BMJ 1999;318:759-764 ( 20 March )

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Risk of primary intracerebral haemorrhage associated with aspirin and non-steroidal anti-inflammatory drugs: case-control study

Amanda G Thrift, research fellow, ^a John J McNeil, head of department, ^a Andrew Forbes, head of biostatics unit, ^a Geoffrey A Donnan, head of department. ^b

^a Department of Epidemiology and Preventive Medicine, Monash Medical School, Alfred Hospital, Prahran 3181, Australia, ^b Neurology Department, Austin and Repatriation Hospitals, Heidelberg, Victoria 3084, Australia

Correspondence to: Dr A Thrift, National Stroke Research Institute, Austin and Repatriation Medical Centre, West Heidelberg, Victoria 3081, Australia thrift{at}austin.unimelb.edu.au

Objective: To examine the association between use of aspirin or other non-steroidal anti-inflammatory drugs and intracerebral haemorrhage.
Design: Case-control study.
Setting: 13 major city hospitals in the Melbourne and metropolitan area.
Subjects: 331 consecutive cases of stroke verified by computed tomography or postmortem examination, and 331 age (± 5 years) and sex matched controls who were community based neighbours.
Interventions: Questionnaire administered to all subjects either directly or by proxy with the next of kin. Drug use was validated by reviewing prescribing records held by the participants' doctors.
Main outcome measures: Previous use of aspirin or other non-steroidal anti-inflammatory drugs.
Results: Univariate analysis showed no increased risk of intracerebral haemorrhage with low dose aspirin use in the preceding 2 weeks. Using multiple logistic regression to control for possible confounding factors, the odds ratio associated with the use of aspirin was 1.00 (95% confidence interval 0.60 to 1.66, P=0.998) and the odds ratio associated with the use of other non-steroidal anti-inflammatory drugs was 0.85 (0.45 to 1.61, P=0.611) compared with respective non-users in the preceding fortnight. Moderate to high doses of aspirin (>1225 mg/week spread over at least three doses) yielded an odds ratio of 3.05 (1.02 to 9.14, P=0.047). There was no evidence of an increased risk among subgroups defined by age, sex, blood pressure status, alcohol intake, smoking, and the presence or absence of previous cardiovascular disease.
Conclusions: No increase in risk of intracerebral haemorrhage was found among aspirin users overall or among those who took low doses of the drug or other non-steroidal anti-inflammatory drugs. These data provide evidence that doses of aspirin usually used for prophylaxis against vascular disease produce no substantial increase in risk of intracerebral haemorrhage.

Key messages Low to moderate dose aspirin treatment does not substantially increase the risk of intracerebral haemorrhage No increase in risk of intracerebral haemorrhage was observed among users of non-steroidal anti-inflammatory drugs Users of high doses of aspirin may have an increased risk of intracerebral haemorrhage, but numbers of cases in the group were small and the finding is therefore tentative

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Aspirin use does not contribute to intracerebral haemorrhage
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