Download PDF
Thromb Haemost 2022; 122(09): 1524-1531
DOI: 10.1055/s-0042-1743473
Stroke, Systemic or Venous Thromboembolism

Adverse Events and All-Cause Mortality in Danish Patients with Cerebral Venous Thrombosis: A Nationwide Cohort Study

Anne Gulbech Ording
1   Unit for Thrombosis and Drug Research, Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark
,
Flemming Skjøth
1   Unit for Thrombosis and Drug Research, Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark
2   Unit for Clinical Biostatistics, Aalborg University Hospital, Aalborg, Denmark
,
Søren Due Andersen
3   Department of Neurology, Aalborg University Hospital, Aalborg, Denmark
,
Torben Bjerregaard Larsen
1   Unit for Thrombosis and Drug Research, Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark
› Author Affiliations Funding This study was supported by the Obel Family Foundation. The funding source played no role in in study design; the collection, analysis, or interpretation of data; writing the report; or in the decision to submit the article for publication.
› Further Information
    Permissions and Reprints

Abstract

Background Cerebral venous thrombosis (CVT) is a rare manifestation of stroke and venous thromboembolism (VTE), compared with deep vein thrombosis (DVT) and pulmonary embolism (PE). We examined whether CVT was associated with adverse cardiovascular events.

Methods A Danish cohort study with adult patients diagnosed with CVT (N = 1,015) between 1997 and 2017. We matched 10 patients with VTE (DVT and PE) to each patient with CVT for age, sex, and diagnosis year. We also matched 10 individuals from the general population to each patient with CVT. We computed cumulative incidence and estimated hazard ratios (HRs) with 95% confidence intervals (95% CIs) at 5 years for major bleeding, intracranial bleeding, ischemic stroke, and cardiovascular events. Death was examined separately.

Results Major bleeding risks were 1.2% for CVT and 0.7% for VTE at 6 months; these risks increased to 2.7% and 2.6%, respectively, at 5 years. Although rare, intracranial bleeding risks were markedly higher for CVT (2.9%) than for VTE (0.4%) at 5 years (HR = 8.9, 95% CI: 5.3–15.1). Incidences of ischemic stroke were 5.9% for CVT and 0.3% for VTE, at 6 months; and 10.0% and 1.4%, respectively, at 5 years (HR = 9.5, 95% CI: 7.1–12.7). In contrast, incidence of cardiac events was lower for CVT that VTE (1.7% vs. 3.6% at 5 years). Mortality risk was higher after CVT compared with VTE, at 6 months (6.6% vs. 3.8%), but the risks differed little at 5 years (14.3% vs. 14.1%).

Conclusion Intracranial bleeding, ischemic stroke, and mortality risks were higher for patients with CVT than matched patients with VTE and the general population, particularly within 6 months after diagnosis.

Keywords

sinuses - cerebral venous thrombosis - stroke - hemorrhage - cardiovascular events

Author Contributions

A.G.O.: Conceptualization, methodology, investigation, formal analysis, writing the original draft preparation, reviewing and editing the manuscript, and project administration. F.S.: Conceptualization, methodology, investigation, data curation, resources, formal analysis, software, validation, visualization, writing the original draft preparation, and reviewing and editing the manuscript. S.D.A.: Conceptualization, reviewing, and editing the manuscript. T.B.L.: Conceptualization, methodology, investigation, supervision, funding acquisition, resources, writing the original draft preparation, and reviewing and editing the manuscript.


Data Sharing Statement

Our approvals for using the data sources for the current study did not allow us to distribute or make patient data directly available to other parties. Interested researchers may apply for data access through the Research Service at the Danish Health Data Authority (e-mail: forskerservice@sundhedsdata.dk; phone: +45 3268 5116). Up-to-date information on data access is available online (http://sundhedsdatastyrelsen.dk/da/forskerservice). Access to data from the Danish Health Data Authority requires approval from the Danish Data Protection Agency (https://www.datatilsynet.dk/english/the-danish-data-protection-agency/introduction-to-the-danish-data-protection-agency/).


Supplementary Material



Publication History

Received: 28 May 2021

Accepted: 18 January 2022

Article published online:
10 June 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Coutinho JM, Zuurbier SM, Stam J. Declining mortality in cerebral venous thrombosis: a systematic review. Stroke 2014; 45 (05) 1338-1341
    CrossrefPubMedGoogle Scholar
  • 2 Stam J. Thrombosis of the cerebral veins and sinuses. N Engl J Med 2005; 352 (353) 791-798
    PubMedGoogle Scholar
  • 3 Bousser MG, Ferro JM. Cerebral venous thrombosis: an update. Lancet Neurol 2007; 6 (02) 162-170
    CrossrefPubMedGoogle Scholar
  • 4 Weimar C, Masuhr F, Hajjar K. Diagnosis and treatment of cerebral venous thrombosis. Expert Rev Cardiovasc Ther 2012; 10 (12) 1545-1553
    CrossrefPubMedGoogle Scholar
  • 5 Ruuskanen JO, Kytö V, Posti JP, Rautava P, Sipilä JOT. Cerebral venous thrombosis: Finnish nationwide trends. Stroke 2021; 52 (01) 335-338
    CrossrefPubMedGoogle Scholar
  • 6 Capecchi M, Abbattista M, Martinelli I. Cerebral venous sinus thrombosis. J Thromb Haemost 2018; 16 (10) 1918-1931
    CrossrefPubMedGoogle Scholar
  • 7 Bushnell C, Saposnik G. Evaluation and management of cerebral venous thrombosis. Continuum (Minneap Minn) 2014; 20 (2 Cerebrovascular Disease): 335-351
    PubMedGoogle Scholar
  • 8 Pottegård A, Lund LC, Karlstad Ø. et al. Arterial events, venous thromboembolism, thrombocytopenia, and bleeding after vaccination with Oxford-AstraZeneca ChAdOx1-S in Denmark and Norway: population based cohort study. BMJ 2021; 373 (1114): n1114
    CrossrefPubMedGoogle Scholar
  • 9 Breteau G, Mounier-Vehier F, Godefroy O. et al. Cerebral venous thrombosis 3-year clinical outcome in 55 consecutive patients. J Neurol 2003; 250 (01) 29-35
    PubMedGoogle Scholar
  • 10 Borhani Haghighi A, Edgell RC, Cruz-Flores S. et al. Mortality of cerebral venous-sinus thrombosis in a large national sample. Stroke 2012; 43 (01) 262-264
    CrossrefPubMedGoogle Scholar
  • 11 Dentali F, Gianni M, Crowther MA, Ageno W. Natural history of cerebral vein thrombosis: a systematic review. Blood 2006; 108 (04) 1129-1134
    CrossrefPubMedGoogle Scholar
  • 12 Ferro JM, Canhão P, Stam J, Bousser M-G, Barinagarrementeria F. ISCVT Investigators. Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke 2004; 35 (03) 664-670
    CrossrefPubMedGoogle Scholar
  • 13 Schaller B, Graf R. Cerebral venous infarction: the pathophysiological concept. Cerebrovasc Dis 2004; 18 (03) 179-188
    CrossrefPubMedGoogle Scholar
  • 14 Ulivi L, Squitieri M, Cohen H, Cowley P, Werring DJ. Cerebral venous thrombosis: a practical guide. Pract Neurol 2020; 20 (05) 356-367
    CrossrefPubMedGoogle Scholar
  • 15 Coutinho J, de Bruijn SF, Deveber G, Stam J. Anticoagulation for cerebral venous sinus thrombosis. Cochrane Database Syst Rev 2011; 2011 (08) CD002005
    CrossrefPubMedGoogle Scholar
  • 16 Becattini C, Vedovati MC, Ageno W, Dentali F, Agnelli G. Incidence of arterial cardiovascular events after venous thromboembolism: a systematic review and a meta-analysis. J Thromb Haemost 2010; 8 (05) 891-897
    CrossrefPubMedGoogle Scholar
  • 17 Liberman AL, Merkler AE, Gialdini G. et al. Risk of pulmonary embolism after cerebral venous thrombosis. Stroke 2017; 48 (03) 563-567
    CrossrefPubMedGoogle Scholar
  • 18 Schmidt M, Pedersen L, Sørensen HT. The Danish Civil Registration System as a tool in epidemiology. Eur J Epidemiol 2014; 29 (08) 541-549
    CrossrefPubMedGoogle Scholar
  • 19 Schmidt M, Schmidt SA, Sandegaard JL, Ehrenstein V, Pedersen L, Sørensen HT. The Danish National Patient Registry: a review of content, data quality, and research potential. Clin Epidemiol 2015; 7: 449-490
    CrossrefPubMedGoogle Scholar
  • 20 Pottegård A, Schmidt SAJ, Wallach-Kildemoes H, Sørensen HT, Hallas J, Schmidt M. Data Resource Profile: The Danish National Prescription Registry. Int J Epidemiol 2017; 46 (03) 798-798f
    PubMedGoogle Scholar
  • 21 Canhão P, Ferro JM, Lindgren AG, Bousser MG, Stam J, Barinagarrementeria F. ISCVT Investigators. Causes and predictors of death in cerebral venous thrombosis. Stroke 2005; 36 (08) 1720-1725
    CrossrefPubMedGoogle Scholar
  • 22 Saposnik G, Barinagarrementeria F, Brown Jr RD. et al; American Heart Association Stroke Council and the Council on Epidemiology and Prevention. Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011; 42 (04) 1158-1192
    CrossrefPubMedGoogle Scholar
  • 23 Ferro JM, Bousser MG, Canhão P. et al; European Stroke Organization. European Stroke Organization guideline for the diagnosis and treatment of cerebral venous thrombosis - endorsed by the European Academy of Neurology. Eur J Neurol 2017; 24 (10) 1203-1213
    CrossrefPubMedGoogle Scholar
  • 24 Covut F, Kewan T, Perez O, Flores M, Haddad A, Daw H. Apixaban and rivaroxaban in patients with cerebral venous thrombosis. Thromb Res 2019; 173: 77-78
    CrossrefPubMedGoogle Scholar
  • 25 Rao SK, Ibrahim M, Hanni CM. et al. Apixaban for the treatment of cerebral venous thrombosis: a case series. J Neurol Sci 2017; 381: 318-320
    CrossrefPubMedGoogle Scholar
  • 26 Lee GKH, Chen VH, Tan CH. et al. Comparing the efficacy and safety of direct oral anticoagulants with vitamin K antagonist in cerebral venous thrombosis. J Thromb Thrombolysis 2020; 50 (03) 724-731
    CrossrefPubMedGoogle Scholar
  • 27 Lurkin A, Derex L, Fambrini A. et al. Direct oral anticoagulants for the treatment of cerebral venous thrombosis. Cerebrovasc Dis 2019; 48 (1–2): 32-37
    CrossrefPubMedGoogle Scholar
  • 28 Ferro JM, Coutinho JM, Dentali F. et al; RE-SPECT CVT Study Group. Safety and efficacy of dabigatran etexilate vs dose-adjusted warfarin in patients with cerebral venous thrombosis: a randomized clinical trial. JAMA Neurol 2019; 76 (12) 1457-1465
    CrossrefPubMedGoogle Scholar
  • 29 Hsu A, Mistry H, Lala N, Reagan JL. Preliminary findings regarding the use of direct oral anticoagulants in cerebral venous thrombosis. Clin Neurol Neurosurg 2020; 198: 106204
    CrossrefPubMedGoogle Scholar
  • 30 Sundbøll J, Adelborg K, Munch T. et al. Positive predictive value of cardiovascular diagnoses in the Danish National Patient Registry: a validation study. BMJ Open 2016; 6 (11) e012832
    CrossrefPubMedGoogle Scholar
  • 31 Lidegaard Ø, Nielsen LH, Skovlund CW, Skjeldestad FE, Løkkegaard E. Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001-9. BMJ 2011; 343: d6423
    CrossrefPubMedGoogle Scholar