Skip to main content

Advertisement

Log in

Epidemiology and secondary prevention of ischemic stroke in patients on antiplatelet drug: a retrospective cohort study

  • Published:
Journal of Thrombosis and Thrombolysis Aims and scope Submit manuscript

Abstract

One-third to one-half of ischemic strokes occurred in patients taking antiplatelet drugs. The optimal therapeutic strategy for antithrombotic drugs remains uncertain and guidelines provide scarse recommendation. Therefore, aims of our study were to: (i) estimate the prevalence of patients who develop an ischemic stroke while on antiplatelet drugs, (ii) investigate potential factors associated with this phenomenon, (iii) describe management strategies in daily clinical practice. Consecutive adult patients admitted for acute ischemic stroke at the academic hospital of Varese, Italy, from January 2010 till December 2011 were included. Patients were retrospectively identified by searching the administrative database of the hospital. Odds ratios (ORs) and their 95% confidence intervals (CI) for identifying factors associated with dependent variable were estimated using univariate logistic regression. Any variable with a p value < 0.2 at univariate analysis was included in a multivariate model. A total of 419 patients were included. Patients with ischemic stroke while on antiplatelet drugs were 49.6%. The following baseline characteristics were associated with the occurrence of ischemic stroke in patients taking antiplatelet drugs: diabetes mellitus (DM), history of ischemic heart disease (IHD), age > 65 years and previous stroke or transient ischemic stroke (TIA). The following variables were significantly associated with a change of antithrombotic therapy at discharge: DM, history of IHD and previous stroke or TIA. Our study confirms that the occurrence of ischemic stroke during antiplatelet treatment is common and management of antithrombotic therapy is heterogeneous. Factors that may explain therapeutic failure include undetected cardioembolic sources, drug resistance, poor compliance, or the presence of diabetes, atherothrombotic disease, and advanced age. Randomized controlled trials are warranted to assess the optimal antithrombotic strategy for ischemic stroke occurred in patients taking antiplatelet drugs.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, American Heart Association Stroke Council et al (2018) Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 49(2018):e46–e110

    Google Scholar 

  2. Antiplatelet Trialists’ Collaboration (1988) Secondary prevention of vascular disease by prolonged antiplatelet treatment. Br Med J 296:320–331

    Article  Google Scholar 

  3. Buring J, Hennekens C, Kearney P, Meade T, Patrono C, Roncaglioni MC, Antithrombotic Trialists’ (ATT) Collaboration et al (2009) Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 373:1849–1860

    Article  CAS  PubMed  Google Scholar 

  4. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, American Heart Association Statistics Committee and Stroke Statistics Subcommittee et al (2013) Executive summary: heart disease and stroke statistics–2013 update—a report from the American Heart Association. Circulation 127:143–152

    Article  PubMed  Google Scholar 

  5. CAPRIE Steering Committee (1996) A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 348:1329–1339

    Article  Google Scholar 

  6. WHO Monica Project Principal Investigators (1988) The World Health Organization MONICA Project (monitoring trends and determinants in cardiovascular disease): a major international collaboration. J Clin Epidemiol 41:105–114

    Article  Google Scholar 

  7. Bamford J, Sandercock P, Dennis M, Burn J, Warlow C (1991) Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet 337:1521–1526

    Article  CAS  PubMed  Google Scholar 

  8. Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon Marsh DL et al (1993) Classification of subtype of acute ischemic stroke. Definition for use in a multicentre clinical trial. TOAST. Trial of Org 10172 in acute stroke treatment. Stroke 24:35–41

    Article  Google Scholar 

  9. National Institute of Health, National Institute of Neurological Disorders and Stroke. Stroke Scale. http://www.ninds.nih.gov/doctors/NIH_Stroke_Scale

  10. Touboul PJ, Hennerici MG, Meairs S, Adams H, Amarenco P, Bornstein N, Csiba L et al (2007) Mannheim carotid intima-media thickness consensus (2004-2006). An update on behalf of the Advisory Board of the 3rd and 4th Watching the Risk Symposium, 13th and 15th European Stroke Conferences, Mannheim, Germany, 2004, and Brussels, Belgium, 2006. Cerebrovasc Dis 23:75–80

    Article  PubMed  Google Scholar 

  11. Patrono C (2003) Aspirin resistance: definition, mechanisms, and clinical read-outs. J Thromb Heamost 1:1710–1713

    Article  CAS  Google Scholar 

  12. Grazioli S, Paciaroni M, Agnelli G, Acciarresi M, Alberti A, D’Amore C, Caso V, Venti M, Guasti L, Ageno W, Squizzato A (2018) Cancer-associated ischemic stroke: A retrospective multicentre cohort study. Thromb Res 165:33–37

    Article  CAS  PubMed  Google Scholar 

  13. Naderi SH, Bestwick JP, Wald DS (2012) Adherence to drugs that prevent cardiovascular disease: meta-analysis on 376,162 patients. Am J Med 125:882–887

    Article  PubMed  Google Scholar 

  14. Collet JP, Cuisset T, Rangé G, Cayla G, Elhadad S, Pouillot C et al (2012) ARCTIC Investigators, bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med 367:2100–2109

    Article  CAS  PubMed  Google Scholar 

  15. Lee M, Saver JL, Hong KS, Rao NM, Wu YL, Ovbiagele B (2017) Antiplatelet regimen for patients with breakthrough strokes while on aspirin: a systematic review and meta-analysis. Stroke 48:2610–2613

    Article  PubMed  Google Scholar 

  16. Osterberg L, Blaschke T (2005) Adherence to medication. N Engl J Med 353:487–497

    Article  CAS  Google Scholar 

  17. Engelmann B, Massberg S (2013) Thrombosis as an intravascular effector of innate immunity. Nat Rev Immunol 13:34–45

    Article  CAS  Google Scholar 

  18. Murphy AJ, Tall AR (2016) Disorder haemoatopoiesis and athero-thrombosis. Eur Heart J 37:1113–1121

    Article  PubMed  PubMed Central  Google Scholar 

  19. Doring Y, Soehnlein O, Weber C (2017) Neutrophil extracellular traps in atherosclerosis and atherothrombosis. Circ Res 120:736–743

    Article  CAS  PubMed  Google Scholar 

  20. Laridan E, Denorme F, Desender L, Francois O, Andersson T, Deckmyn H et al (2017) Neutrophil extracellular traps in ischemic stroke thrombi. Ann Neurol 82:223–232

    Article  CAS  PubMed  Google Scholar 

  21. Antithrombotic Trialists’ Collaboration (2002) Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 324:71–86

    Article  Google Scholar 

  22. Linden MD, Tran HA (2012) Overcoming aspirin treatment failure in diabetes. Crit Rev Clin Lab Sci 49:183–198

    Article  CAS  PubMed  Google Scholar 

  23. Davì G, Vazzana N, Sestili S (2012) Variability in the response to antiplatelet treatment in diabetes mellitus. Prostaglandins Other Lipid Mediat 98:48–55

    Article  CAS  PubMed  Google Scholar 

  24. Paez Espinosa EV, Murad JP, Khasawneh FT (2012) Aspirin: pharmacology and clinical applications. Thrombosis 2012:173124

    Article  CAS  PubMed  Google Scholar 

  25. Michelson AD, Cattaneo M, Eikelboom JW et al (2005) Aspirin resistance: position paper of the working group on aspirin resistance. J Thromb Haemost 3:1309–1311

    Article  CAS  PubMed  Google Scholar 

  26. Cattaneo Marco (2012) Mechanisms of variability in antiplatelet agents response. Thromb Res 130:S27–S28

    Article  PubMed  Google Scholar 

  27. Côté R, Zhang Y, Hart RG, McClure LA, Anderson DC, Talbert RL et al (2014) ASA failure: does the combination ASA/clopidogrel confer better long-term vascular protection? Neurology 82:382–389

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B et al (2016) ESC Scientific Document Group, 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 37:2893–2962

    Article  Google Scholar 

  29. Mohr JP, Thompson JL, Lazar RM, Levin B, Sacco RL, Furie KL et al (2001) Warfarin-aspirin recurrent stroke study group, A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med 345:1444–1451

    Article  CAS  PubMed  Google Scholar 

  30. Hart RG, Diener HC, Coutts SB, Easton JD, Granger CB, O’Donnell MJ et al (2014) Embolic strokes of undetermined source: the case for a new clinical construct. Cryptogenic Stroke/ESUS International Working Group, Lancet Neurol. 13:429–438

    Article  Google Scholar 

  31. Hart RG, Catanese L, Perera KS, Ntaios G, Connolly SJ (2017) embolic stroke of undetermined source: a systematic review and clinical update. Stroke 48:867–872

    Article  PubMed  Google Scholar 

  32. Hart RG, Sharma M, Mundl H, Kasner SE, Bangdiwala SI, Berkowitz SD et al (2018) NAVIGATE ESUS investigators, rivaroxaban for stroke prevention after embolic stroke of undetermined source. N Engl J Med 378:2191–2201

    Article  CAS  PubMed  Google Scholar 

  33. Furie KL, Kasner SE, Adams RJ, Albers GW, Bush RL, Fagan SC et al (2011) American Heart Association Stroke Council, Council on Cardiovascular Nursing, Council on Clinical Cardiology, and Interdisciplinary Council on Quality of Care and Outcomes Research, Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the American heart association/American stroke association. Stroke 42:227–276

    Article  PubMed  Google Scholar 

  34. Kahn S, Lim W, Dunn AS et al (2012) Prevention of VTE in non surgical patients. Chest 141(2 Suppl):e195S–e226S

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Castilla-Guerra L, Sacco RL (2014) Treating lacunar strokes occurring on aspirin: adding clopidogrel is not the simple solution. Neurology 82:376–377

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Andrea Gallo.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gallo, A., Galliazzo, S., Grazioli, S. et al. Epidemiology and secondary prevention of ischemic stroke in patients on antiplatelet drug: a retrospective cohort study. J Thromb Thrombolysis 48, 336–344 (2019). https://doi.org/10.1007/s11239-019-01893-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-019-01893-y

Keywords

Navigation