Skip to main content

Advertisement

Springer Nature Link
Log in

COVID-19 Diagnosis, Oral Anticoagulation, and Stroke Risk in Patients with Atrial Fibrillation

  • Original Research Article
  • Published:
American Journal of Cardiovascular Drugs Aims and scope Submit manuscript

Abstract

Background

Coronavirus disease 2019 (COVID-19) has been associated with an increased risk of stroke. It remains unclear whether the risk of stroke associated with a diagnosis of COVID-19 differed with oral anticoagulation (OAC) use. The aim of this study was to evaluate the association between COVID-19 infection, OAC use, and stroke in patients with atrial fibrillation (AF).

Methods

A retrospective cohort study was conducted in individuals with established AF using data from Optum’s deidentified Clinformatics® Data Mart Database. Cox proportional hazard models with time-dependent variables were employed to assess the association between possession of OAC, COVID-19 diagnosis in both inpatient and outpatient setting, and time to ischemic stroke.

Results

A total of 561,758 individuals aged 77 ± 10 were included in the study, with a mean follow up time of 1.3 years. OAC use was associated with a reduced stroke risk [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.82–0.88]. COVID-19 infection was associated with an increased risk of stroke (HR 2.11, 95% CI 1.87–2.38); this increased risk was particularly pronounced for patients diagnosed with an inpatient diagnosis of COVID-19 (HR 3.95, 95% CI 3.33–4.68). There was no significant interaction between OAC use and COVID-19 diagnosis (p value = 0.96). As a result, the relative increase in stroke risk associated with COVID-19 did not differ between patients on OAC (HR 2.12; 95% CI 1.71–2.62) and those not on OAC (HR 2.11; 95% CI 1.83–2.43).

Conclusion

In a nationwide sample of patients with established AF, we found the relative increase in stroke risk associated with COVID-19 was independent of OAC use.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Explore related subjects

Discover the latest articles and news from researchers in related subjects, suggested using machine learning.

References

  1. Cui Y, Zhao B, Li T, Yang Z, Li S, Le W. Risk of ischemic stroke in patients with COVID-19 infection: a systematic review and meta-analysis. Brain Res Bull. 2022;180:31–7. https://doi.org/10.1016/j.brainresbull.2021.12.011.

    Article  CAS  PubMed  Google Scholar 

  2. Massoud GP, Hazimeh DH, Amin G, Mekary W, Khabsa J, Araji T, Fares S, Mericskay M, Booz GW, Zouein FA. Risk of thromboembolic events in non-hospitalized COVID-19 patients: a systematic review. Eur J Pharmacol. 2023;941: 175501. https://doi.org/10.1016/j.ejphar.2023.175501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Ramacciotti E, Barile Agati L, Calderaro D, Aguiar VCR, Spyropoulos AC, de Oliveira CCC, Lins dos Santos J, Volpiani GG, Sobreira ML, Joviliano EE, et al. Rivaroxaban versus no anticoagulation for post-discharge thromboprophylaxis after hospitalisation for COVID-19 (MICHELLE): an open-label, multicentre, randomised, controlled trial. Lancet. 2022;399:50–9. https://doi.org/10.1016/S0140-6736(21)02392-8.

    Article  CAS  PubMed  Google Scholar 

  4. Lopes RD, DeBarros ESPGM, Furtado RHM, Macedo AVS, Ramacciotti E, Damini LP, Bronhara B, Cavalcanti AB, Rosa RG, Azevedo LCP, et al. Randomized clinical trial to evaluate a routine full anticoagulation strategy in patients with coronavirus infection (SARS-CoV2) admitted to hospital: rationale and design of the ACTION (anticoagulation coronavirus)-coalition IV trial. Am Heart J. 2021;238:1–11. https://doi.org/10.1016/j.ahj.2021.04.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Raatikainen P, Lassila R. COVID-19: another reason for anticoagulation in patients with atrial fibrillation. Heart. 2022;108:902–4. https://doi.org/10.1136/heartjnl-2022-320845.

    Article  CAS  PubMed  Google Scholar 

  6. Romiti GF, Corica B, Lip GYH, Proietti M. Prevalence and impact of atrial fibrillation in hospitalized patients with COVID-19: a systematic review and meta-analysis. J Clin Med. 2021;10:2490.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ageno W, De Candia E, Iacoviello L, Di Castelnuovo A. Protective effect of oral anticoagulant drugs in atrial fibrillation patients admitted for COVID-19: Results from the CORIST study. Thromb Res. 2021;203:138–41. https://doi.org/10.1016/j.thromres.2021.05.006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Fumagalli S, Trevisan C, Del Signore S, Pelagalli G, Volpato S, Gareri P, Mossello E, Malara A, Monzani F, Coin A, et al. COVID-19 and atrial fibrillation in older patients: does oral anticoagulant therapy provide a survival benefit?—an insight from the GeroCovid registry. Thromb Haemost. 2021;122:105–12. https://doi.org/10.1055/a-1503-3875.

    Article  PubMed  Google Scholar 

  9. Handy A, Banerjee A, Wood AM, Dale C, Sudlow CLM, Tomlinson C, Bean D, Thygesen JH, Mizani MA, Katsoulis M, et al. Evaluation of antithrombotic use and COVID-19 outcomes in a nationwide atrial fibrillation cohort. Heart. 2022;108:923–31. https://doi.org/10.1136/heartjnl-2021-320325.

    Article  CAS  PubMed  Google Scholar 

  10. Louis D, Kennedy K, Saad M, Salber G, Imran Hafiz M, Wark T, Soares C, Ghosalkar D, Cherala R, Poppas A, et al. Pre-admission oral anticoagulation is associated with fewer thrombotic complications in patients admitted with covid-19. J Am Coll Cardiol. 2022;79:1798–1798. https://doi.org/10.1016/S0735-1097(22)02789-9.

    Article  CAS  PubMed Central  Google Scholar 

  11. Hernandez I, Yang L, Tang S, Cameron T, Guo J, Gabriel N, Essien UR, Magnani JW, Gellad WF. COVID-19 pandemic and trends in clinical outcomes and medication use for patients with established atrial fibrillation: a nationwide analysis of claims data. Am Heart J Plus Cardiol Res Practice. 2024;42: 100396. https://doi.org/10.1016/j.ahjo.2024.100396.

    Article  Google Scholar 

  12. Service CfMaM. Chronic conditions data warehouse data dictionaries; 2020. https://www2.ccwdata.org/web/guest/data-dictionaries. Accessed December 2016.

  13. January CT, Wann LS, Calkins H, Chen LY, Cigarroa JE, Cleveland JC Jr, Ellinor PT, Ezekowitz MD, Field ME, Furie KL, et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines and the heart rhythm society. J Am Coll Cardiol. 2019;74:104–32. https://doi.org/10.1016/j.jacc.2019.01.011.

    Article  PubMed  Google Scholar 

  14. Newman TV, Chen N, He M, Saba S, Hernandez I. Effectiveness and safety of restarting oral anticoagulation in patients with atrial fibrillation after an intracranial hemorrhage: analysis of medicare part D claims data from 2010–2016. Am J Cardiovasc Drugs. 2020;20:471–9. https://doi.org/10.1007/s40256-019-00388-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Hernandez I, He M, Guo J, Tadrous M, Gabriel N, Swabe G, Gellad WF, Essien UR, Saba S, Benjamin EJ, et al. COVID-19 pandemic and trends in new diagnosis of atrial fibrillation: a nationwide analysis of claims data. PLoS ONE. 2023;18: e0281068. https://doi.org/10.1371/journal.pone.0281068.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Tirschwell DL, Longstreth WT Jr. Validating administrative data in stroke research. Stroke. 2002;33:2465–70. https://doi.org/10.1161/01.str.0000032240.28636.bd.

    Article  PubMed  Google Scholar 

  17. Prevention CfDCa. New ICD-10-CM code for the 2019 novel coronavirus (COVID-19); 2020. https://www.cdc.gov/nchs/data/icd/Announcement-New-ICD-code-for-coronavirus-3-18-2020.pdf. Accessed April 2022.

  18. Yang L, Tang S, He M, Guo J, Gabriel N, Swabe G, Gellad WF, Essien UR, Saba S, Benjamin EJ, et al. COVID-19 pandemic and initiation of treatment for atrial fibrillation: a nationwide analysis of claims data. BMC Cardiovasc Disord. 2023;23:604. https://doi.org/10.1186/s12872-023-03614-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Yang L, Guo J, Liang Q, Newman TV, Gellad WF, Hernandez I. Primary care provider payment models and adherence to anticoagulation in patients with atrial fibrillation. J Manage Care Spec Pharm. 2021;27:1672–9. https://doi.org/10.18553/jmcp.2021.27.12.1672.

    Article  Google Scholar 

  20. Hernandez I, He M, Chen N, Brooks MM, Saba S, Gellad WF. Trajectories of oral anticoagulation adherence among medicare beneficiaries newly diagnosed with atrial fibrillation. J Am Heart Assoc. 2019;8: e011427. https://doi.org/10.1161/JAHA.118.011427.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Hernandez I, He M, Brooks MM, Saba S, Gellad WF. Adherence to anticoagulation and risk of stroke among medicare beneficiaries newly diagnosed with atrial fibrillation. Am J Cardiovasc Drugs. 2020;20:199–207. https://doi.org/10.1007/s40256-019-00371-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Newman TV, Gabriel N, Liang Q, Drake C, El Khoudary SR, Good CB, Gellad WF, Hernandez I. Comparison of oral anticoagulation use and adherence among Medicare beneficiaries enrolled in stand-alone prescription drug plans vs medicare advantage prescription drug plans. J Manage Care Spec Pharm. 2022;28:266–74. https://doi.org/10.18553/jmcp.2022.28.2.266.

    Article  Google Scholar 

  23. Chen N, Brooks MM, Hernandez I. Latent classes of adherence to oral anticoagulation therapy among patients with a new diagnosis of atrial fibrillation. JAMA Netw Open. 2020;3:e1921357–e1921357. https://doi.org/10.1001/jamanetworkopen.2019.21357.

    Article  PubMed  PubMed Central  Google Scholar 

  24. DeFrank JT, Bowling JM, Rimer BK, Gierisch JM, Skinner CS. Triangulating differential nonresponse by race in a telephone survey. Prev Chron Dis. 2007;4:A60.

    Google Scholar 

  25. Joundi Raed A, Cipriano Lauren E, Sposato Luciano A, Saposnik G. Ischemic stroke risk in patients with atrial fibrillation and CHA2DS2-VASc score of 1. Stroke. 2016;47:1364–7. https://doi.org/10.1161/STROKEAHA.115.012609.

    Article  CAS  PubMed  Google Scholar 

  26. Zhu W, He W, Guo L, Wang X, Hong K. The HAS-BLED score for predicting major bleeding risk in anticoagulated patients with atrial fibrillation: a systematic review and meta-analysis. Clin Cardiol. 2015;38:555–61. https://doi.org/10.1002/clc.22435.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Yang L, Brooks M, Glynn N, Zhang Y, Saba S, Hernandez I. Real-world direct comparison of the effectiveness and safety of apixaban, dabigatran, rivaroxaban, and warfarin in medicare beneficiaries with atrial fibrillation. Am J Cardiol. 2020;126:29–36. https://doi.org/10.1016/j.amjcard.2020.03.034.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Hernandez I, Zhang Y, Saba S. Comparison of the effectiveness and safety of apixaban, dabigatran, rivaroxaban, and warfarin in newly diagnosed atrial fibrillation. Am J Cardiol. 2017;120:1813–9. https://doi.org/10.1016/j.amjcard.2017.07.092.

    Article  CAS  PubMed  Google Scholar 

  29. Stefanou Ε, Karvelas N, Bennett S, Kole C. Cerebrovascular manifestations of SARS-CoV-2: A comprehensive review. Curr Treat Opt Neurol. 2023;25:71–92. https://doi.org/10.1007/s11940-023-00747-6.

    Article  Google Scholar 

  30. Tan YK, Goh C, Leow AST, Tambyah PA, Ang A, Yap ES, Tu TM, Sharma VK, Yeo LLL, Chan BPL, et al. COVID-19 and ischemic stroke: a systematic review and meta-summary of the literature. J Thromb Thrombolysis. 2020;50:587–95. https://doi.org/10.1007/s11239-020-02228-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kim Y, Parekh MA, Li X, Huang Y, Zhang G-Q, Manwani B. Age and sex-specific stroke epidemiology in COVID-19. Front Stroke. 2023. https://doi.org/10.3389/fstro.2023.1172854.

    Article  Google Scholar 

  32. Hanff TC, Mohareb AM, Giri J, Cohen JB, Chirinos JA. Thrombosis in COVID-19. Am J Hematol. 2020;95:1578–89. https://doi.org/10.1002/ajh.25982.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Guo Y, Lip GYH, Apostolakis S. Inflammation in atrial fibrillation. J Am Coll Cardiol. 2012;60:2263–70. https://doi.org/10.1016/j.jacc.2012.04.063.

    Article  CAS  PubMed  Google Scholar 

  34. Gawałko M, Kapłon-Cieślicka A, Hohl M, Dobrev D, Linz D. COVID-19 associated atrial fibrillation: incidence, putative mechanisms and potential clinical implications. Int J Cardiol Heart Vasc. 2020;30: 100631. https://doi.org/10.1016/j.ijcha.2020.100631.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Wong AY, Tomlinson L, Brown JP, Elson W, Walker AJ, Schultze A, Morton CE, Evans D, Inglesby P, MacKenna B, et al. Association between oral anticoagulants and COVID-19-related outcomes: a population-based cohort study. Br J Gen Pract. 2022;72:e456–63. https://doi.org/10.3399/bjgp.2021.0689.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Louis DW, Kennedy KF, Saad M, Salber G, Imran H, Wark T, Soares C, Ghosalkar D, Cherala R, Poppas A, et al. Preadmission oral anticoagulation for atrial fibrillation/flutter and death or thrombotic events during COVID-19 admission. Am J Cardiol. 2022;181:38–44. https://doi.org/10.1016/j.amjcard.2022.07.006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Rekk K, Arnet I, Dietrich F, Polymeris AA, Lyrer PA, Engelter ST, Schaedelin S, Allemann SS. Relationship between electronically monitored adherence to direct oral anticoagulants and ischemic or hemorrhagic events after an initial ischemic stroke—a case control study. PLoS ONE. 2024;19: e0301421. https://doi.org/10.1371/journal.pone.0301421.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Clinical Pharmacy, University of California San Diego, Skaggs School of Pharmacy and Pharmaceutical Sciences, 9500 Gilman Dr, Room 2244, La Jolla, CA, 92093, USA

    Lanting Yang, Shangbin Tang, Nico Gabriel & Inmaculada Hernandez

  2. Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, FL, USA

    Jingchuan Guo

  3. Division of General Internal Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Walid F. Gellad

  4. Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA

    Walid F. Gellad

  5. Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

    Utibe R. Essien

  6. Center for the Study of Healthcare Innovation, Implementation and Policy, Greater Los Angeles VA Healthcare System, Los Angeles, CA, USA

    Utibe R. Essien

  7. Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Jared W. Magnani

Authors
  1. Lanting Yang
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Shangbin Tang
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Jingchuan Guo
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Nico Gabriel
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Walid F. Gellad
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Utibe R. Essien
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Jared W. Magnani
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Inmaculada Hernandez
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to Inmaculada Hernandez.

Ethics declarations

Funding

This work was funded by the National Heart, Lung and Blood Institute (grants K01HL142847 and R01HL15705). Dr. Magnani is funded by R01HL160749 and K24HL160527. Dr. Guo is funded by NIDDK R01DK133465 and PhRMA Foundation Research Starter Award. The funders had no role in design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication.

Competing Interests

Inmaculada Hernandez has received consulting fees from Pfizer and Bristol Myers Squibb, outside of the submitted work. Lanting Yang, Shangbin Tang, Jingchuan Guo, Nico Gabriel, Walid F Gellad, Utibe R. Essien, and Jared W. Magnani no competing interests to declare.

Author Contributions

L.Y. carried out conceptualization, data curation, analysis, methodology and writing. S.T. carried out data curation, analysis, methodology, reviewing, and editing. J.G. carried out the investigation, methodology, validation, and reviewing and editing. N.G. carried out and planned the methodology, data curation, validation, and reviewing and editing. W.F.G. carried out the investigation, supervision, validation, and reviewing and editing. U.R.E. carried out the investigation, supervision, validation, and reviewing and editing. J.W.M. carried out the investigation, supervision, validation, and reviewing and editing. I.H. carried out the conceptualization, methodology, investigation, supervision, writing, and reviewing and editing.

Data Availability Statement

The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Ethics Approval

The Institutional Review Board at the University of California, San Diego approved this study as exempt as deidentified data were used in analyses.

Code Availability

Not applicable.

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 374 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, L., Tang, S., Guo, J. et al. COVID-19 Diagnosis, Oral Anticoagulation, and Stroke Risk in Patients with Atrial Fibrillation. Am J Cardiovasc Drugs 24, 693–702 (2024). https://doi.org/10.1007/s40256-024-00671-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40256-024-00671-3

Profiles

  1. Lanting Yang View author profile
  2. Inmaculada Hernandez View author profile