Antithrombotic drugs and subarachnoid haemorrhage risk A nationwide case-control study in Denmark

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. Lowdose 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.