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NOACs: Overview

Table 4: Summary of the main current guidelines on antithrombotic therapy in patients with non-valvular atrial fibrillation Guidelines

Year ACCP 10th edition

ESC (update pending) JCS

CCS update AHA/ACC/

HRS (update pending) NICE

2012 CHA2DS2 2014 CHADS2

2014 CHADS2 2014 CHA2DS2

2014 CHA2DS2 VASc

Yes (≥1) Yes (≥1)


Yes (≥1) Yes (≥2)


Yes (choice depends on CHADS2

) Yes Yes (in pts unable to take W) Yes (≥2 or ≥1 in men) No



= 0 + age < 65 + CAD/PAD VASc = 1 (or no therapy, or OAC)

Not recommended

ACC: American College of Cardiology; ACCP: American College of Chest Physicians; AHA, American Heart Association; CCS: Canadian Cardiovascular Society; ESC: European Society of Cardiology; HRS, Heart Rhythm Society; JCS: Japanese Circulation Society; NICE: National Institute for Health and Care Excellence; CAD: coronary artery disease; NOAC: non-Vitamin K oral anticoagulant; OAC: oral anticoagulant; PAD: peripheral artery disease; TE: thromboembolism

ranging study24 that dabigatran at least,

and probably other NOACs are unsuitable anticoagulants for patients recently fitted with mechanical prosthetic heart valves, but long-term anticoagulant management of such patients is not clear. It may be that NOACs should also be avoided in the early period following bioprosthetic valve implantation, but long-term anticoagulation is usually not needed specifically because of the valve and the choice of anticoagulant should be related to the AF indication. There are several other relatively high-risk situations where the need for anticoagulation may not merely depend on the presence of AF; for example, rheumatic mitral stenosis and hypertrophic cardiomyopathy.25

It is

likely that NOAC treatment will suffice in these patients but no data are yet available.


Because all the NOACs depend in part on renal elimination, they are contraindicated or not recommended in patients with severe renal impairment (creatinine clearance (CrCl) <30ml/min or < 15ml/min depending on the individual agent) and when appropriate, lower doses should be used when CrCl is between 30 and 50ml/min. In the US, based on modelling data, dabigatran 75mg BID can be used when CrCl is between 15 and 30ml/min and apixaban 5mg BID can be applied in patients maintained on haemodialysis. Patients with AF may develop acute coronary syndrome or unstable angina and, conversely, patients with unstable coronary disease may develop AF. In these situations, both anticoagulation is indicated for stroke prevention and dual antiplatelet therapy is needed to prevent

in-stent thrombosis. However, this triple therapy inevitably increases the risk of bleeding substantially. In principle, the length of triple therapy is reduced to little more than a month in patients with a high bleeding risk and single antiplatelet therapy is combined with a VKA anticoagulant for the remainder of the first year before dropping the antiplatelet therapy completely and continuing only with the anticoagulant when the coronary disease is stable but AF thrombo- prophylaxis is still required.26

In this

setting there are currently no controlled data relating to the use of NOAC therapy whereas there is considerable clinical experience with VKA drugs. Some physicians prefer VKA therapy for the intermediate term; others are concerned about the dangers of converting patient from NOAC treatment to VKA therapy because of the possibility of periods of under-anticoagulation. Good quality controlled data will soon be available. The lack of direct NOAC antidotes was a concern for some physicians and patients. Although Phase III clinical trials were very successfully concluded without such drugs, the recent announcements relating to rapid and highly effective antidotes will provide reassurance.27,28 Praxbind, the first specific NOAC

reversal agent, received EMA approval in November 2015 based on healthy volunteer data and an interim analysis of the RE-VERSE AD trial with dabigatran patients.28–30


Many national and international guidelines now advocate the use a risk scoring scheme, such as CHA2DS2-VASc (or a similar variation) to identify those

patients who are at a stroke risk of less than approximately 1% per annum and therefore unable to benefit (in net terms) from anticoagulant therapy.31–33

If OAC cannot be used Not recommended

Risk stratification 2016 CHADS2

OAC indicated (according to the risk score)

Yes (≥1) NOAC preferred Yes Role of aspirin CHADS2 = 0 if pt prefers treatment

For these

patients, no antithrombotic of any sort, including antiplatelet therapy, is recommended for stroke prevention. The remaining patients are offered anticoagulant treatment unless there is a very high risk of bleeding that cannot be reduced by prudent management, when a mechanical solution, such as left atrial appendage occlusion, may be preferred. Most international guidelines now make a recommendation preferring NOAC to VKA therapy,33–36

but some remain equivocal31,32 (Table 4). For most patients

and clinicians, the substantially lower risk of intracranial haemorrhage associated with NOAC therapy clinches the decision in favour of NOAC treatment.


Anticoagulant therapy is outstandingly effective in reducing the stroke rate in at-risk patients with AF, but the inevitable increased risk of bleeding, together with the complexity of managing VKA therapy management has deterred many doctors and patients from widespread adoption of this treatment. The recent development of non-VKA anticoagulants with predictable pharmacokinetics, no food–drug interactions and few drug–drug interactions, which are either superior or non-inferior to warfarin in terms of efficacy and safety as documented in large, well-designed, randomised, controlled trials is leading to a major change. As these drugs are progressively accepted into clinical practice, more

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