Anticoagulant therapy in secondary prevention of coronary events

Czech version

Authors: Jan Bultas
Authors‘ workplace: Ústav farmakologie 3. LF UK Praha, přednosta prof. MUDr. Jan Bultas, CSc.
Published in: Vnitř Lék 2014; 60(12): 1023-1032
Category: 70. birthday prof. MUDr. Michael Aschermann, DrSc., FESC, FACC

Overview

Secondary prevention of atherothrombotic events is the domain of antiplatelet therapy and according to present risk is used one drug strategy or combination of acetylsalicylic acid with ADP receptor blockers. The importance of the combination of dual antiplatelet therapy together with xabans or dabigatran was investigated in 6 clinical trials. Only one of them (ATLAS ACS 2-TIMI 51) indicated that treatment with small dose of rivaroxaban (2 × 2.5 mg) may be added to dual strategy of acetylsalicylic acid and clopidogrel. The risk of major bleeding event is increased and net clinical benefit is only about 0.5 % per year. Dual therapy with aspirin and prasugrel or tikagrelor is beneficial. In the second part of the review is discussed higher incidence of myocardial infarction in controlled group in the trial comparing treatment of dabigatran with warfarin. This relationship has not been resolved, however, in patients with higher risk of coronary events and indication of anticoagulant treatment with direct oral anticoagulants it is recommended to choose from xabans (apixaban and rivaroxaban).

Key words:
apixaban – dabigatran – myocardial infarction – rivaroxaban – secondary prevention – warfarin

Sources

1. 1Tsutsumi Y, Shimono J, Ohhigashi H et al. Analysis of the influence of dabigatran on coagulation factors and inhibitors. Int J Lab Hematol 2014; v tisku. Dostupné z DOI: <http://dx.doi.org/10.1111/ijlh.12270>.

2. Wienen W, Stassen JM, Priepke H et al. In-vitro profile and ex-vivo anticoagulant activity of the direct thrombin inhibitor dabigatran and its orally active prodrug, dabigatran etexilate. Thromb Haemost 2007; 98(1): 155–162.

3. Hoppensteadt D, Cunanan J, Lewis BE et al. Effect Of Dabigatran and Rivaroxiban On Thrombomodulin Mediated Activation Of Protein C and Thrombin Activated Fibrinolysis Inhibitor (TAFI). 56th ASH Annual Meeting 2014. Abstract 3641.

4. Wong PC, Crain EJ, Xin B et al. Apixaban, an oral, direct and highly selective factor Xa inhibitor: in vitro, antithrombotic and antihemostatic studies. J Thromb Haemost 2008; 6(5): 820–829.

5. Reilly PA, Lehr T, Haertter S et al. The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). J Am Coll Cardiol 2014; 63(4): 321–328.

6. Rothberg MB, Celestin C, Fiore LD et al. Warfarin plus aspirin after myocardial infarction or the acute coronary syndrome: meta-analysis with estimates of risk and benefit. Ann Intern Med 2005; 143(4): 241–250.

7. Mega JL, Braunwald E, Murphy SA et al. Rivaroxaban in patients stabilized after a ST-segment elevation myocardial infarction: results from the ATLAS ACS-2-TIMI-51 trial (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome-Thrombolysis In Myocardial Infarction-51. J Am Coll Cardiol 2013; 61(18): 1853–1859.

8. Krantz MJ, Kaul S. The ATLAS ACS 2-TIMI 51 trial and the burden of missing data: Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects With Acute Coronary Syndrome ACS 2-Thrombolysis In Myocardial Infarction 51. J Am Coll Cardiol 2013; 62(9): 777–781.

9. Komócsi A, Vorobcsuk A, Kehl D et al. Use of new-generation oral anticoagulant agents in patients receiving antiplatelet therapy after an acute coronary syndrome: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med 2012; 172(20): 1537–1545.

10. Hohnloser SH, 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(5): 669–676.

11. Artang R, Rome E, Nielsen JD et al. 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): 1973–1979.

12. 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 meta-analysis of randomized controlled trials. J Am Heart Assoc 2014; 3(3): e000515. Dostupné z DOI: <http:// doi: 10.1161/JAHA.113.000515>.

13. Larsen TB, Rasmussen LH, Skjøth F et al. Efficacy and safety of dabigatran etexilate and warfarin in “real-world” patients with atrial fibrillation: a prospective nationwide cohort study. J Am Coll Cardiol 2013; 61(22): 2264–2273.

14. Food and Drug Administration. FDA study of Medicare patients finds risks lower for stroke and death but higher for gastrointestinal bleeding with Pradaxa (dabigatran) compared to warfarin [press release]. 2014; May 13. Dostupné z WWW: <http://www.fda.gov/Drugs/DrugSafety/DrugSafetyPodcasts/ucm397327.htm>.

15. Sipahi I, Celik S, Tozun N. A comparison of results of the US food and drug administration‘s mini-sentinel program with randomized clinical trials: the case of gastrointestinal tract bleeding with dabigatran. JAMA Intern Med 2014; 174(1): 150–151.

16. 16.Wood S. FDA Review Finds No Increased Risk of MI With Dabigatran (Pradaxa). 2014;May 13. Dostupné z WWW: <<http://www.medscape.com/viewarticle/825080>>.

17. Collaborative overview of randomised trials of antiplatelet therapy-I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists‘ Collaboration. BMJ 1994; 308(6921): 81–106. Erratum in BMJ 1994; 308(6943): 1540.

18. Antithrombotic Trialists‘ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002; 324(7329): 71–86. Erratum in BMJ 2002; 324(7330): 141.

19. Wiviott SD, Braunwald E, McCabe CH et al. TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 15;357(20): 2001–2015.

20. Wallentin L, Becker RC, Budaj A et al. PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361(11): 1045–1057.