Anticoagulation in atrial fibrillation

This is the poster-child for clinical epidemiologists wanting to illustrate how to calculate risk benefit ratios, mainly because of the rare ability to balance risk and harms in the same metric (embolic stroke causing hemiplegia and mortality versus major CNS bleed causing hemiplegia and mortality). In practice our performance sometimes falls short both in terms of doing the calculations (fairly easy now with the online calculators) but also in how we still tend to ramp up risk perceived riskin elderly patients and under-use anticoagulation. A pertinent factor which does weigh in here and is not mentioned in risk profiling is ease (or otherwise with which INR monitoring can be done in already disabled patients, and the family costs involved with monthly transport of such patients.

Risk of stroke in patients with atrial fibrillation

This varies with type, with non-paroxysmal AF having a higher risk¹ – the same review also found an increase in mortality (HR 1.2, 95% CI 1.085–1.365) in sustained AF. Definitions of what constitute ‘valvular’ atrial fibrillation differ² and it is unclear whether there is anything specific about the AF in these patients that changes risk, or whether (more likely) the increased risk is simply additive – patients with valvular abnormalities are also at risk of thromboembolic phenomena even if not in atrial fibrillation. The same review suggests that patients with rheumatic mitral valve, particularly mitral stenosis, or mechanical prostheses are actually the high risk group, and most other patients with AF associated with valvulopathies (aortic stenosis, aortic regurgitation, non-rheumatic mitral regurgitation, bioprosthesis, valve repair) are not at higher risk than patients with so-called non-valvular AF. An observational cohort on AF in mitral regurgitation found that this condition did not seem to increase stroke risk, perhaps related to the hypothesis that the regurgitation flushes clot out of the atrial and left atrial appendage using a ‘washing machine’ effect….³

Exact rates of thrombo-embolic risk without anticoagulation are based on older pre-anticoagulation observational work; for prosthetic valves not on warfarin, it is about 4% per year, dropping to 1% per year if on warfarin. Aortic valve prosthesis risk is lower than that for the mitral valve and is probably closer to 2% per year without anticoagulation⁴.

Deciding whether to anticoagulate

This is based on the well-know scoring systems which are now readily available:

The combined CHADVASC and HASBLED calculator available here is convenient in that information is only entered once, but use whichever one you find convenient and accessible.

Can you use aspirin to reduce thrombo-embolic rate in atrial fibrillation?

The short answer is no. An early single trial with three arms compared warfarin, aspirin and placebo and showed similar bleeding rates and that aspirin was about half as effective as warfarin but seemed to do something.⁵ The evidence that outcomes are worse (fewer strokes prevented and no less bleeding) with aspirin compared to warfarin is, however, now relatively clear ⁶. The bottom line is that aspirin as a sop to one’s conscience in an instance where warfarin seems too risky is no longer sensible – apart from lack of benefit, it may cause harm. ⁷

Target INR on warfarin

The target INR will vary depending on bleeding risk and stability of control, but time in the therapeutic range is as important, if not more so, than the exact level of INR targetted. In general, aim for a value in the range from 2 to 3.⁸

1. Anand N. Ganesan, Derek P. Chew, Trent Hartshorne, Joseph B. Selvanayagam, Philip E. Aylward, Prashanthan Sanders, Andrew D. McGavigan, The impact of atrial fibrillation type on the risk of thromboembolism, mortality, and bleeding: a systematic review and meta-analysis, European Heart Journal, Volume 37, Issue 20, 21 May 2016, Pages 1591–1602, https://doi.org/10.1093/eurheartj/ehw007 ↩

2. Raffaele De Caterina, A. John Camm, What is ‘valvular’ atrial fibrillation? A reappraisal, European Heart Journal, Volume 35, Issue 47, 14 December 2014, Pages 3328–3335, https://doi.org/10.1093/eurheartj/ehu352 ↩

3. Bisson A, Bernard A, Bodin A, Clementy N, Babuty D, Lip GYH, Fauchier L. Stroke and Thromboembolism in Patients With Atrial Fibrillation and Mitral Regurgitation. Circ Arrhythm Electrophysiol. 2019 Mar;12(3):e006990. doi: 10.1161/CIRCEP.118.006990. PMID: 30841722. ↩

4. Cannegieter SC, Rosendaal FR, Briet E. Thromboembolic and bleeding complications in patients with mechanical heart valve prostheses. Circulation 1994;89:635–641 ↩

5. Stroke Prevention in Atrial Fibrillation Study. Final results. Circulation. 1991 Aug;84(2):527-39. doi: 10.1161/01.cir.84.2.527. PMID: 1860198. ↩

6. Cameron C, Coyle D, Richter T, et al. Systematic review and network meta-analysis comparing antithrombotic agents for theprevention of stroke and major bleeding in patients with atrial fibrillation. BMJ Open 2014;4:e004301.doi:10.1136/bmjopen-2013-004301 ↩

7. Lin L, Lim WS, Zhou HJ, Khoo AL, Tan KT, Chew AP, Foo D, Chin JJ, Lim BP. Clinical and Safety Outcomes of Oral Antithrombotics for Stroke Prevention in Atrial Fibrillation: A Systematic Review and Network Meta-analysis. J Am Med Dir Assoc. 2015 Dec;16(12):1103.e1-19. doi: 10.1016/j.jamda.2015.09.008. Epub 2015 Oct 31. PMID: 26527225. ↩

8. Lip GYH, Banerjee A, Boriani G, Chiang CE, Fargo R, Freedman B, Lane DA, Ruff CT, Turakhia M, Werring D, Patel S, Moores L. Antithrombotic Therapy for Atrial Fibrillation: CHEST Guideline and Expert Panel Report. Chest. 2018 Nov;154(5):1121-1201. doi: 10.1016/j.chest.2018.07.040. Epub 2018 Aug 22. PMID: 30144419. ↩