On behalf of the Investigators of The Safety of Nonsteroidal Anti-inflammatory Drugs (SOS) project http://www.sos-nsaids-project.org/
Stroke risk and NSAIDs: a systematic review of observational studies†
Article first published online: 3 OCT 2011
Copyright © 2011 John Wiley & Sons, Ltd.
Pharmacoepidemiology and Drug Safety
Volume 20, Issue 12, pages 1225–1236, December 2011
How to Cite
Varas-Lorenzo, C., Riera-Guardia, N., Calingaert, B., Castellsague, J., Pariente, A., Scotti, L., Sturkenboom, M. and Perez-Gutthann, S. (2011), Stroke risk and NSAIDs: a systematic review of observational studies. Pharmacoepidem. Drug Safe., 20: 1225–1236. doi: 10.1002/pds.2227
NRG and CVL abstracted and compiled the data, BC performed the analyses, and CVL drafted the manuscript. CVL, NRG, BC, JC, AP, LS, MS, and SPG facilitated the interpretation of the findings. CVL, NRG, JC, AP, LS, MS, and SPG oversaw the design of the study and helped to draft the manuscript. All coauthors participated in the writing of the manuscript and approved the version submitted for publication.
- Issue published online: 22 NOV 2011
- Article first published online: 3 OCT 2011
- Manuscript Accepted: 12 JUL 2011
- Manuscript Revised: 13 MAY 2011
- Manuscript Received: 25 FEB 2011
- European Community's Seventh Framework Programme. Grant Number: 223495
- observational studies;
- anti-inflammatory agents;
To perform a quantitative systematic review of observational studies on the risk of stroke associated with the use of individual NSAIDs.
Methods and results
Searches were conducted using the Medline database within PubMed (1990–2008). Observational cohort or case–control studies were eligible if reported on the risk of cardiovascular events associated with individual NSAIDs versus the nonuse of NSAIDs. We found 3193 articles, in which 75 were eligible for review and abstraction. Of the 75 articles, 6 reported relative risk (RR) of stroke. Data were abstracted into a database using a standardized entry form. Two authors assessed study quality, and discrepancies were resolved by consensus.
The pooled RR of all subtypes of incident stroke was increased with the current use of rofecoxib (RR = 1.64, 95% CI = 1.15–2.33) and diclofenac (RR = 1.27, 95% CI = 1.08–1.48). The pooled estimates for naproxen, ibuprofen, and celecoxib were close to unity. The risk of ischemic stroke was also increased with rofecoxib (RR = 1.82, 95% CI = 1.09–3.04) and diclofenac (RR = 1.20, 95% CI = 0.99–1.45). Data were inadequate to estimate the pooled RR by dose and duration, for other individual NSAIDs or nonischemic stroke subtypes.
This meta-analysis supports an increased risk of ischemic stroke with the current use of rofecoxib and diclofenac. Additional studies are required to evaluate most individual NSAIDS, the effect of dose and duration, and the subtypes of stroke. Copyright © 2011 John Wiley & Sons, Ltd.