Thromb Haemost 2015; 114(05): 1064-1075
DOI: 10.1160/TH15-04-0316
Stroke, Systemic or Venous Thromboembolism
Schattauer GmbH

Antithrombotic drugs and subarachnoid haemorrhage risk

A nationwide case-control study in Denmark
Anton Pottegård
1   Clinical Pharmacology, Department of Public Health, University of Southern Denmark
,
Luis Alberto García Rodríguez
2   El Centro Español Investigatión Farmacoepidemiológica (CEIFE), Madrid, Spain
,
Frantz Rom Poulsen
3   Department of Neurosurgery, Odense University Hospital, Odense, Denmark
,
Jesper Hallas
1   Clinical Pharmacology, Department of Public Health, University of Southern Denmark
,
David Gaist
4   Department of Neurology, Odense University Hospital & Institute of Clinical Medicine, University of Southern Denmark, Odense, Denmark
› Author Affiliations
Further Information

Publication History

Received: 16 April 2015

Accepted after major revision: 13 June 2015

Publication Date:
06 December 2017 (online)

Summary

The study objective was to investigate the relationship between use of antithrombotic drugs and subarachnoid haemorrhage (SAH). We identified patients discharged from Danish neurosurgery units with a first-ever SAH diagnosis in 2000 to 2012 (n=5,834). For each case, we selected 40 age-, sex- and period-matched population controls. Conditional logistic regression models were used to estimate odds ratios (aOR), adjusted for comorbidity, education level, and income. Low-dose aspirin (ASA) use for < 1 month was associated with an increased risk of SAH (aOR 1.75, 95% confidence interval [CI] 1.28–2.40). This aOR decreased to 1.26 (95%CI: 0.98–1.63) with 2–3 months of ASA use, and approached unity with use for more than three months (1.11, 95%CI 0.97–1.27). Analyses with first-time users confirmed this pattern, which was also observed for clopidogrel. ASA treatment for three or more years was associated with an aOR of SAH of 1.13 (95%CI: 0.86–1.49). Short-term use (< 1 month) of vitamin K-antagonists (VKA) yielded an aOR of 1.85 (95%CI 0.97–3.51) which dropped after 3+ years to 1.24, 95%CI: 0.86–1.77. The risk of SAH was higher in subjects in dual antithrombotic treatment (aOR 2.08, 95%CI: 1.26–3.44), and in triple antithrombotic treatment (aOR 5.74, 95%CI: 1.76–18.77). In conclusion, use of aspirin,clopidogrel and VKA were only associated with an increased risk of SAH in the first three months after starting treatment. Long-term aspirin use carried no reduced SAH risk. Results should be interpreted cautiously due to their observational nature.