Skip to main content
SpringerLink
Log in

Effectiveness of Adding Antiplatelets to Oral Anticoagulants in Patients with Acute Ischemic Stroke with Atrial Fibrillation and Concomitant Large Artery Steno-Occlusion

  • Original Article
  • Published:
Translational Stroke Research Aims and scope Submit manuscript

Abstract

We investigated the effectiveness of adding antiplatelet (AP) to oral anticoagulant (OAC) treatment versus OAC treatment alone in patients with AIS with atrial fibrillation (AF) and significant large artery steno-occlusion (LASO). This study is a retrospective analysis of a nationwide, prospective, multicenter stroke registry between April 2008 and November 2017. Patients with acute (within 48 h of onset) and mild-to-moderate (NIHSS score ≤ 15) stroke with AF and concomitant LASO were identified. Antithrombotic regimens at discharge were categorized into OAC alone or OAC + AP. The primary outcome event was a composite of recurrent stroke, myocardial infarction, and all-cause mortality within 3 months of stroke. Among the 2553 patients (age, 73 ± 10 years; men, 50.4%), 78.8% were treated with OAC alone, and 21.2% were treated with OAC + AP. The primary outcome events were significantly more common in the OAC + AP group (6.7%) than the OAC alone group (4.3%) (p = 0.02). Weighted Cox proportional hazard analysis showed that OAC + AP increased the risk of 3-month primary outcome events compared with OAC alone (HR, 1.62 [1.06 to 2.46]). A potential interaction between the type of LASO and discharge antithrombotics was suggested (Pinteraction = 0.04); unlike in patients with complete occlusion (OAC + AP; HR, 2.00 [1.27–3.15]), OAC + AP was comparable with OAC alone for 3-month primary outcome in patients with moderate-to-severe stenosis (HR, 0.54 [0.17–1.70]). In conclusion, OAC + AP might increase the risk of 3-month outcome events compared with OAC alone in patients with AIS with AF and concomitant LASO. However, the effect of additional AP to OAC might differ according to LASO type.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Availability of Data and Material

Data used in this study are available upon reasonable request following submission of a legitimate academic research proposal to be assessed by the CRCS-K steering committee.

References

  1. Cardiogenic brain embolism. The second report of the cerebral embolism task force. Arch Neurol. 1989;46(7):727–43.

  2. Kim JY, Kang K, Kang J, Koo J, Kim DH, Kim BJ, et al. Executive summary of stroke statistics in Korea 2018: a report from the Epidemiology Research Council of the Korean Stroke Society. J Stroke. 2019;21(1):42–59. https://doi.org/10.5853/jos.2018.03125.

    Article  PubMed  Google Scholar 

  3. Schnabel RB, Yin X, Gona P, Larson MG, Beiser AS, McManus DD, et al. 50 year trends in atrial fibrillation prevalence, incidence, risk factors, and mortality in the Framingham heart study: a cohort study. Lancet. 2015;386(9989):154–62. https://doi.org/10.1016/S0140-6736(14)61774-8.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Wang JC, Bennett M. Aging and atherosclerosis: mechanisms, functional consequences, and potential therapeutics for cellular senescence. Circ Res. 2012;111(2):245–59. https://doi.org/10.1161/CIRCRESAHA.111.261388.

    Article  CAS  PubMed  Google Scholar 

  5. Kim YD, Cha MJ, Kim J, Lee DH, Lee HS, Nam CM, et al. Increases in cerebral atherosclerosis according to CHADS2 scores in patients with stroke with nonvalvular atrial fibrillation. Stroke. 2011;42(4):930–4. https://doi.org/10.1161/STROKEAHA.110.602987.

    Article  PubMed  Google Scholar 

  6. Kamel H, Okin PM, Elkind MS, Iadecola C. Atrial fibrillation and mechanisms of stroke: time for a new model. Stroke. 2016;47(3):895–900. https://doi.org/10.1161/STROKEAHA.115.012004.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Lehtola H, Airaksinen KEJ, Hartikainen P, Hartikainen JEK, Palomaki A, Nuotio I, et al. Stroke recurrence in patients with atrial fibrillation: concomitant carotid artery stenosis doubles the risk. Eur J Neurol. 2017;24(5):719–25. https://doi.org/10.1111/ene.13280.

    Article  CAS  PubMed  Google Scholar 

  8. Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke. EAFT (European Atrial Fibrillation Trial) Study Group. Lancet. 1993;342(8882):1255–62.

  9. Saxena R, Koudstaal P. Anticoagulants versus antiplatelet therapy for preventing stroke in patients with nonrheumatic atrial fibrillation and a history of stroke or transient ischemic attack. Cochrane Database Syst Rev. 2004;4:CD000187. https://doi.org/10.1002/14651858.CD000187.pub2.

    Article  Google Scholar 

  10. Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, Ezekowitz MD, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45(7):2160–236. https://doi.org/10.1161/STR.0000000000000024.

    Article  PubMed  Google Scholar 

  11. 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 Heart J. 2016;37(38):2893–962. https://doi.org/10.1093/eurheartj/ehw210.

    Article  PubMed  Google Scholar 

  12. Eikelboom JW, Connolly SJ, Bosch J, Dagenais GR, Hart RG, Shestakovska O, et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med. 2017;377(14):1319–30. https://doi.org/10.1056/NEJMoa1709118.

    Article  CAS  Google Scholar 

  13. Kim BJ, Park JM, Kang K, Lee SJ, Ko Y, Kim JG, et al. Case characteristics, hyperacute treatment, and outcome information from the clinical research center for stroke-fifth division registry in South Korea. J Stroke. 2015;17(1):38–53. https://doi.org/10.5853/jos.2015.17.1.38.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Kim BJ, Han MK, Park TH, Park SS, Lee KB, Lee BC, et al. Current status of acute stroke management in Korea: a report on a multicenter, comprehensive acute stroke registry. Int J Stroke. 2014;9(4):514–8. https://doi.org/10.1111/ijs.12199.

  15. Rassen JA, Glynn RJ, Rothman KJ, Setoguchi S, Schneeweiss S. Applying propensity scores estimated in a full cohort to adjust for confounding in subgroup analyses. Pharmacoepidemiol Drug Saf. 2012;21(7):697–709. https://doi.org/10.1002/pds.2256.

    Article  PubMed  Google Scholar 

  16. Wein T, Lindsay MP, Cote R, Foley N, Berlingieri J, Bhogal S, et al. Canadian stroke best practice recommendations: secondary prevention of stroke, sixth edition practice guidelines, update 2017. Int J Stroke. 2018;13(4):420–43. https://doi.org/10.1177/1747493017743062.

    Article  PubMed  Google Scholar 

  17. Shah R, Hellkamp A, Lokhnygina Y, Becker RC, Berkowitz SD, Breithardt G, et al. Use of concomitant aspirin in patients with atrial fibrillation: findings from the ROCKET AF trial. Am Heart J. 2016;179:77–86. https://doi.org/10.1016/j.ahj.2016.05.019.

    Article  CAS  PubMed  Google Scholar 

  18. So CH, Eckman MH. Combined aspirin and anticoagulant therapy in patients with atrial fibrillation. J Thromb Thrombolysis. 2017;43(1):7–17. https://doi.org/10.1007/s11239-016-1425-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hansen ML, Sorensen R, Clausen MT, Fog-Petersen ML, Raunso J, Gadsboll N, et al. Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Intern Med. 2010;170(16):1433–41. https://doi.org/10.1001/archinternmed.2010.271.

    Article  CAS  PubMed  Google Scholar 

  20. Kanter MC, Tegeler CH, Pearce LA, Weinberger J, Feinberg WM, Anderson DC, et al. Carotid stenosis in patients with atrial fibrillation. Prevalence, risk factors, and relationship to stroke in the stroke prevention in atrial fibrillation study. Arch Intern Med. 1994;154(12):1372–7.

    Article  CAS  Google Scholar 

  21. Gibson CM, Mehran R, Bode C, Halperin J, Verheugt FW, Wildgoose P, et al. Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med. 2016;375(25):2423–34. https://doi.org/10.1056/NEJMoa1611594.

    Article  CAS  Google Scholar 

  22. Cannon CP, Bhatt DL, Oldgren J, Lip GYH, Ellis SG, Kimura T, et al. Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation. N Engl J Med. 2017;377(16):1513–24. https://doi.org/10.1056/NEJMoa1708454.

    Article  CAS  PubMed  Google Scholar 

  23. 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):1509–24. https://doi.org/10.1056/NEJMoa1817083.

    Article  CAS  PubMed  Google Scholar 

  24. Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, 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(9921):955–62. https://doi.org/10.1016/S0140-6736(13)62343-0.

    Article  CAS  Google Scholar 

  25. Lee SR, Choi EK, Kwon S, Han KD, Jung JH, Cha MJ, et al. Effectiveness and safety of contemporary oral anticoagulants among Asians with nonvalvular atrial fibrillation. Stroke. 2019;50(8):2245–9. https://doi.org/10.1161/STROKEAHA.119.025536.

    Article  CAS  PubMed  Google Scholar 

  26. van Walraven C, Jennings A, Oake N, Fergusson D, Forster AJ. Effect of study setting on anticoagulation control: a systematic review and metaregression. Chest. 2006;129(5):1155–66. https://doi.org/10.1378/chest.129.5.1155.

    Article  PubMed  Google Scholar 

Download references

Funding

This was supported by a grant (2017ER620101#) by the Research of Korea Centers for Disease Control and Prevention.

Author information

Authors and Affiliations

  1. Department of Neurology, Chonnam National University Hospital, Gwangju, South Korea

    Joon-Tae Kim, Man-Seok Park, Kang-Ho Choi & Ki-Hyun Cho

  2. Clinical Research Center, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

    Ji Sung Lee

  3. Department of Neurology, Seoul National University College of Medicine, Cerebrovascular Center, Seoul National University Bundang Hospital, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, South Korea

    Beom Joon Kim & Hee-Joon Bae

  4. Department of Neurology, Nowon Eulji Medical Center, Eulji University, Seoul, South Korea

    Jong-Moo Park & Kyusik Kang

  5. Department of Neurology, Eulji University Hospital, Eulji University, Daejeon, South Korea

    Soo Joo Lee & Jae Guk Kim

  6. Department of Neurology, Dong-A University Hospital, Busan, South Korea

    Jae-Kwan Cha & Dae-Hyun Kim

  7. Department of Neurology, Seoul Medical Center, Seoul, South Korea

    Tai Hwan Park & Sang-Soon Park

  8. Department of Neurology, Soonchunhyang University Hospital, Seoul, South Korea

    Kyung Bok Lee

  9. Department of Neurology, Yeungnam University Hospital, Daegu, South Korea

    Jun Lee

  10. Department of Neurology, Ilsan Paik Hospital, Inje University, Goyang, South Korea

    Keun-Sik Hong, Yong-Jin Cho & Hong-Kyun Park

  11. Department of Neurology, Hallym Neurological Institute, Hallym University Sacred Heart Hospital, Anyang, South Korea

    Byung-Chul Lee, Kyung-Ho Yu & Mi Sun Oh

  12. Department of Neurology, Dongguk University Ilsan Hospital, Goyang, South Korea

    Dong-Eog Kim & Wi-Sun Ryu

  13. Department of Neurology, Jeju National University Hospital, Jeju National University School of Medicine, Jeju, South Korea

    Jay Chol Choi

  14. Department of Neurology, Ulsan University College of Medicine, Ulsan, South Korea

    Jee-Hyun Kwon & Wook-Joo Kim

  15. Department of Neurology, Chungbuk National University Hospital, Cheongju, South Korea

    Dong-Ick Shin

  16. Department of Neurology, Keimyung University Dongsan Medical Center, Daegu, South Korea

    Sung Il Sohn & Jeong-Ho Hong

  17. Department of Biostatistics, Korea University College of Medicine, Seoul, South Korea

    Juneyoung Lee

  18. Department of Neurology, Northwestern Feinberg School of Medicine, Chicago, IL, USA

    Philip B. Gorelick

  19. Department of Translational Neuroscience, Michigan State University College of Human Medicine, Grand Rapids, MI, USA

    Philip B. Gorelick

Authors
  1. Joon-Tae Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ji Sung Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Beom Joon Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jong-Moo Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kyusik Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Soo Joo Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jae Guk Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jae-Kwan Cha
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Dae-Hyun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Tai Hwan Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Sang-Soon Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Kyung Bok Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Jun Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Keun-Sik Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Yong-Jin Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Hong-Kyun Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Byung-Chul Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Kyung-Ho Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Mi Sun Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Dong-Eog Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Wi-Sun Ryu
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Jay Chol Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Jee-Hyun Kwon
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Wook-Joo Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Dong-Ick Shin
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Sung Il Sohn
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Jeong-Ho Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. Man-Seok Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  29. Kang-Ho Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  30. Ki-Hyun Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  31. Juneyoung Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  32. Philip B. Gorelick
    View author publications

    You can also search for this author in PubMed Google Scholar

  33. Hee-Joon Bae
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Joon-Tae Kim or Hee-Joon Bae.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflicts of interest.

Disclosures

H.-J.B is involved in the principal investigation, a member of the steering committee, and/or a site investigator of multicenter clinical trials or clinical studies sponsored by Otsuka Korea, Bayer, Boehringer Ingelheim, Handok Pharmaceutical Company, SK Chemicals, Pfizer, ESAI-Korea, Daewoong Pharmaceutical Co. Ltd., Daiichi Sankyo, AstraZeneca Korea, Dong-A Pharmaceutical, Yuhan Corporation, BMS Korea, Korean Drug Co., Ltd., Servier, Shire Korea Ltd., and Shin Poong Pharm. Co. Ltd.; served on the scientific advisory board for Amgen Asia Holding Limited; served as the consultant for Celltrion, Inc. and Korean Drug Co., Ltd.; and received lecture honoraria from Daiichi Sankyo Korea, Otsuka Korea, Esai Korea, Korean Drug Co., Ltd., and Shire Korea Ltd. (modest). PBG serves as a member of the ARRIVE Steering Committee for Bayer (modest).

Ethics Approval

The current study was approved by the local institutional review boards at all participating centers, including the Chonnam National University Hospital.

Consent to Participate

The requirement for a written informed consent from the study subjects was waived based on maintenance of study subject anonymity and minimal risk to the participants.

Consent to Publication

Not applicable.

Code Availability

Not applicable.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic Supplementary Material

ESM 1

(DOCX 439 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, JT., Lee, J.S., Kim, B.J. et al. Effectiveness of Adding Antiplatelets to Oral Anticoagulants in Patients with Acute Ischemic Stroke with Atrial Fibrillation and Concomitant Large Artery Steno-Occlusion. Transl. Stroke Res. 11, 1322–1331 (2020). https://doi.org/10.1007/s12975-020-00822-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12975-020-00822-z

Keywords

Search

Navigation