Skip to main content
SpringerLink
Log in

Warfarin therapy and incidence of cerebrovascular complications in left-sided native valve endocarditis

  • Article
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

Anticoagulant therapy has been anticipated to increase the risk of cerebrovascular complications (CVC) in native valve endocarditis (NVE). This study investigates the relationship between ongoing oral anticoagulant therapy and the incidence of symptomatic CVC in left-sided NVE. In a prospective cohort study, the CVC incidence was compared between NVE patients with and without ongoing warfarin. Among 587 NVE episodes, 48 (8%) occurred in patients on warfarin. A symptomatic CVC was seen in 144 (25%) patients, with only three on warfarin. CVC were significantly less frequent in patients on warfarin (6% vs. 26%, odds ratio [OR] 0.20, 95% confidence interval [CI] 0.06–0.6, p = 0.006). No increase in haemorrhagic lesions was detected in patients on warfarin. Staphylococcus aureus aetiology (adjusted OR [aOR] 6.3, 95% CI 3.8–10.4) and vegetation length (aOR 1.04, 96% CI 1.01–1.07) were risk factors for CVC, while warfarin on admission (aOR 0.26, 95% CI 0.07–0.94), history of congestive heart failure (adjusted OR 0.22, 95% CI 0.1–0.52) and previous endocarditis (aOR 0.1, 95% CI 0.01–0.79) correlated with lower CVC frequency.

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

References

  1. Priest WS, Smith JM, McGee CJ (1946) The effect of anticoagulants on the penicillin therapy and the pathologic lesion of subacute bacterial endocarditis. N Engl J Med 235:699–706

    Article  CAS  PubMed  Google Scholar 

  2. Loewe L (1945) The combined use of anti-infectives and anticoagulants in the treatment of subacute bacterial endocarditis. Bull N Y Acad Med 21(2):59–86

    CAS  PubMed  Google Scholar 

  3. Cates JE, Christie RV (1951) Subacute bacterial endocarditis: a review of 442 patients treated in 14 centres appointed by the Penicillin Trials Committee of the Medical Research Council. Q J Med 20:93–130

    Google Scholar 

  4. Finland M (1958) Current status of therapy in bacterial endocarditis. J Am Med Assoc 166(4):364–373

    CAS  PubMed  Google Scholar 

  5. Pruitt AA, Rubin RH, Karchmer AW, Duncan GW (1978) Neurologic complications of bacterial endocarditis. Medicine (Baltimore) 57(4):329–343

    CAS  Google Scholar 

  6. Delahaye JP, Poncet P, Malquarti V, Beaune J, Garé JP, Mann JM (1990) Cerebrovascular accidents in infective endocarditis: role of anticoagulation. Eur Heart J 11(12):1074–1078

    CAS  PubMed  Google Scholar 

  7. Habib G, Hoen B, Tornos P, Thuny F, Prendergast B, Vilacosta I, Moreillon P, de Jesus Antunes M, Thilen U, Lekakis J, Lengyel M, Müller L, Naber CK, Nihoyannopoulos P, Moritz A, Zamorano JL, Vahanian A, Auricchio A, Bax J, Ceconi C, Dean V, Filippatos G, Funck-Brentano C, Hobbs R, Kearney P, McDonagh T, McGregor K, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Vardas P, Widimsky P (2009) Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009): the Task Force on the Prevention, Diagnosis, and Treatment of Infective Endocarditis of the European Society of Cardiology (ESC). Eur Heart J 30(19):2369–2413

    Article  PubMed  Google Scholar 

  8. Baddour LM, Wilson WR, Bayer AS, Fowler VG Jr, Bolger AF, Levison ME, Ferrieri P, Gerber MA, Tani LY, Gewitz MH, Tong DC, Steckelberg JM, Baltimore RS, Shulman ST, Burns JC, Falace DA, Newburger JW, Pallasch TJ, Takahashi M, Taubert KA (2005) Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation 111(23):e394–e434

    Article  PubMed  Google Scholar 

  9. Westling K, Aufwerber E, Ekdahl C, Friman G, Gårdlund B, Julander I, Olaison L, Olesund C, Rundström H, Snygg-Martin U, Thalme A, Werner M, Hogevik H (2007) Swedish guidelines for diagnosis and treatment of infective endocarditis. Scand J Infect Dis 39(11–12):929–946

    Article  PubMed  Google Scholar 

  10. Tornos P, Almirante B, Mirabet S, Permanyer G, Pahissa A, Soler-Soler J (1999) Infective endocarditis due to Staphylococcus aureus: deleterious effect of anticoagulant therapy. Arch Intern Med 159(5):473–475

    Article  CAS  PubMed  Google Scholar 

  11. Wilson WR, Geraci JE, Danielson GK, Thompson RL, Spittell JA Jr, Washington JR 2nd, Giuliani ER (1978) Anticoagulant therapy and central nervous system complications in patients with prosthetic valve endocarditis. Circulation 57(5):1004–1007

    CAS  PubMed  Google Scholar 

  12. Karchmer AW, Dismukes WE, Buckley MJ, Austen WG (1978) Late prosthetic valve endocarditis: clinical features influencing therapy. Am J Med 64(2):199–206

    Article  CAS  PubMed  Google Scholar 

  13. Ruttmann E, Willeit J, Ulmer H, Chevtchik O, Höfer D, Poewe W, Laufer G, Müller LC (2006) Neurological outcome of septic cardioembolic stroke after infective endocarditis. Stroke 37(8):2094–2099

    Article  PubMed  Google Scholar 

  14. Snygg-Martin U, Gustafsson L, Rosengren L, Alsiö A, Ackerholm P, Andersson R, Olaison L (2008) Cerebrovascular complications in patients with left-sided infective endocarditis are common: a prospective study using magnetic resonance imaging and neurochemical brain damage markers. Clin Infect Dis 47(1):23–30

    Article  PubMed  Google Scholar 

  15. Thuny F, Avierinos JF, Tribouilloy C, Giorgi R, Casalta JP, Milandre L, Brahim A, Nadji G, Riberi A, Collart F, Renard S, Raoult D, Habib G (2007) Impact of cerebrovascular complications on mortality and neurologic outcome during infective endocarditis: a prospective multicentre study. Eur Heart J 28(9):1155–1161

    Article  PubMed  Google Scholar 

  16. Hart RG, Kagan-Hallet K, Joerns SE (1987) Mechanisms of intracranial hemorrhage in infective endocarditis. Stroke 18(6):1048–1056

    CAS  PubMed  Google Scholar 

  17. Thompson J, Meddens MJ, Thörig L, van Furth R (1982) The role of bacterial adherence in the pathogenesis of infective endocarditis. Infection 10(3):196–198

    Article  CAS  PubMed  Google Scholar 

  18. Kroh HK, Panizzi P, Bock PE (2009) Von Willebrand factor-binding protein is a hysteretic conformational activator of prothrombin. Proc Natl Acad Sci USA 106(19):7786–7791

    Article  CAS  PubMed  Google Scholar 

  19. Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, Singer DE (2001) Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 285(18):2370–2375

    Article  CAS  PubMed  Google Scholar 

  20. Leport C, Vilde JL, Bricaire F, Cohen A, Pangon B, Gaudebout C, Valere PE (1987) Fifty cases of late prosthetic valve endocarditis: improvement in prognosis over a 15 year period. Br Heart J 58(1):66–71

    Article  CAS  PubMed  Google Scholar 

  21. Flaherty ML, Kissela B, Woo D, Kleindorfer D, Alwell K, Sekar P, Moomaw CJ, Haverbusch M, Broderick JP (2007) The increasing incidence of anticoagulant-associated intracerebral hemorrhage. Neurology 68(2):116–121

    Article  CAS  PubMed  Google Scholar 

  22. Heiro M, Nikoskelainen J, Engblom E, Kotilainen E, Marttila R, Kotilainen P (2000) Neurologic manifestations of infective endocarditis: a 17-year experience in a teaching hospital in Finland. Arch Intern Med 160(18):2781–2787

    Article  CAS  PubMed  Google Scholar 

  23. Dickerman SA, Abrutyn E, Barsic B, Bouza E, Cecchi E, Moreno A, Doco-Lecompte T, Eisen DP, Fortes CQ, Fowler VG Jr, Lerakis S, Miro JM, Pappas P, Peterson GE, Rubinstein E, Sexton DJ, Suter F, Tornos P, Verhagen DW, Cabell CH (2007) The relationship between the initiation of antimicrobial therapy and the incidence of stroke in infective endocarditis: an analysis from the ICE Prospective Cohort Study (ICE-PCS). Am Heart J 154(6):1086–1094

    Article  CAS  PubMed  Google Scholar 

  24. Le Cam B, Guivarch G, Boles JM, Garre M, Cartier F (1984) Neurologic complications in a group of 86 bacterial endocarditis. Eur Heart J 5(Suppl C):97–100

    PubMed  Google Scholar 

  25. Cooper HA, Thompson EC, Laureno R, Fuisz A, Mark AS, Lin M, Goldstein SA (2009) Subclinical brain embolization in left-sided infective endocarditis: results from the evaluation by MRI of the brains of patients with left-sided intracardiac solid masses (EMBOLISM) pilot study. Circulation 120(7):585–591

    Article  PubMed  Google Scholar 

  26. Toone CE Jr (1941) Cerebral manifestations of bacterial endocarditis. Ann Intern Med 14:1551–1574

    Google Scholar 

  27. Jones HR Jr, Siekert RG (1989) Neurological manifestations of infective endocarditis. Review of clinical and therapeutic challenges. Brain 112(Pt 5):1295–1315

    Article  PubMed  Google Scholar 

  28. Bitsch A, Nau R, Hilgers RA, Verheggen R, Werner G, Prange HW (1996) Focal neurologic deficits in infective endocarditis and other septic diseases. Acta Neurol Scand 94(4):279–286

    Article  CAS  PubMed  Google Scholar 

  29. Thuny F, Di Salvo G, Belliard O, Avierinos JF, Pergola V, Rosenberg V, Casalta JP, Gouvernet J, Derumeaux G, Iarussi D, Ambrosi P, Calabró R, Riberi A, Collart F, Metras D, Lepidi H, Raoult D, Harle JR, Weiller PJ, Cohen A, Habib G (2005) Risk of embolism and death in infective endocarditis: prognostic value of echocardiography: a prospective multicenter study. Circulation 112(1):69–75

    Article  PubMed  Google Scholar 

  30. Durante Mangoni E, Adinolfi LE, Tripodi MF, Andreana A, Gambardella M, Ragone E, Precone DF, Utili R, Ruggiero G (2003) Risk factors for “major” embolic events in hospitalized patients with infective endocarditis. Am Heart J 146(2):311–316

    Article  PubMed  Google Scholar 

  31. Rasmussen RV, Snygg-Martin U, Olaison L, Buchholtz K, Larsen CT, Hassager C, Bruun NE (2009) Major cerebral events in Staphylococcus aureus infective endocarditis: is anticoagulant therapy safe? Cardiology 114(4):284–291

    Article  PubMed  Google Scholar 

  32. Olaison L, Hogevik H, Myken P, Oden A, Alestig K (1996) Early surgery in infective endocarditis. QJM 89(4):267–278

    CAS  PubMed  Google Scholar 

  33. Murdoch DR, Corey GR, Hoen B, Miró JM, Fowler VG Jr, Bayer AS, Karchmer AW, Olaison L, Pappas PA, Moreillon P, Chambers ST, Chu VH, Falcó V, Holland DJ, Jones P, Klein JL, Raymond NJ, Read KM, Tripodi MF, Utili R, Wang A, Woods CW, Cabell CH (2009) Clinical presentation, etiology, and outcome of infective endocarditis in the 21st century: the International Collaboration on Endocarditis—Prospective Cohort Study. Arch Intern Med 169(5):463–473

    Article  PubMed  Google Scholar 

Download references

Acknowledgement

We thank Salmir Nasic of the Research and Development Centre, Skaraborg Hospital, Sweden, for the assistance with the statistical analyses.

Author information

Authors and Affiliations

  1. Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden

    U. Snygg-Martin, R. Andersson & L. Olaison

  2. Research and Development Centre, Skaraborg Hospital, Skövde, Sweden

    R. Andersson

  3. Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark

    R. V. Rasmussen & N. E. Bruun

  4. Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

    C. Hassager

  5. Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska University Hospital, 416 85, Gothenburg, Sweden

    U. Snygg-Martin

Authors
  1. U. Snygg-Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. V. Rasmussen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Hassager
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N. E. Bruun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R. Andersson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. L. Olaison
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to U. Snygg-Martin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Snygg-Martin, U., Rasmussen, R.V., Hassager, C. et al. Warfarin therapy and incidence of cerebrovascular complications in left-sided native valve endocarditis. Eur J Clin Microbiol Infect Dis 30, 151–157 (2011). https://doi.org/10.1007/s10096-010-1063-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-010-1063-3

Keywords

Search

Navigation