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The Risk of Myocardial Infarction in Patients with Atrial Fibrillation Taking a Direct Thrombin Inhibitor: Myths and Reality

https://doi.org/10.20996/1819-6446-2020-04-17

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Abstract

The purpose of this review is to analyze the results of randomized clinical trials, meta-analyses of cohort and observational studies in real clinical practice on the influence of dabigatran etexilate on the risk of myocardial infarction in patients with atrial fibrillation. A pivotal RE-LY study on dabigatran use in patients with atrial fibrillation did not show statistically significant differences in the frequency of myocardial infarction between any of the doses of dabigatran and warfarin, and the risk of coronary events did not depend on the presence of coronary heart disease or myocardial infarction in the patient's history. Subsequently, a number of meta-analyses have reported an increased risk of myocardial infarction when dabigatran was administered to patients with atrial fibrillation. In general, these studies were characterized by conflicting data, which did not allow to draw any definite conclusions regarding the use of dabigatran in relation to the risk of myocardial infarction. Two FDA cohort observational studies were published in 2014 and 2017, and the former was significantly criticized by experts, and the results of the second study did not provide a definitive answer to the question about the importance of the effect of dabigatran on the development of myocardial infarction in patients with atrial fibrillation. Even more "confusing" the problem arose after the publication of meta-analyses of randomized trials, which showed that the risk of myocardial infarction was increased in patients treated with direct oral anticoagulants compared to patients treated with warfarin. This review provides high quality evidence for the efficacy of dabigatran in preventing myocardial infarction and other vascular complications in patients with atrial fibrillation.

About the Authors

B. A. Tatarsky
Almazov National Medical Research Centre
Russian Federation

Tatarsky B. Alekseevich – MD, PhD, Professor, Head of Clinical Arrhythmology Research Laboratory

Akkuratova ul. 2, St. Petersburg, 197341



N. V. Kazennova
Almazov National Medical Research Centre
Russian Federation

Natalia V. Kazennova – MD, PhD, Researcher, Clinical Arrhythmology Research Laboratory

Akkuratova ul. 2, St. Petersburg, 197341



D. A. Napalkov
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Napalkov D. Alexandrovich – MD, PhD, Professor, Chair of Faculty Therapy №1

Trubetskaya ul. 8-2, Moscow, 119991



References

1. Connolly S., Ezekowitz M., Yusuf S., et al. Dabigatran versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med. 2009;361:1139-51. DOI:10.1056/NEJMoa0905561.

2. Patel M., Mahaffey K., Garg J., et al. Rivaroxaban versus Warfarin in Nonval-vular Atrial Fibrillation. N Engl J Med 2011;365:883-89. DOI:10.1056/NEJMoa1009638.

3. Granger C., Alexander J., McMurray J. et al. Apixaban versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2011;365:981-92. DOI:10.1056/NEJMoa1107039.

4. Giugliano R.P., Ruff C.T., Braunwald E., et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013;369:2093-104. DOI:10.1056/NEJMoa1310907

5. Kirchhof P., Benussi Si., Kotecha D., et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37(38):2893-962. DOI:10.1093/eurheartj/e.

6. Banerjee A., Lane D.A., Torp-Pedersen C., et al. Net clinical benefit of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus no treatment in a 'real world' atrial fibrillation population: a modelling analysis based on a nationwide cohort study. Thromb Haemost. 2012;107:584-89. DOI:10.1160/TH11-11-0784.

7. Pisters R., Nieuwlaat R., Lane D., et al. Potential net clinical benefit of population-wide implementation of apixaban and dabigatran among European patients with atrial fibrillation. A modelling analysis from the Euro Heart Survey. Thromb Haemost. 2013;109:328-36. DOI:10.1160/TH12-08-0539.

8. Soliman E.Z., Safford M.M., Muntner P., et al. Atrial fibrillation and the risk of myocardial infarction. JAMA Intern Med 2014;174:107-14. DOI:10.1001/jamainternmed.2013.11912.

9. Violi F., Soliman E.Z., Pignatelli P., Pastori D. Atrial fibrillation and myocardial infarction: a systematic review and appraisal of pathophysiologic mechanisms. J Am Heart Assoc. 2016;5:e003347. DOI:10.1161/JAHA.116.003347.

10. Kralev S., Schneider K., Lang S., et al. Incidence and severity of coronary artery disease in patients with atrial fibrillation undergoing first-time coronary angiography. PloS One. 2011;6:e24964. DOI:10.1371/journal.pone.0024964.

11. Lee C.J.Y., Pallisgaard J.L., Olesen J.B., et al. Antithrombotic therapy and first myocardial infarction in patients with atrial fibrillation. J Am Coll Cardiol. 2017;69:2901-9. DOI:10.1016/j.jacc.2017.04.033.

12. Hohnloser S.H., Oldgren J., Yang S., et al. Myocardial ischemic events in patients with atrial fibrillation treated with dabigatran or warfarin in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial. Circulation. 2012;125:669-76. DOI:10.1161/CIRCULATIONAHA.111.055970.

13. Uchino K., Hernandez A.V. Dabigatran Association With Higher Risk of Acute Coronary Events: Meta-analysis of Noninferiority Randomized Controlled Trials. Arch Intern Med. 2012;172:397-402. DOI:10.1001/archinternmed.2011.1666.

14. Mak K.H. Coronary and mortality risk of novel oral antithrombotic agents: a meta-analysis of large randomised trials. BMJ Open. 2012,2:e001592. DOI:10.1136/bmjopen-2012-001592.

15. Douxfils J., Buckinx F., Mullier F., et al. Dabigatran etexilate and risk of myocardial infarction, other cardiovascular events, major bleeding, and all-cause mortality: a systematic review and metaanalysis of randomized controlled trials. J Am Heart Assoc. 2014;3:e000515. DOI:10.1161/JAHA.113.000515.

16. Larsen T.B., Rasmussen L.H., Skjoth F., et al. Efficacy and safety of dabigatran etexilate and warfarin in ‘real world’ patients with atrial fibrillation. J Am Coll Cardiol. 2013;61(22):2264-73. DOI:10.1016/j.jacc.2013.03.020.

17. O’Riordan M. Two new analyses link dabigatran to MI risk. Medscape. [cited by Jul 10, 2019]. Available from: www.medscape.com/viewarticle/807621.

18. Sipahi I., Celik S., Akyol A. Letter to the editor for «Efficacy and safety of dabigatran etexilate and warfarin in «real world» patients with atrial fibrillation» by Larsen et al. Am Coll Cardiol. 2013;62(10):945-6. DOI:10.1016/j.jacc.2013.03.020.

19. Artang R., Rome E., Nielsen J.D., Vidaillet H.J. Meta-Analysis of Randomized Controlled Trials on Risk of Myocardial Infarction from the Use of Oral Direct Thrombin Inhibitors. Am J Cardiol. 2013;112(12):1973-9 . DOI:10.1016/j.amjcard.2013.08.027.

20. Dale B., Eikelboom J.W., Weitz J.I., et al. Dabigatran attenuates thrombin generation to a lesser extent than warfarin: could this explain their differential effects on intracranial hemorrhage and myocardial infarction? J Thromb Thrombolysis. 2013;35(2):295-301. DOI:10.1007/s11239-012-0857-9.

21. Lip G.Y.H., Lane D.A. Does warfarin for stroke thromboprophylaxis protect against MI in atrial fibrillation patients? Am J Med. 2010;123(9):785-9. DOI:10.1016/j.amjmed.2010.01.031.

22. Giglio A.F., Basile E., Santangeli P., et al. Increased risk of myocardial infarction with dabigatran: Fact or fiction? Journal of Cardiovascular Medicine. 2014;15:19-26. DOI:10.1016/j.pan.2015.03.007.

23. FDA Drug Safety Communication: FDA study of Medicare patients finds risks lower for stroke and death but higher for gastrointestinal bleeding with Pradaxa (dabigatran) compared to warfarin. [cited by Jul 10, 2019]. Available from: http://www.fda.gov/drugs/drugsafety/ucm396470.htm.

24. Nazarian R.M., Van Cott E.M., Zembowicz A., Duncan L.M. Warfarin-induced skin necrosis. Am Acad Dermatol. 2009;1:325-32. DOI:10.1016/j.jaad.2008.12.039.

25. Go A.S., Singer D.E., Toh S., et al. Outcomes of Dabigatran and Warfarin for Atrial Fibrillation in Contemporary Practice: A Retrospective Cohort Study. Ann Intern Med. 2017;167(12):845-854. DOI:10.7326/M16-1157

26. Stolk L.M., de Vries F., Ebbelaar C., et al. Risk of myocardial infarction in patients with atrial fibrillation using vitamin K antagonists, aspirin or direct acting oral anticoagulants. Br J Clin Pharmacol. 2017;83(8):1835-43. DOI:10.1111/bcp.13264.

27. Darwiche W., Bejan-Angoulvant T., Angoulvant D., et al. Risk of myocardial infarction and death in patients with atrial fibrillation treated with dabigatran or vitamin K antagonists Meta-analysis of observational analyses. Thromb Haemost. 2016;116:1150-8. DOI:10.1160/TH16-06-0483.

28. Wei A.H., Gu Z.C., Zhang C., et al. Increased risk of myocardial infarction with dabigatran etexilate: fact or fiction? A critical meta-analysis of over 580000 patients from integrating randomized controlled trials and real-world studies. Int J Cardiol. 2018;267:1-7. DOI:10.1016/j.ijcard.2018.05.048.

29. Lee C.J.Y., Gerds T.A., Carlson N., et al. Risk of myocardial infarction in anticoagulated patients with atrial fibrillation. J Am Coll Cardiol. 2018;72:17-26 . DOI:10.1016/j.jacc.2018.04.036.

30. Lauffenberger J.C., Farley J.F., Gehi A.K., et al. Effectiveness and safety of dabigatran and warfarin in real-world US patients with non-valvular atrial fibrillation: a retrospective cohort study. J Am Heart Assoc. 2015;4:e001798. DOI:10.1161/JAHA.115.001798.

31. Graham D.J., Reichman M.E., Wernecke M., et al. Cardiovascular, bleeding, and mortality risks in elderly Medicare patients treated with dabigatran or warfarin for nonvalvular atrial fibrillation. Circulation. 2015;131:157-64. DOI:10.1161/CIRCULATIONAHA.114.012061.

32. Devereaux P.J., Duceppe E., Guyatt G., et al. Dabigatran in patients with myocardial injury after non-cardiac surgery (MANAGE): an international, randomised, placebo-controlled trial. Lancet. 2018;39:2325-34. DOI:10.1016/S0140-6736(18)30832-8.


For citation:


Tatarsky B.A., Kazennova N.V., Napalkov D.A. The Risk of Myocardial Infarction in Patients with Atrial Fibrillation Taking a Direct Thrombin Inhibitor: Myths and Reality. Rational Pharmacotherapy in Cardiology. 2020;16(2):301-306. (In Russ.) https://doi.org/10.20996/1819-6446-2020-04-17

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