This site is intended for healthcare professionals
Anticoagulation Therapy for Stroke Prevention
Declaration of sponsorship Pfizer and Bristol Myers Squibb

Disease awareness

Declaration of sponsorship Pfizer and Bristol Myers Squibb
Read time: 90 mins
Last updated:12th Mar 2020

Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, and strokes seem to be becoming more prevalent.1–3 Nevertheless, as many AF patients are asymptomatic, current epidemiological estimates might underestimate the number of people with the arrhythmia.4

AF patients can present with a wide range of sometimes debilitating symptoms, disease patterns and co-morbidities. But even when asymptomatic, AF can cause irreversible remodelling of the atria, which can perpetuate the arrhythmia and mean that over time, AF becomes progressively difficult to treat.5,6 As a result, early detection and rapid effective treatment are the cornerstones of care to alleviate symptoms and to reduce the risk of complications, including AF-related stroke.5 This section of the Learning Zone explores the background to AF-related strokes.

Epidemiology of Stroke

Stroke is common with, often, debilitating outcomes and the number of cases is set to rise markedly.


A common problem

Age-adjusted stroke incidence varies from 95–290 per 1,000,000 of the European population annually.3 About 1.1 million people experience a stroke in Europe each year. Transient ischaemic attacks (TIAs) are also common: the age-adjusted incidence ranged from 28–59 per 100,000 of the European population each year.3 


Register free for full access to

Epidemiology of atrial fibrillation 

AF is common in Europe, although the number of patients affected is probably underestimated.

AF incidence in Europe is between 21 and 41 per 100,000 of the population a year.2 AF prevalence in Europe varies from 1.9–2.9%.2,4,12 

However, insertable cardiac monitors can detect previously undocumented AF, suggesting that these figures are probably underestimates.13


Register free for full access to

Classification of atrial fibrillation 

Atrial fibrillation (AF) can present in several ways and correct classification can guide the choice of treatment. AF can present in several ways (Table 2) from a single isolated episode to a constant arrhythmia. 


Table 2. Classification of atrial fibrillation.5

Outcomes of stroke in Europe


Register free for full access to

Atrial fibrillation: an important stroke risk factor

The relationship runs both ways; atrial fibrillation (AF) causes strokes, while strokes can trigger AF.

The relationship between AF and stroke runs both ways. On the one hand, AF markedly increases the risk of stroke and systemic embolism.6 

For instance, AF increases stroke risk five-fold compared with people without the arrhythmia.2,6 The risk associated with AF is even higher in people with other stroke risk factors.20 Overall, AF may cause up to half of cardioembolic strokes and 10–30% of acute ischaemic strokes.4,11,19 


Register free for full access to

Pathophysiology of atrial fibrillation

A network of pathways influences the onset and persistence of atrial fibrillation (AF).

In any particular patient, the onset and persistence of AF may involve a complex network of mutually reinforcing pathogenic pathways that are influenced by age, genetic factors and acquired risk factors.6,25 

For example, acute coronary syndrome (ACS), such as myocardial infarction, as well as surgery or infection seem to precipitate a third of AF cases.19 


Register free for full access to

Pathophysiology of stroke in people with atrial fibrillation

Almost all AF patients show the pathophysiological changes that increase stroke risk.

AF’s characteristic aberrant electrical activity means that the atria do have time to contract and move the blood into the ventricles. So, blood remains in the atria and a clot may form. This, in turn, may embolise resulting in an ischaemic stroke.32 

Even short AF episodes can damage the atrial endothelium, which expresses factors that activate the coagulation cascade and as well as activating platelets and inflammatory cells. As a result, even short AF episodes can increase stroke risk.5


Register free for full access to

Symptoms of atrial fibrillation

Atrial fibrillation (AF) patients can present with a range of symptoms, but these are a poor guide to diagnosis.

AF patients may present with heart failure, myocardial infarction or another ACS, stroke or haemodynamic collapse and a variety of other, typically, non-specific symptoms (Figure 7).32

Common atrial fibrillation symptoms

Figure 7. Common atrial fibrillation symptoms.5

Register free for full access to

Diagnosis and diagnostic recommendations of atrial fibrillation

Atrial fibrillation diagnosis can be challenging, but ECG monitoring is the foundation of assessment.


An irregular pulse should raise a suspicion of AF: the sensitivity and specificity of pulse rate for AF is 94% and 72% respectively.19,32 Clinical presentation (Table 5) may indicate the type of AF, although about a third of AF episodes are asymptomatic.5,19


Register free for full access to

Burden of atrial fibrillation

AF impairs patients’ quality of life and accounts for up to 2% of healthcare budgets; stroke and hospitalisations drive the costs.

AF patients report impaired quality of life (QoL) that is independent of concomitant cardiovascular conditions.5 The impairment in QoL associated with AF can be similar to that in CHF and reflects the symptoms of the disease and complications, such as stroke.35 

AF’s impact on QoL may be especially marked in women, younger patients and those with comorbid conditions, such as coronary artery disease, COPD, obstructive sleep apnea or New York Heart Association (NYHA) classes II-IV CHF. Some of these factors could be modified and their presence may indicate that the patient requires a thorough QoL assessment.35


Register free for full access to

References for Anticoagulation Therapy for Stroke Prevention

1. Wyndham CR. Atrial fibrillation: The most common arrhythmia. Tex Hear Inst J. 2000;27(3):257–267.

2. Zoni-Berisso M, Lercari F, Carazza T, Domenicucci S. Epidemiology of atrial fibrillation: European perspective. Clin Epidemiol. 2014;6:213–220.

3. Béjot Y, Bailly H, Durier J, Giroud M. Epidemiology of stroke in Europe and trends for the 21st century. Press Méd. 2016;45(12, Part 2):e391–e398.

4. Contractor T, Khasnis A. Left atrial appendage closure in atrial fibrillation: A world without anticoagulation? Cardiol Res Pr. 2011;2011:752808.

5. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Hear J. 2016;37(38):2893–2962.

6. Rogers PA, Bernard ML, Madias C, Thihalolipavan S, Mark Estes NA, Morin DP. Current evidence-based understanding of the epidemiology, prevention, and treatment of atrial fibrillation. Curr Probl Cardiol. 2018;43(6):241–283.

7. Hankey GJ. Stroke. Lancet. 2017;389(10069):641–654.

8. Amarenco P, Bogousslavsky J, Caplan LR, Donnan GA, Hennerici MG. Classification of stroke subtypes. Cerebrovasc Dis. 2009;27(5):493–501.

9. Hopewell  C. J, Clarke R. Emerging risk factors for stroke. Stroke. 2016;47(6):1673–1678.

10. Heiss WD. The ischemic penumbra: Correlates in imaging and implications for treatment of ischemic stroke. Cerebrovasc Dis. 2011;32(4):307–320.

11. Bhatt H V, Fischer GW. Atrial fibrillation: Pathophysiology and therapeutic options. J Cardiothor Vasc An. 2015;29(5):1333–1340.

12. Pistoia F, Sacco S, Tiseo C, Degan D, Ornello R, Carolei A. The epidemiology of atrial fibrillation and stroke. Cardiol Clin. 2016;34(2):255–268.

13. Reiffel JA, Verma A, Kowey PR, Halperin JL, Gersh BJ, Wachter R, et al. Incidence of previously undiagnosed atrial fibrillation using insertable cardiac monitors in a high-risk population: The REVEAL AF Study. JAMA Cardiol. 2017;2(10):1120–1127.

14. Heeringa J, van der Kuip DAM, Hofman A, Kors JA, van Herpen G, Stricker BHC, et al. Prevalence, incidence and lifetime risk of atrial fibrillation: The Rotterdam study. Eur Hear J. 2006;27(8):949–953.

15. Pérez-Gómez F, Alegría E, Berjón J, Iriarte JA, Zumalde J, Salvador A, et al. Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation: a randomized multicenter study. J Am Coll Cardiol. 2004;44(8):1557–66.

16. Wang TY, Robinson LA, Ou F-S, Roe MT, Ohman EM, Gibler WB, et al. Discharge antithrombotic strategies among patients with acute coronary syndrome previously on warfarin anticoagulation: Physician practice in the CRUSADE registry. Am Heart J. 2008;155(2):361–368.

17. Kralev S, Schneider K, Lang S, Süselbeck T, Borggrefe M. Incidence and severity of coronary artery disease in patients with atrial fibrillation undergoing first-time coronary angiography. PLoS One. 2011;6(9):e24964.

18. Mehran R, Kalkman DN, Angiolillo DJ. Atrial fibrillation, with ACS and PCI: walking a tightrope. Eur Heart J. 2019;40(19):1563–1566.

19. Dilaveris PE, Kennedy HL. Silent atrial fibrillation: Epidemiology, diagnosis, and clinical impact. Clin Cardiol. 2017;40(6):413–418.

20. Lip GYH, Tse HF, Lane DA. Atrial fibrillation. Lancet. 2012;379(9816):648–661.

21. Kamel H, Okin PM, Elkind MS V, Iadecola C. Atrial fibrillation and mechanisms of stroke: Time for a new model. Stroke. 2016;47(3):895–900.

22. Friberg J, Scharling H, Gadsbøll N, Truelsen T, Jensen GB. Comparison of the impact of atrial fibrillation on the risk of stroke and cardiovascular death in women versus men (The Copenhagen City Heart Study). Am J Cardiol. 2004;94(7):889–894.

23. Hayden  T. D, Hannon N, Callaly E, Ní Chróinín D, Horgan G, Kyne L, et al. Rates and determinants of 5-year outcomes after atrial fibrillation–related stroke. Stroke. 2015;46(12):3488–3493.

24. Hahne K, Mönnig G, Samol A. Atrial fibrillation and silent stroke: Links, risks, and challenges. Vasc Heal Risk Manag. 2016;12:65–74.

25. Fatkin D, Santiago CF, Huttner IG, Lubitz SA, Ellinor PT. Genetics of atrial fibrillation: State of the art in 2017. Hear Lung Circ. 2017;26(9):894–901.

26. Gutierrez A, Chung MK. Genomics of atrial fibrillation. Curr Cardiol Rep. 2016;18(6):55.

27. Kim J-B. Channelopathies. Korean J Pediatr. 2014;57(1):1–18.

28. Herraiz-Martínez A, Llach A, Tarifa C, Gandía J, Jiménez-Sabado V, Lozano-Velasco E, et al. The 4q25 variant rs13143308T links risk of atrial fibrillation to defective calcium homoeostasis. Cardiovasc Res. 2018;115(3):578–589.

29. Veenhuyzen GD, Simpson CS, Abdollah H. Atrial fibrillation. CMAJ. 2004;171(7):755–760.

30. Roderick HL, Berridge MJ, Bootman MD. Calcium-induced calcium release. Curr Biol. 2003;13(11):R425.

31. Strollo PJ, Rogers RM. Obstructive sleep apnea. N Engl J Med. 1996;334(2):99–104.

32. Gutierrez C, Blanchard DG. Diagnosis and treatment of atrial fibrillation. Am Fam Physician. 2016;94(6):442–452.

33. Safavi-Naeini P, Rasekh A. Update on atrial fibrillation. Tex Hear I J. 2016;43(5):412–414.

34. Amerena J, Ridley D. An update on anticoagulation in atrial fibrillation. Hear Lung Circ. 2017;26(9):911–917.

35. Randolph TC, Simon DN, Thomas L, Allen LA, Fonarow GC, Gersh BJ, et al. Patient factors associated with quality of life in atrial fibrillation. Am Hear J. 2016;182:135–143.

36. Johnsen SP, Dalby LW, Täckström T, Olsen J, Fraschke A. Cost of illness of atrial fibrillation: A nationwide study of societal impact. BMC Heal Serv Res. 2017;17(1):714.

37. January T. C, Wann LS, Calkins H, Chen Lin Y, Cigarroa Joaquin E, Cleveland Joseph C, et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart R. Circulation. 2019;140(2):e125–e151.

38. Wollert KC, Kempf T, Wallentin L. Growth differentiation factor 15 as a biomarker in cardiovascular disease. 2017;63(1):140–151.

39. Mackman N, Tilley Rachel E, Key Nigel S. Role of the extrinsic pathway of blood coagulation in hemostasis and thrombosis. Arter Thromb Vasc Biol. 2007;27(8):1687–1693.

40. Saraf K, Morris P, Garg P, Sheridan P, Storey R. Non-vitamin K antagonist oral anticoagulants (NOACs): Clinical evidence and therapeutic considerations. Postgr Med J. 2014;90(1067):520–528.

41. Pirmohamed M. Warfarin: almost 60 years old and still causing problems. Br J Clin Pharmacol. 2006;62(5):509–511.

42. Hoffman M, Monroe DM. Impact of non-vitamin K antagonist oral anticoagulants from a basic science perspective. Arter Thromb Vasc Biol. 2017;37(10):1812–1818.

43. Almutairi AR, Zhou L, Gellad WF, Lee JK, Slack MK, Martin JR, et al. Effectiveness and safety of non–vitamin k antagonist oral anticoagulants for atrial fibrillation and venous thromboembolism: A systematic review and meta-analyses. Clin Ther. 2017;39(7):1456-1478.e36.

44. Kane S. NOAC, DOAC, or TSOAC: What should we call novel oral anticoagulants? Pharm Times. 2016;Available at

45. Lip GYH, Agnelli G. Edoxaban: A focused review of its clinical pharmacology. Eur Hear J. 2014;35(28):1844–1855.

46. Pan K-L, Singer DE, Ovbiagele B, Wu Y-L, Ahmed MA, Lee M. Effects of non-vitamin k antagonist oral anticoagulants versus warfarin in patients with atrial fibrillation and valvular heart disease: A systematic review and meta-analysis. J Am Hear Assoc. 2017;6(7):e005835.

47. Kovacs RJ, Flaker GC, Saxonhouse SJ, Doherty JU, Birtcher KK, Cuker A, et al. Practical management of anticoagulation in patients with atrial fibrillation. J Am Coll Cardiol. 2015;65(13):1340–1360.

48. Renda G, Ricci F, Giugliano RP, De Caterina R. Non–vitamin K antagonist oral anticoagulants in patients with atrial fibrillation and valvular heart disease. J Am Coll Cardiol. 2017;69(11):1363–1371.

49. Capodanno D, Alfonso F, Levine GN, Valgimigli M, Angiolillo DJ. ACC/AHA versus ESC guidelines on dual antiplatelet therapy. J Am Coll Cardiol. 2018;72(23):2915–2931.

50. Capodanno D, Angiolillo DJ. Management of antiplatelet and anticoagulant therapy in patients with atrial fibrillation in the setting of Acute Coronary Syndromes or Percutaneous Coronary Interventions. Circ Cardiovasc Interv. 2014;7(1):113–124.

51. Neumann F-J, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, et al. [2018 ESC/EACTS Guidelines on myocardial revascularization. The Task Force on myocardial revascularization of the European Society of Cardiology (ESC) and European Association for Cardio-Thoracic Surgery (EACTS)]. G Ital Cardiol (Rome).20(7):1–61.

52. Angiolillo DJ, Goodman SG, Bhatt DL, Eikelboom JW, Price MJ, Moliterno DJ, et al. Antithrombotic therapy in patients with atrial fibrillation treated with oral anticoagulation undergoing Percutaneous Coronary Intervention. Circulation. 2018;138(5):527–536.

53. Oldgren J, Steg PG, Hohnloser SH, Lip GYH, Kimura T, Nordaby M, et al. Dabigatran dual therapy with ticagrelor or clopidogrel after percutaneous coronary intervention in atrial fibrillation patients with or without acute coronary syndrome: a subgroup analysis from the RE-DUAL PCI trial. Eur Heart J. 2019;40(19):1553–1562.

54. Vranckx P, Lewalter T, Valgimigli M, Tijssen JG, Reimitz P-E, Eckardt L, et al. Evaluation of the safety and efficacy of an edoxaban-based antithrombotic regimen in patients with atrial fibrillation following successful percutaneous coronary intervention (PCI) with stent placement: Rationale and design of the ENTRUST-AF PCI trial. Am Heart J. 2018;196:105–112.

55. Lopes RD, Heizer G, Aronson R, Vora AN, Massaro T, Mehran R, et al. Antithrombotic therapy after Acute Coronary Syndrome or PCI in atrial fibrillation. N Engl J Med. 2019;380(16):1509–1524.

56. Lopes RD, Hong H, Harskamp RE, Bhatt DL, Mehran R, Cannon CP, et al. Safety and efficacy of antithrombotic strategies in patients with atrial fibrillation undergoing percutaneous coronary intervention. JAMA Cardiol. 2019. doi:10.1001/jamacardio.2019.1880.