Evidence summary on oral anticoagulants and stroke prevention in atrial fibrillation
Successful use of all anticoagulants requires careful patient selection and routine clinical monitoring, to minimise the risk of thrombosis and bleeding.
- Most people with non-valvular atrial fibrillation (AF) need anticoagulants, including most of those at high risk of bleeding
- Address correctable risk factors for bleeding
- People well controlled on warfarin may not benefit clinically from switching to a newer oral anticoagulant (NOAC)
- Warfarin management
- Routine clinical monitoring is essential with all oral anticoagulants
- Careful selection of oral anticoagulants based on individual patient situations is crucial
Most people with non-valvular AF need anticoagulants, including most of those at high risk of bleeding
- Stroke risk in people with AF is under-treated even when CHADS2 scores indicate that anticoagulation is required.1
- Treat based on stroke risk; recommend oral anticoagulation for people at moderate to high risk of stroke (CHADS2 score ≥ 1) unless contraindicated.2
- Aspirin is not recommended for people with a CHADS2 score ≥ 1 unless anticoagulation is contraindicated.
- Assess stroke risk in people not currently taking oral anticoagulants (i.e. those at low risk of stroke) at least once a year.
- Use the HAS-BLED tool to identify correctable risk factors for bleeding and people who need increased clinical monitoring.
- People at high risk of bleeding are also at high risk of stroke and should not be precluded from anticoagulation but require regular clinical review.3
People well controlled on warfarin may not benefit clinically from switching to a newer oral anticoagulant
- In the key trials, dabigatran was only better than warfarin for reducing the incidence of stroke or systemic embolism when warfarin was not well controlled.4
- Apixaban was also better than warfarin for reducing the incidence of stroke,5 but the magnitude of these benefits seemed to be attenuated in patients and centres with better expected INR control.6,7
- Rivaroxaban was non-inferior to, but not better than, warfarin for reducing the incidence of stroke or systemic embolism (based on analysis of the intention-to-treat trial population),8 but non-inferiority was not demonstrated when warfarin was well controlled.9,10
- Of the three NOACs only apixaban reduced the incidence of major bleeding compared with warfarin when warfarin was well controlled.4,6–8
- Absolute risk reductions in incidence of intracranial haemorrhage with NOACs were small compared with those for warfarin,4,8,11 and dabigatran 150 mg and rivaroxaban were associated with an increased risk of major gastrointestinal bleeds.4,8
- Consider warfarin as first-line treatment for stroke prevention.2
- Dabigatran, rivaroxaban and apixaban are recommended as second-line treatments2 and are subsidised by the Pharmaceutical Benefits Scheme for the prevention of stroke or systemic embolism in people with non-valvular AF.9
- Anticoagulation with warfarin does not have to be achieved rapidly. A slow loading course is safe and achieves a stable INR of 2–3 in 3–4 weeks in most people.11
- Provide information to patients on the importance of dosing, monitoring and dietary, alcohol and drug interactions, as this is likely to increase safe use of warfarin.12 Discuss these key points of warfarin management with patients.
- There are currently no readily available and validated methods for monitoring or reversing the activity of the NOACs, so bleeding risk assessment is especially important in people taking these medicines.
- Ensure good patient adherence to dosing, as the newer agents have a much shorter half-life than warfarin and the risk of stroke is greater if a dose is missed.3
There is currently no evidence suggesting which patients would benefit the most from treatment with NOACs. Patients with poor adherence should not be switched from warfarin to a NOAC.
- are only suitable for stroke prevention in people with non-valvular AF
- are contraindicated in people with severe renal impairment (creatinine clearance < 30 mL/minute or, for apixaban, creatinine clearance < 25 mL/minute).
There have been no head-to-head studies to date comparing efficacy and safety of the NOACs.
- Ogilvie IM, Newton N, Welner SA, et al. Underuse of oral anticoagulants in atrial fibrillation: a systematic review. Am J Med 2010;123:638–45 e4. [PubMed]
- eTG complete [online]. Therapeutic Guidelines: Cardiovascular. Version 6. Melbourne: Therapeutic Guidelines Limited, 2012.
- Camm AJ, Lip GY, De Caterina R, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Europace: European pacing, arrhythmias, and cardiac electrophysiology: journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. Eur Heart J 2012;33:2719–47. [PubMed]
- Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. [Erratum appears in N Engl J Med 2010;363:1877]. N Engl J Med 2009;361:1139–51. [PubMed]
- Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365:981–92. [PubMed]
- Wallentin L, Lopes RD, Hanna M, et al. Efficacy and safety of apixaban compared with warfarin at different levels of predicted INR control for stroke prevention in atrial fibrillation. Circulation 2013;127:2166–76. [PubMed]
- Canadian Agency for Drugs and Technologies in Health. Safety, Effectiveness, and Cost-Effectiveness of New Oral Anticoagulants Compared with Warfarin in Preventing Stroke and Other Cardiovascular Events in Patients with Atrial Fibrillation. 2012. http://www.cadth.ca/media/pdf/NOAC_Therapeutic_Review_final_report.pdf (accessed 20 August 2013).
- Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883–91. [PubMed]
- Australian Government Department of Health and Ageing. March 2013 PBAC Public Summary Documents by Meeting. Rivaroxaban (SPAF), tablet, 15 mg and 20 mg, Xarelto. http://www.pbs.gov.au/info/industry/listing/elements/pbac-meetings/psd/2013-03/rivaroxaban-spaf (accessed 1 August 2012).
- Food and Drug Administration. FDA Draft Briefing Document for the Cardiovascular and Renal Drugs Advisory Committee (CRDAC), UCM270796. USA: FDA, 2011. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/drugs/CardiovascularandRenalDrugsAdvisoryCommittee/ucm270796.pdf (accessed 7 September 2012).
- National Institute for Health and Care Excellence 2014. Anticoagulation – oral – management. http://cks.nice.org.uk/anticoagulation-oral#azTab (accessed 8 May 2014).
- Guidelines & protocols advisary committee. Warfarin therapy management. British Columbia: British Columbia Medical Association, 2010.
- Bayer Australia Ltd. Xarelto (rivaroxaban) product information. 27 June 2013. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2009-PI-01020-3 (accessed 8 May 2014).
- Boehringer Ingelheim Pty Limited. Pradaxa (dabigatran) product information. 8 April 2014. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2009-PI-01177-3 (accessed 8 May 2014).
- Bristol-Myers Squibb Australia Pty Ltd. Product Information, Eliquis (apixaban). 4 July 2013. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2011-PI-03072-3 (accessed 8 May 2014).
- Connolly SJ, Eikelboom J, Joyner C, et al. Apixaban in patients with atrial fibrillation. N Engl J Med 2011;364:806–17. [PubMed]