DOI QR코드

DOI QR Code

Antiplatelet Therapy Combinations and Thrombogenicity in Patients with Non-Valvular Atrial Fibrillation

  • Park, Yongwhi (Department of Internal Medicine, Gyeongsang National University School of Medicine, Cardiovascular Center, Gyeongsang National University Changwon Hospital) ;
  • Kim, Kye Hwan (Department of Internal Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital) ;
  • Kang, Min Gyu (Department of Internal Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital) ;
  • Ahn, Jong-Hwa (Department of Internal Medicine, Gyeongsang National University School of Medicine, Cardiovascular Center, Gyeongsang National University Changwon Hospital) ;
  • Jang, Jeong Yoon (Department of Internal Medicine, Gyeongsang National University School of Medicine, Cardiovascular Center, Gyeongsang National University Changwon Hospital) ;
  • Park, Hyun Woong (Department of Internal Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital) ;
  • Koh, Jin-Sin (Department of Internal Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital) ;
  • Park, Jeong-Rang (Department of Internal Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital) ;
  • Hwang, Seok-Jae (Department of Internal Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital) ;
  • Jeong, Young-Hoon (Department of Internal Medicine, Gyeongsang National University School of Medicine, Cardiovascular Center, Gyeongsang National University Changwon Hospital) ;
  • Hwang, Jin-Yong (Department of Internal Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital) ;
  • Lee, Hye Ryun (Department of Laboratory Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine) ;
  • Kwak, Choong Hwan (Department of Internal Medicine, Gyeongsang National University School of Medicine, Cardiovascular Center, Gyeongsang National University Changwon Hospital)
  • 투고 : 2016.10.31
  • 심사 : 2016.12.29
  • 발행 : 2017.05.31

초록

Background and objectives: Combination antiplatelet therapy reduces the risk of ischemic stroke compared with aspirin monotherapy in non-valvular atrial fibrillation (NVAF) patients. The underlying mechanism, however, remains unclear. In addition, the association between platelet inhibition and thrombogenicity in NVAF has not been evaluated. Subjects and methods: We randomized 60 patients with NVAF that were taking 100 mg of aspirin daily (>1 month) to adding 75 mg of clopidogrel daily (CLPD group), 100 mg of cilostazol twice daily (CILO group), or 1000 mg of omega-3 polyunsaturated fatty acid twice daily (PUFA group). Biomarkers (von Willebrand factor antigen [vWF:Ag], fibrinogen, D-dimer, and high-sensitivity C-reactive protein [hs-CRP]) and platelet reactivity (PR), which were the levels stimulated by adenosine diphosphate (ADP), thrombin-receptor agonist peptide, collagen, and arachidonic acid, were measured at baseline and 30-day follow-up. Results: Combination antiplatelet therapy significantly reduced vWF:Ag and fibrinogen levels (7.7 IU/dL, p=0.015 and 15.7 mg/dL, p=0.005, respectively), but no changes were found in D-dimer and hs-CRP levels. The CLPD and CILO groups showed fibrinogen and vWF:Ag level reductions (24.9 mg/dL, p=0.015 and 9.3 IU/dL, p=0.044, respectively), whereas the PUFA group did not show any differences in biomarkers. Irrespective of regimen, the changes in fibrinogen and vWF:Ag levels were mainly associated with the change in ADP-mediated PR (r=0.339, p=0.008 and r=0.322, p=0.012, respectively). Conclusion: In patients with NVAF, combination antiplatelet therapy showed reductions for vWF:Ag and fibrinogen levels, which may be associated with the inhibitory levels of ADP-mediated PR. The clinical implications of these findings need to be evaluated in future trials.

키워드

과제정보

연구 과제 주관 기관 : Gyeongsang National University

참고문헌

  1. Watson T, Shantsila E, Lip GY. Mechanisms of thrombogenesis in atrial fibrillation: Virchow's triad revisited. Lancet 2009;373:155-66. https://doi.org/10.1016/S0140-6736(09)60040-4
  2. Furie B, Furie BC. Mechanisms of thrombus formation. N Engl J Med 2008;359:938-49. https://doi.org/10.1056/NEJMra0801082
  3. McFadyen JD, Jackson SP. Differentiating haemostasis from thrombosis for therapeutic benefit. Thromb Haemost 2013;110:859-67. https://doi.org/10.1160/TH13-05-0379
  4. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016;37:2893-962. https://doi.org/10.1093/eurheartj/ehw210
  5. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association task force on practice guidelines and the Heart Rhythm Society. Circulation 2014;130:2071-104. https://doi.org/10.1161/CIR.0000000000000040
  6. Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 2014;383:955-62. https://doi.org/10.1016/S0140-6736(13)62343-0
  7. Bassand JP, Accetta G, Camm AJ, et al. Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF. Eur Heart J 2016;37:2882-9. https://doi.org/10.1093/eurheartj/ehw233
  8. Son MK, Lim NK, Cho MC, Park HY. Incidence and risk factors for atrial fibrillation in Korea: the national health insurance service database (2002-2010). Korean Circ J 2016;46:515-21. https://doi.org/10.4070/kcj.2016.46.4.515
  9. Sabir I, Khavandi K, Brownrigg J, Camm AJ. Oral anticoagulants for Asian patients with atrial fibrillation. Nat Rev Cardiol 2014;11:290-303. https://doi.org/10.1038/nrcardio.2014.22
  10. Suzuki S, Yamashita T, Kato T, et al. Incidence of major bleeding complication of warfarin therapy in Japanese patients with atrial fibrillation. Circ J 2007;71:761-5. https://doi.org/10.1253/circj.71.761
  11. Oh S, Goto S, Accetta G, et al. Vitamin K antagonist control in patients with atrial fibrillation in Asia compared with other regions of the world: real-world data from the GARFIELD-AF registry. Int J Cardiol 2016;223:543-7. https://doi.org/10.1016/j.ijcard.2016.08.236
  12. Choi JH, Cha JK, Huh JT. Adenosine diphosphate-induced platelet aggregation might contribute to poor outcomes in atrial fibrillationrelated ischemic stroke. J Stroke Cerebrovasc Dis 2014;23:e215-20. https://doi.org/10.1016/j.jstrokecerebrovasdis.2013.10.011
  13. Jaremo P, Eriksson M, Lindahl TL, Nilsson S, Milovanovic M. Platelets and acute cerebral infarction. Platelets 2013;24:407-11. https://doi.org/10.3109/09537104.2012.712168
  14. ACTIVE Investigators, Connolly SJ, Pogue J, et al. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med 2009;360:2066-78. https://doi.org/10.1056/NEJMoa0901301
  15. Kim D, Lee SH, Kim BJ, et al. Secondary prevention by stroke subtype: a nationwide follow-up study in 46108 patients after acute ischaemic stroke. Eur Heart J 2013;34:2760-7. https://doi.org/10.1093/eurheartj/eht185
  16. Shinohara Y, Katayama Y, Uchiyama S, et al. Cilostazol for prevention of secondary stroke (CSPS 2): an aspirin-controlled, double-blind, randomised non-inferiority trial. Lancet Neurol 2010;9:959-68. https://doi.org/10.1016/S1474-4422(10)70198-8
  17. Chowdhury R, Stevens S, Gorman D, et al. Association between fish consumption, long chain omega 3 fatty acids, and risk of cerebrovascular disease: systematic review and meta-analysis. BMJ 2012;345:e6698. https://doi.org/10.1136/bmj.e6698
  18. Larson MK, Ashmore JH, Harris KA, et al. Effects of omega-3 acid ethyl esters and aspirin, alone and in combination, on platelet function in healthy subjects. Thromb Haemost 2008;100:634-41. https://doi.org/10.1160/TH08-02-0084
  19. Lee JH, Cha JK, Lee SJ, Ha SW, Kwon SU. Addition of cilostazol reduces biological aspirin resistance in aspirin users with ischaemic stroke: a double-blind randomized clinical trial. Eur J Neurol 2010;17:434-42. https://doi.org/10.1111/j.1468-1331.2009.02837.x
  20. Moshfegh K, Redondo M, Julmy F, et al. Antiplatelet effects of clopidogrel compared with aspirin after myocardial infarction: enhanced inhibitory effects of combination therapy. J Am Coll Cardiol 2000;36:699-705. https://doi.org/10.1016/S0735-1097(00)00817-2
  21. Kim IS, Jeong YH, Kang MK et al. Correlation of high post-treatment platelet reactivity assessed by light transmittance aggregometry and the VerifyNow P2Y12 assay. J Thromb Thrombolysis 2010;30:486-95. https://doi.org/10.1007/s11239-010-0484-2
  22. ACTIVE Writing Group of the ACTIVE Investigators, Connolly S, Pogue J, et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet 2006;367:1903-12. https://doi.org/10.1016/S0140-6736(06)68845-4
  23. Siegbahn A, Oldgren J, Andersson U, et al. D-dimer and factor VIIa in atrial fibrillation - prognostic values for cardiovascular events and effects of anticoagulation therapy. A RE-LY substudy. Thromb Haemost 2016;115:921-30. https://doi.org/10.1055/s-0037-1615530
  24. Wu N, Chen X, Cai T, et al. Association of inflammatory and hemostatic markers with stroke and thromboembolic events in atrial fibrillation: a systematic review and meta-analysis. Can J Cardiol 2015;31:278-86. https://doi.org/10.1016/j.cjca.2014.12.002
  25. Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest 2010;137:263-72. https://doi.org/10.1378/chest.09-1584
  26. Dewilde WJ, Oirbans T, Verheugt FW, et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet 2013;381:1107-15. https://doi.org/10.1016/S0140-6736(12)62177-1
  27. Park Y, Franchi F, Rollini F, Angiolillo DJ. Update on oral antithrombotic therapy for secondary prevention following non-ST segment elevation myocardial infarction. Trends Cardiovasc Med 2016;26:321-34. https://doi.org/10.1016/j.tcm.2015.08.002
  28. Hori M, Connolly SJ, Zhu J, et al. Dabigatran versus warfarin: effects on ischemic and hemorrhagic strokes and bleeding in Asians and non-Asians with atrial fibrillation. Stroke 2013;44:1891-6. https://doi.org/10.1161/STROKEAHA.113.000990
  29. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883-91. https://doi.org/10.1056/NEJMoa1009638
  30. Hori M, Matsumoto M, Tanahashi N, et al. Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation - the J-ROCKET AF study -. Circ J 2012;76:2104-11. https://doi.org/10.1253/circj.CJ-12-0454

피인용 문헌

  1. Prognostic value of plasma von Willebrand factor levels in major adverse cardiovascular events: a systematic review and meta-analysis vol.20, pp.None, 2017, https://doi.org/10.1186/s12872-020-01375-7
  2. Effects of Monotherapy with Clopidogrel vs. Aspirin on Vascular Function and Hemostatic Measurements in Patients with Coronary Artery Disease: The Prospective, Crossover I-LOVE-MONO Trial vol.10, pp.12, 2017, https://doi.org/10.3390/jcm10122720