REVISED Anticoagulation module 3: anticoagulant therapy

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Which drug to choose for stroke prevention?

Based on this data, all four NOACs are now approved by NICE as an option for stroke prevention within their licensed indications (i.e. non-valvular AF with one or more risk factors for stroke). Given their equivalent or superior efficacy, with apparently superior safety, ESC guidelines advise choosing a NOAC first line, in the absence of contraindication (see figure 8). NICE have suggested that a NOAC might be preferred if a patient’s time in therapeutic range on warfarin is <65%.

Trial data will only be a part of the decision-making process. Patients should be involved; some will not wish to switch, or be nervous of new medications. Financial considerations will also play a part. In the UK, some Clinical Commissioning Groups (CCGs) have sought to limit use of NOACs to reduce cost.25 While NOACs are considerably more expensive than warfarin, it is likely that this cost will be at least partially offset by the improved efficacy and safety (with consequently reduced costs of stroke care/management of bleeding), and by reduced monitoring costs. NICE have undertaken a number of costing analyses:

Economic analyses have also been undertaken in other healthcare settings.26 NOACs have not been directly compared in head-to-head trials, and direct comparison between trials is difficult, as the risk profile of patients in each trial was different (for example the mean CHADS2 score of patients in the RE-LY study was 2.1, compared to 3.47 in the ROCKET-AF trial).

Other issues which should be considered are the twice-daily dosing of dabigatran and apixaban; the greater reliance on renal excretion of dabigatran; and drug interactions (as discussed above). Local policies should be followed where these exist.

Figure 9: Oral anticoagulation for stroke prevention
Figure 8. Oral anticoagulation for stroke prevention

Cardioversion of AF

ispIschaemic stroke rates following cardioversion are between 5 and 7% in non-anticoagulated patients, which can be reduced to 0.5 to 1.6% with warfarin.24 Current ESC guidelines advise anticoagulation with an INR of 2–3 for at least three weeks before and four weeks after cardioversion.16 Based on analysis of data on over 1,200 patients who underwent cardioversion during the RE-LY trial, dabigatran appears to be as safe and effective as warfarin, and is approved by ESC as an option.16

Since these guidelines were published, a similar analysis of data from the ARISTOTLE trial (apixaban) has been performed,27 and a randomised trial of rivaroxaban versus warfarin for cardioversion published (EX-VeRT28). Again this shows similar efficacy and safety to warfarin, including in the context of early cardioversion with the use of transoesophageal echocardiography to exclude thrombus.

Strict compliance with treatment is crucial if NOACs are to be used pre-cardioversion, as adequacy of anticoagulation cannot be confirmed by measurement of INR, as it can with warfarin. However, it is likely that local protocols will begin to adopt NOACs for this indication.

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22. Graham DJ, et al. Cardiovascular, Bleeding, and Mortality Risks in Elderly Medicare Patients Treated with Dabigatran or Warfarin for Non-Valvular Atrial Fibrillation. Circulation 2014.

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24. Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013;369:2093–104.

25. Gorog D. Rivaroxaban in non-valvular AF – UK experience in perspective. Br J Cardiol 2014;21(suppl 1):S1–S11.

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27. Flaker G, Lopes RD, Al-Khatib SM et al. Efficacy and safety of apixaban in patients after cardioversion for atrial fibrillation: insights from the ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation). J Am Coll Cardiol 2014;63: 1082–7.

28. Cappato R, Ezekowitz MD, Klein AL et al. Rivaroxaban vs. vitamin K antagonists for cardioversion in atrial fibrillation. Eur Heart J 2014;35:3346–55.

All available from (accessed 14/02/13)

Online resources

The Scottish Medicine Consortium:

The British National Formulary:

The National Institute for Health and Clinical Excellence (NICE):

Further reading

Hicks T, Stewart F, Eisinga A. NOACs versus warfarin for stroke prevention in patients with AF: a systematic review and meta-analysis. Open Heart 2016;3:e000279.

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