Antiplatelet drugs and risk of subarachnoid hemorrhage: a population-based case-control study

Background: Antiplatelet drug use increases bleeding risk, but its role in precipitating subarachnoid hemorrhage remains unclear. Objectives: We examined whether the use of low-dose acetylsalicylic acid (LDA), clopidogrel or dipyridamole increased the risk of subarachnoid hemorrhage. Patients/Methods: This population-based case-control study was conducted in northern Denmark. We used the Danish National Patient Registry to identify all persons admitted to neurosurgery or neurology departments with a first diagnosis of subarachnoid hemorrhage between 1997 and 2008 (n = 1186). Using risk-set sampling, we selected 10 population controls (n = 11 840) for each case, matched by age and sex. We obtained data on prescriptions for antiplatelet drugs, use of other medications and comorbidity from medical databases. We used conditional logistic regression to compute odds ratios with 95% confidence intervals (CIs), controlling for confounding factors. Results: One hundred and nine cases (9.2%) and 910 controls (7.7%) used antiplatelet drugs. Among cases, 104 (8.8%) used LDA and 11 (0.9%) used dipyridamole. Among controls, 891 (7.5%) used LDA and 48 (0.4%) used dipyridamole. As compared with not using any antiplatelet drugs during the study period, the adjusted odds ratios were 1.03 (95% CI 0.81-1.32) for long-term LDA use, 2.52 (95% CI 1.37-4.62) for new LDA use, and 2.09 (95% CI 1.04-4.23) for long-term dipyridamole use. Owing to the low number of users, data were inconclusive for clopidogrel. Conclusions: Long-term dipyridamole use and new LDA use were associated with an increased risk of subarachnoid hemorrhage. Because of the limited precision of these risk estimates, however, caution is advised in their interpretation. Long-term LDA use was not associated with subarachnoid hemorrhage.