M.S. Dzeshka, S.L. Boyko, N.V. Shpak, V.A. Snezhitskiy
Prevalence of atrial fibrillation (AF) is continuously increasing. Stroke in AF patients is the most unfavorable complication of arrhythmia, clinical course being severer, neurological deficit pronounced, and mortality higher compared to stroke patients without AF. Oral anticoagulation (OAC) results in significant reduction of stroke and systemic embolism but at the same time is compromised by haemorrhagic complications. High adherence to treatment is essential for effectiveness and safety of OAC. Nonetheless, poor adherence to treatment in case of chronic diseases requiring drug regimen remains unresolved. Social, economic and demographic factors, patient’s psychological markers, inertia of the healthcare system, formalism in the implementation of recommendations in routine clinical practice, violation of the continuity between inpatient and outpatient care, limited resources and other factors lead to low adherence among patients with AF. Refusal of OAC, intermittent treatment, delayed medication with OAC, failure to follow recommendations for the control of modifiable risk factors associated with anticoagulant therapy, are transformed into a high level of cardiovascular and cerebrovascular events in patients with AF. This article presents an analysis of three clinical cases of patients with complicated AF, discusses treatment from the standpoint of evidence-based medicine, the role of low adherence in the development of complications, and obstacles to increasing adherence.
keywords: atrial fibrillation, oral anticoagulation, adherence, stroke, myocardial infarction, intracranial bleeding

for references: M.S. Dzeshka, S.L. Boyko, N.V. Shpak, V.A. Snezhitskiy. Atrial fibrillation and adherence to oral anticoagulation: review of clinical cases. Neotlozhnaya kardiologiya i kardioovaskulyarnye riski [Emergency cardiology and cardiovascular risks], 2020, vol. 4, no. 2, pp. 1019–1028

1. Dzeshka M.S., Lip G.Y. Stroke And Bleeding Risk Assessment: Where Are We Now? J Atr Fibrillation, 2014, vol. 6, no. 6, pp. 49-57. doi: 10.4022/jafib.1042.
2. Kirchhof P., Benussi S., Kotecha D., Ahlsson A., Atar D., Casadei B., Castella M., Diener H.C., Heidbuchel H., Hendriks J., Hindricks G., Manolis A.S., Oldgren J., Popescu B.A., Schotten U., Van Putte B., Vardas P., ESC Scientific Document Group. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J, 2016, vol. 37, no. 38, pp. 2893-2962. doi: 10.1093/eurheartj/ehw210.
3. Dzeshka M.S., Lip G.Y. Antithrombotic and anticoagulant therapy for atrial fibrillation. Cardiol Clin, 2014, vol. 32, no. 4, pp. 585-599. doi: 10.1016/j.ccl.2014.07.009.
4. Raparelli V., Proietti M., Cangemi R., Lip G.Y., Lane D.A., Basili S. Adherence to oral anticoagulant therapy in patients with atrial fibrillation. Focus on non-vitamin K antagonist oral anticoagulants. Thromb Haemost, 2017, vol. 117, no. 2, pp. 209-218. doi: 10.1160/TH16-10-0757.
5. Dzeshka M.S., Shantsila A., Shantsila E., Lip G.Y.H. Atrial Fibrillation and Hypertension. Hypertension, 2017, vol. 70, no. 5, pp. 854-861. doi: 10.1161/HYPERTENSIONAHA.117.08934.
6. Dzeshka M.S., Shahid F., Shantsila A., Lip G.Y.H. Hypertension and Atrial Fibrillation: An Intimate Association of Epidemiology, Pathophysiology, and Outcomes. Am J Hypertens, 2017, vol. 30, no. 8, pp. 733-755. doi: 10.1093/ajh/hpx013.
7. Vermond R.A., Geelhoed B., Verweij N., Tieleman R.G., Van der Harst P., Hillege H.L., Van Gilst W.H., Van Gelder I.C., Rienstra M. Incidence of Atrial Fibrillation and Relationship With Cardiovascular Events, Heart Failure, and Mortality: A Community-Based Study From the Netherlands. J Am Coll Cardiol, 2015, vol. 66, no. 9, pp. 1000-1007. doi: 10.1016/j.jacc.2015.06.1314.
8. Mills K.T., Bundy J.D., Kelly T.N., Reed J.E., Kearney P.M., Reynolds K., Chen J., He J. Global Disparities of Hypertension Prevalence and Control: A Systematic Analysis of Population-Based Studies From 90 Countries. Circulation, 2016, vol. 134, no. 6, pp. 441-450. doi: 10.1161/CIRCULATIONAHA.115.018912.
9. Beyer-Westendorf J., Camm A.J., Coleman C.I., Tamayo S. Rivaroxaban real-world evidence: Validating safety and effectiveness in clinical practice. Thromb Haemost, 2016, vol. 116, no. Suppl. 2, pp. S13-S23. doi: 10.1160/TH16-06-0485.
10. McHorney C.A., Ashton V., Laliberte F., Germain G., Wynant W., Crivera C., Schein J.R., Lefebvre P., Peterson E.D. Adherence to Rivaroxaban Compared with Other Oral Anticoagulant Agents Among Patients with Nonvalvular Atrial Fibrillation. J Manag Care Spec Pharm, 2017, vol. 23, no. 9, pp. 980-988. doi: 10.18553/jmcp.2017.23.9.980.
11. Coleman C.I., Haas S., Turpie A.G., Kuhls S., Hess S., Evers T., Amarenco P., Kirchhof P., Camm A.J., Investigators X. Impact of Switching From a Vitamin K Antagonist to Rivaroxaban on Satisfaction With Anticoagulation Therapy: The XANTUS-ACTS Substudy. Clin Cardiol, 2016, vol. 39, no. 10, pp. 565-569. doi: 10.1002/clc.22565.
12. Dzeshka M.S., Lip G.Y. Warfarin versus dabigatran etexilate: an assessment of efficacy and safety in patients with atrial fibrillation. Expert Opin Drug Saf, 2015, vol. 14, no. 1, pp. 45-62. doi: 10.1517/14740338.2015.973847.
13. Dzeshka M.S., Lip G.Y. Non-vitamin K oral anticoagulants in atrial fibrillation: Where are we now? Trends Cardiovasc Med, 2015, vol. 25, no. 4, pp. 315-336. doi: 10.1016/j.tcm.2014.10.017.
14. Vene N., Mavri A., Gubensek M., Tratar G., Vizintin Cuderman T., Pohar Perme M., Blinc A. Risk of Thromboembolic Events in Patients with Non-Valvular Atrial Fibrillation After Dabigatran or Rivaroxaban Discontinuation - Data from the Ljubljana Registry. PLoS One, 2016, vol. 11, no. 6, pp. e0156943. doi: 10.1371/journal.pone.0156943.
15. Urbonas G., Valius L., Sakalyte G., Petniunas K., Petniuniene I. The Quality of Anticoagulation Therapy among Warfarin-Treated Patients with Atrial Fibrillation in a Primary Health Care Setting. Medicina (Kaunas), 2019, vol. 55, no. 1, pp. doi: 10.3390/medicina55010015.
16. Raparelli V., Proietti M., Butta C., Di Giosia P., Sirico D., Gobbi P., Corrao S., Davi G., Vestri A.R., Perticone F., Corazza G.R., Violi F., Basili S. Medication prescription and adherence disparities in non valvular atrial fibrillation patients: an Italian portrait from the ARAPACIS study. Intern Emerg Med, 2014, vol. 9, no. 8, pp. 861-870. doi: 10.1007/s11739-014-1096-1.
17. Banerjee A., Benedetto V., Gichuru P., Burnell J., Antoniou S., Schilling R.J., Strain W.D., Ryan R., Watkins C., Marshall T., Sut ton C.J. Adherence and persistence to direct oral anticoagulants in atrial fibrillation: a population-based study. Heart, 2020, vol. 106, no. 2, pp. 119-126. doi: 10.1136/heartjnl-2019-315307.
18. Rose A.J., Miller D.R., Ozonoff A., Berlowitz D.R., Ash A.S., Zhao S., Reisman J.I., Hylek E.M. Gaps in monitoring during oral anticoagulation: insights into care transitions, monitoring barriers, and medication nonadherence. Chest, 2013, vol. 143, no. 3, pp. 751-757. doi: 10.1378/chest.12-1119.
19. Hylek E.M., Go A.S., Chang Y., Jensvold N.G., Henault L.E., Selby J.V., Singer D.E. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N Engl J Med, 2003, vol. 349, no. 11, pp. 1019-1026. doi: 10.1056/NEJMoa022913.
20. Auer E., Frey S., Kaesmacher J., Hakim A., Seiffge D.J., Goeldlin M., Arnold M., Fischer U., Jung S., Meinel T.R. Stroke severity in patients with preceding direct oral anticoagulant therapy as compared to vitamin K antagonists. J Neurol, 2019, vol. 266, no. 9, pp. 2263-2272. doi: 10.1007/s00415-019-09412-y.
21. Wang C., Wang Y., Wang C., Zhao X., Liu L., Liu G., Wang D.Z., Li H., Wang Y. Anticoagulation-related reduction of first-ever stroke severity in Chinese patients with atrial fibrillation. J Clin Neurosci, 2014, vol. 21, no. 10, pp. 1755-1760. doi: 10.1016/j.jocn.2014.01.022.
22. Tziomalos K., Giampatzis V., Bouziana S.D., Spanou M., Kostaki S., Papadopoulou M., Dourliou V., Sofogianni A., Savopoulos C., Hatzitolios A.I. Adequacy of preadmission oral anticoagulation with vitamin K antagonists and ischemic stroke severity and outcome in patients with atrial fibrillation. J Thromb Thrombolysis, 2016, vol. 41, no. 2, pp. 336-342. doi: 10.1007/s11239-015-1262-y.
23. Powers W.J., Rabinstein A.A., Ackerson T., Adeoye O.M., Bambakidis N.C., Becker K., Biller J., Brown M., Demaerschalk B.M., Hoh B., Jauch E.C., Kidwell C.S., Leslie-Mazwi T.M., Ovbiagele B., Scott P.A., Sheth K.N., Southerland A.M., Summers D.V., Tirschwell D.L. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke, 2019, vol. 50, no. 12, pp. e344-e418. doi: 10.1161/STR.0000000000000211.
24. Dzeshka M.S., Pastori D., Lip G.Y.H. Direct oral anticoagulant reversal: how, when and issues faced. Expert Rev Hematol, 2017, vol. 10, no. 11, pp. 1005-1022. doi: 10.1080/17474086.2017.1379896.
25. Berrouschot J., Stoll A., Hogh T., Eschenfelder C.C. Intravenous Thrombolysis With Recombinant Tissue-Type Plasminogen Activator in a Stroke Patient Receiving Dabigatran Anticoagulant After Antagonization With Idarucizumab. Stroke, 2016, vol. 47, no. 7, pp. 1936-1938. doi: 10.1161/STROKEAHA.116.013550.
26. Lin Y.T., Lai Y.J., Lai T.H. Idarucizumab for Intravenous Thrombolysis and Endovascular Thrombectomy in Acute Stroke: A Case Report. J Emerg Med, 2020, vol. 58, no. 3, pp. e113-e116. doi: 10.1016/j.jemermed.2019.09.040.
27. Steffel J., Verhamme P., Potpara T.S., Albaladejo P., Antz M., Desteghe L., Georg Haeusler K., Oldgren J., Reinecke H., Roldan-Schilling V., Rowell N., Sinnaeve P., Collins R., Camm A.J., Heidbuchel H., ESC Scientific Document Group. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: executive summary. Europace, 2018, vol. 20, no. 8, pp. 1231-1242. doi: 10.1093/europace/euy054.
28. Seiffge D.J., Werring D.J., Paciaroni M., Dawson J., Warach S., Milling T.J., Engelter S.T., Fischer U., Norrving B. Timing of anticoagulation after recent ischaemic stroke in patients with atrial fibrillation. Lancet Neurol, 2019, vol. 18, no. 1, pp. 117-126. doi: 10.1016/S1474-4422(18)30356-9.
29. Dzeshka M.S., Lip G.Y. Specific risk scores for specific purposes: use CHA2DS2-VASc for assessing stroke risk, and use HAS-BLED for assessing bleeding risk in atrial fibrillation. Thromb Res, 2014, vol. 134, no. 2, pp. 217-218. doi: 10.1016/j.thromres.2014.06.003.
30. Olesen J.B., Lip G.Y., Lindhardsen J., Lane D.A., Ahlehoff O., Hansen M.L., Raunso J., Tolstrup J.S., Hansen P.R., Gislason G.H., Torp-Pedersen C. Risks of thromboembolism and bleeding with thromboprophylaxis in patients with atrial fibrillation: A net clinical benefit analysis using a ‘real world’ nationwide cohort study. Thromb Haemost, 2011, vol. 106, no. 4, pp. 739-749. doi: 10.1160/TH11-05-0364.
31. Lahaye S., Regpala S., Lacombe S., Sharma M., Gibbens S., Ball D., Francis K. Evaluation of patients’ attitudes towards stroke prevention and bleeding risk in atrial fibrillation. Thromb Haemost, 2014, vol. 111, no. 3, pp. 465-473. doi: 10.1160/TH13-05-0424.
32. Poli L., Grassi M., Zedde M., Marcheselli S., Silvestrelli G., Sessa M., Zini A., Paciaroni M., Azzini C., Gamba M., Toriello A., Tassi R., Giorli E., Calabro R.S., Ritelli M., De Vito A., Pugliese N., Martini G., Lanari A., Lodigiani C., Padroni M., De Giuli V., Caria F., Morotti A., Costa P., Strambo D., Corato M., Pascarella R., Del Sette M., Malferrari G., Colombi M., Padovani A., Pezzini A., Multicenter Study on Cerebral Hemorrhage in Italy I. Anticoagulants Resumption after Warfarin-Related Intracerebral Haemorrhage: The Multicenter Study on Cerebral Hemorrhage in Italy (MUCH-Italy). Thromb Haemost, 2018, vol. 118, no. 3, pp. 572-580. doi: 10.1055/s-0038-1627454.
33. Murthy S.B., Gupta A., Merkler A.E., Navi B.B., Mandava P., Iadecola C., Sheth K.N., Hanley D.F., Ziai W.C., Kamel H. Restarting Anticoagulant Therapy After Intracranial Hemorrhage: A Systematic Review and Meta-Analysis. Stroke, 2017, vol. 48, no. 6, pp. 1594-1600. doi: 10.1161/STROKEAHA.116.016327.
34. Korompoki E., Filippidis F.T., Nielsen P.B., Del Giudice A., Lip G.Y.H., Kuramatsu J.B., Huttner H.B., Fang J., Schulman S., Marti-Fabregas J., Gathier C.S., Viswanathan A., Biffi A., Poli D., Weimar C., Malzahn U., Heuschmann P., Veltkamp R. Long-term antithrombotic treatment in intracranial hemorrhage survivors with atrial fibrillation. Neurology, 2017, vol. 89, no. 7, pp. 687-696. doi: 10.1212/WNL.0000000000004235.
35. Paciaroni M., Agnelli G. Should oral anticoagulants be restarted after warfarin-associated cerebral haemorrhage in patients with atrial fibrillation? Thromb Haemost, 2014, vol. 111, no. 1, pp. 14-18. doi: 10.1160/TH13-08-0667.
36. Dzeshka M.S., Lip G.Y. Edoxaban for reducing the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation. Expert Opin Pharmacother, 2015, vol. 16, no. 17, pp. 2661-2678. doi: 10.1517/14656566.2015.1104301.
37. Inohara T., Xian Y., Liang L., Matsouaka R.A., Saver J.L., Smith E.E., Schwamm L.H., Reeves M.J., Hernandez A.F., Bhatt D.L., Peterson E.D., Fonarow G.C. Association of Intracerebral Hemorrhage Among Patients Taking Non-Vitamin K Antagonist vs Vitamin K Antagonist Oral Anticoagulants With In-Hospital Mortality. JAMA, 2018, vol. 319, no. 5, pp. 463-473. doi: 10.1001/jama.2017.21917.
38. Sembill J.A., Kuramatsu J.B., Schwab S., Huttner H.B. Resumption of oral anticoagulation after spontaneous intracerebral hemorrhage. Neurological Research and Practice, 2019, vol. 1, no. 1, pp. 12. doi: 10.1186/s42466-019-0018-0.
39. Dzeshka M.S., Lip G.Y.H. Editorial commentary: Reversal agents in the era of non-vitamin k antagonists oral anticoagulants: Necessity or psychological crutch? Trends Cardiovasc Med, 2020, vol. 30, no. 2, pp. 91-92. doi: 10.1016/j.tcm.2019.04.007.
40. Lip G.Y.H., Collet J.P., Haude M., Byrne R., Chung E.H., Fauchier L., Halvorsen S., Lau D., Lopez-Cabanillas N., Lettino M., Marin F., Obel I., Rubboli A., Storey R.F., Valgimigli M., Huber K., ESC Scientific Document Group. 2018 Joint European consensus document on the management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous cardiovascular interventions: a joint consensus document of the European Heart Rhythm Association (EHRA), European Society of Cardiology Working Group on Thrombosis, European Association of Percutaneous Cardiovascular Interventions (EAPCI), and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), Latin America Heart Rhythm Society (LAHRS), and Cardiac Arrhythmia Society of Southern Africa (CASSA). Europace, 2019, vol. 21, no. 2, pp. 192-193. doi: 10.1093/europace/euy174.
41. Dzeshka M.S., Brown R.A., Capodanno D., Lip G.Y. Antiplatelet and Antithrombotic Therapy in Patients with Atrial Fibrillation Undergoing Coronary Stenting. Interv Cardiol Clin, 2017, vol. 6, no. 1, pp. 91-117. doi: 10.1016/j.iccl.2016.08.007.
42. Dzeshka M.S., Brown R.A., Lip G.Y. Patients with atrial fibrillation undergoing percutaneous coronary intervention. Current concepts and concerns: part I. Pol Arch Med Wewn, 2015, vol. 125, no. 1-2, pp. 73-81. doi: 10.20452/pamw.2650.
43. Lopes R.D., Hong H., Harskamp R.E., Bhatt D.L., Mehran R., Cannon C.P., Granger C.B., Verheugt F.W.A., Li J., Ten Berg J.M., Sarafoff N., Vranckx P., Goette A., Gibson C.M., Alexander J.H. Optimal Antithrombotic Regimens for Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: An Updated Network Meta-analysis. JAMA Cardiol, 2020. doi: 10.1001/jamacardio.2019.6175.
44. Potpara T.S., Mujovic N., Proietti M., Dagres N., Hindricks G., Collet J.P., Valgimigli M., Heidbuchel H., Lip G.Y.H. Revisiting the effects of omitting aspirin in combined antithrombotic therapies for atrial fibrillation and acute coronary syndromes or percutaneous coronary interventions: meta-analysis of pooled data from the PIONEER AF-PCI, RE-DUAL PCI, and AUGUSTUS trials. Europace, 2020, vol. 22, no. 1, pp. 33-46. doi: 10.1093/europace/euz259.
45. Angiolillo D.J., Goodman S.G., Bhatt D.L., Eikelboom J.W., Price M.J., Moliterno D.J., Cannon C.P., Tanguay J.F., Granger C.B., Mauri L., Holmes D.R., Gibson C.M., Faxon D.P. Antithrombotic Therapy in Patients With Atrial Fibrillation Treated With Oral Anticoagulation Undergoing Percutaneous Coronary Intervention: A North American Perspective-2018 Update. Circulation, 2018, vol. 138, no. 5, pp. 527-536. doi: 10.1161/CIRCULATIONAHA.118.034722.
46. Hernandez I., He M., Chen N., Brooks M.M., Saba S., Gellad W.F. Trajectories of Oral Anticoagulation Adherence Among Medicare Beneficiaries Newly Diagnosed With Atrial Fibrillation. J Am Heart Assoc, 2019, vol. 8, no. 12, pp. e011427. doi: 10.1161/JAHA.118.011427.
47. Dzeshka M.S., Brown R.A., Lip G.Y. Patients with atrial fibrillation undergoing percutaneous coronary intervention: current concepts and concerns: part II. Pol Arch Med Wewn, 2015, vol. 125, no. 3, pp. 172-180. doi: 10.20452/pamw.2711.
48. Steinberg B.A., Hellkamp A.S., Lokhnygina Y., Patel M.R., Breithardt G., Hankey G.J., Becker R.C., Singer D.E., Halperin J.L., Hacke W., Nessel C.C., Berkowitz S.D., Mahaffey K.W., Fox K.A., Califf R.M., Piccini J.P., ROCKET-AF Steering Committee and Investigators. Higher risk of death and stroke in patients with persistent vs. paroxysmal atrial fibrillation: results from the ROCKET-AF Trial. Eur Heart J, 2015, vol. 36, no. 5, pp. 288-296. doi: 10.1093/eurheartj/ehu359.
49. Al-Khatib S.M., Thomas L., Wallentin L., Lopes R.D., Gersh B., Garcia D., Ezekowitz J., Alings M., Yang H., Alexander J.H., Flaker G., Hanna M., Granger C.B. Outcomes of apixaban vs. warfarin by type and duration of atrial fibrillation: results from the ARISTOTLE trial. Eur Heart J, 2013, vol. 34, no. 31, pp. 2464-2471. doi: 10.1093/eurheartj/eht135.
50. Olesen J.B., Torp-Pedersen C. Stroke risk in atrial fibrillation: Do we anticoagulate CHADS2 or CHA2DS2-VASc >/=1, or higher? Thromb Haemost, 2015, vol. 113, no. 6, pp. 1165-1169. doi: 10.1160/TH15-02-0154.
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