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DOI: 10.1160/TH15-04-0316
Antithrombotic drugs and subarachnoid haemorrhage risk
A nationwide case-control study in DenmarkPublication 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.
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References
- 1 Schievink WI. Intracranial aneurysms. N Engl J Med 1997; 336: 28-40.
- 2 González-Pérez A, Gaist D, Wallander M-A. et al. Mortality after haemorrhagic stroke: data from general practice (The Health Improvement Network). Neurology 2013; 81: 559-565.
- 3 Vlak MHM, Rinkel GJE, Greebe P. et al. Lifetime risks for aneurysmal subarachnoid haemorrhage: multivariable risk stratification. J Neurol Neurosurg Psychiatry 2013; 84: 619-623.
- 4 Olsen M, Johansen MB, Christensen S. et al. Use of vitamin K antagonists and risk of subarachnoid haemorrhage: a population-based case-control study. Eur J Intern Med 2010; 21: 297-300.
- 5 Schmidt M, Johansen MB, Lash TL. et al. Antiplatelet drugs and risk of subarachnoid haemorrhage: a population-based case-control study. J Thromb Haemost JTH 2010; 8: 1468-1474.
- 6 Risselada R, Straatman H, van Kooten F. et al. Platelet aggregation inhibitors, vitamin K antagonists and risk of subarachnoid haemorrhage. J Thromb Haemost 2011; 9: 517-523.
- 7 Garcia-Rodriguez LA, Gaist D, Morton J. et al. Antithrombotic drugs and risk of haemorrhagic stroke in the general population. Neurology 2013; 81: 566-574.
- 8 Hasan DM, Mahaney KB, Brown RD. et al. Aspirin as a promising agent for decreasing incidence of cerebral aneurysm rupture. Stroke J Cereb Circ 2011; 42: 3156-3162.
- 9 Lynge E, Sandegaard JL, Rebolj M. The Danish National Patient Register. Scand J Public Health 2011; 39: 30-33.
- 10 Gaist D, Vaeth M, Tsiropoulos I. et al. Risk of subarachnoid haemorrhage in first degree relatives of patients with subarachnoid haemorrhage: follow up study based on national registries in Denmark. Br Med J 2000; 320: 141-145.
- 11 Rothman K, Geenland S, Lash T. editors. Modern Epidemiology. 3rd ed. Philadelphia, PA: Wolters Kluwer Health, Lippencott Williams & Wilkins; 2008
- 12 Pedersen CB. The Danish Civil Registration System. Scand J Public Health 2011; 39: 22-25.
- 13 Kildemoes HW, Sørensen HT, Hallas J. The Danish National Prescription Registry. Scand J Public Health 2011; 39: 38-41.
- 14 Ref. program. Referenceprogam for behandling af patienter med apopleksi og TCI (2013) Danish Stroke Society. http://www.dsfa.dk/wpcontent/uploads/REFERENCEPR0GRAMFINAL20131.pdf (in Danish) 2013
- 15 Jensen VM, Rasmussen AW. Danish Education Registers. Scand J Public Health 2011; 39: 91-94.
- 16 Thygesen LC, Daasnes C, Thaulow I. et al. Introduction to Danish (nationwide) registers on health and social issues: structure, access, legislation, and archiving. Scand J Public Health 2011; 39: 12-16.
- 17 Chalouhi N, Ali MS, Jabbour PM. et al. Biology of intracranial aneurysms: role of inflammation. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab 2012; 32: 1659-1676.
- 18 Hasan D, Hashimoto T, Kung D. et al. Upregulation of cyclooxygenase-2 (COX-2) and microsomal prostaglandin E2 synthase-1 (mPGES-1) in wall of ruptured human cerebral aneurysms: preliminary results. Stroke J Cereb Circ 2012; 43: 1964-1967.
- 19 Hasan DM, Chalouhi N, Jabbour P. et al. Evidence that acetylsalicylic acid attenuates inflammation in the walls of human cerebral aneurysms: preliminary results. J Am Heart Assoc 2013; 2: e000019.
- 20 De Rooij NK, Linn FHH, van der Plas JA. et al. Incidence of subarachnoid haemorrhage: a systematic review with emphasis on region, age, gender and time trends. J Neurol Neurosurg Psychiatry 2007; 78: 1365-1372.
- 21 Statens Serum Institut. “Medstat.dk.”. Accessed June 6 2015 http://www.medstat.dk/en.