title: Antithrombotic drugs and subarachnoid haemorrhage risk. A nationwide case-control study in Denmark.
abstract: 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.
authors.forename: Anton
authors.initials: A
authors.lastname: Pottegård
authors.forename: Luis Alberto
authors.initials: LA
authors.lastname: García Rodríguez
authors.forename: Frantz Rom
authors.initials: FR
authors.lastname: Poulsen
authors.forename: Jesper
authors.initials: J
authors.lastname: Hallas
authors.affiliation: David Gaist, professor, consultant, Dept. Neurology, Odense University Hospital &, Institute of Clinical Medicine, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark, E-mail: dgaist@health.sdu.dk.
authors.forename: David
authors.initials: D
authors.lastname: Gaist
mesh_terms: D000368:Aged; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D016022:Case-Control Studies; D000077144:Clopidogrel; D003718:Denmark; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019635:Neurosurgical Procedures; D011183:Postoperative Complications / Q000517:prevention & control*; D012306:Risk; D013345:Subarachnoid Hemorrhage / Q000453:epidemiology* / Q000209:etiology; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control*; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014812:Vitamin K / Q000037:antagonists & inhibitors
chemical_list: D005343:Fibrinolytic Agents; D014812:Vitamin K; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
keywords: Anticoagulants; aspirin; clopidogrel; platelet aggregation inhibitors; subarachnoid haemorrhage