Nonaspirin Nonsteroidal Anti-Inflammatory Drugs and Risk of Hemorrhagic Stroke: A Systematic Review and Meta-Analysis of Observational Studies

Abstract

Background and purpose: The association between hemorrhagic stroke and use of nonsteroidal anti-inflammatory drugs (NSAIDs) is not well established. We conducted a systematic review and meta-analysis of observation studies to further characterize this possible association.

Methods: Case-control and cohort studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio comparing risk of hemorrhagic stroke among NSAIDs users versus nonusers were systematically searched. Point estimates from each study were extracted. Pooled risk ratios (RR) and 95% confidence intervals (CI) for all NSAIDs and individual NSAIDs were calculated using random-effect, generic inverse variance method.

Results: Ten studies were identified and included in our data analysis. As a single group, NSAIDs use was associated with a small but insignificant risk of hemorrhagic stroke with the pooled RR of 1.09 (95% CI, 0.98-1.22). Individual NSAIDs analysis revealed a significantly increased risk among diclofenac and meloxicam users (RR 1.27; 95% CI, 1.02-1.59 and RR 1.27; 95% CI, 1.08-1.50, respectively). The risk estimate for rofecoxib users was higher, but statistically nonsignificant (RR 1.35; 95% CI, 0.88-2.06).

Conclusions: Overall, the use of NSAIDs is not associated with an increased risk of hemorrhagic stroke, although this risk was modestly significantly elevated in diclofenac and meloxicam users.

Keywords: cyclooxygenase; hemorrhagic stroke; meta-analysis; nonsteroidal anti-inflammatory drugs; stroke.