

RE-LY trial is published in NEJM

showing that dabigatran 150mg
BID is superior to warfarin for
prevention of stroke and systemic
embolism, with no significant
differences in major bleeding,
although gastrointestinal (GI)
bleeding was higher.

2011

Rivaroxaban

2010

Dabigatran

APPROVAL IN EU
DRUG TRIALS &
RATE OF STROKE
OR SYSTEMIC
EMBOLISM
(PRIMARY
OUTCOME)

RIVAROXABAN

Apixaban

DABIGATRAN

Warfarin

2011

DAWN CONNELLY

2009

1,500,000

SEPTEMBER 2016

Cross-linked
Fibrin clot

PREVIOUS, OR HIGH RISK OF,

GI BLEED

HIGH ISCHAEMIC STROKE RISK, LOW

BLEEDING RISK

CAD, PREVIOUS MI OR HIGH RISK

FOR ACS/MI

SEPTEMBER 2016

RENAL
IMPAIRMENT

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DIARRHOEA
DISORDERS

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