Risk of Stroke Associated With Nonsteroidal Anti-Inflammatory Drugs: A Nested Case-Control Study

Abstract

Background and Purpose— Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with bleeding complications and may affect the risk of hemorrhagic stroke through inhibition of platelet cyclooxygenase-1. We performed a population-based case-control study to estimate the risk of intracerebral hemorrhage, subarachnoid hemorrhage, and ischemic stroke in users of NSAIDs. Methods— We used a population-based patient registry to identify all patients with a first-ever stroke discharge diagnosis in the period of 1994 to 1999. All diagnoses were validated according to predefined criteria. We selected 40 000 random controls from the background population. Information on drug use for cases and controls was retrieved from a prescription registry. Odds ratios were adjusted for age, sex, calendar year, and use of other medication. To evaluate the effect of various potential confounders not recorded in the register, we performed separate analyses on data from 2 large population-based surveys with more detailed information on risk factors. Results— The cases were classified as intracerebral hemorrhage (n=659), subarachnoid hemorrhage (n=208), and ischemic stroke (n=2717). The adjusted odds ratio of stroke in current NSAID users compared with never users was 1.2 (95% CI, 0.9 to 1.6) for intracerebral hemorrhage, 1.2 (95% CI, 0.7 to 2.1) for subarachnoid hemorrhage and 1.2 (95% confidence interval, 1.0 to 1.4) for ischemic stroke. The survey data indicated that additional confounder control would not have led to an increase in relative risk estimates. Conclusions— Current exposure to NSAIDs is not a risk factor for intracerebral hemorrhage or subarachnoid hemorrhage. Furthermore, NSAIDs probably offer no protection against first-ever ischemic stroke.