Ischemic stroke risk not alike for all COX-2 inhibitors: study
Last Updated: 2006-07-07 18:47:41 -0400 (Reuters Health)
By Megan Rauscher
NEW YORK (Reuters Health) - Cyclooxygenase-2 (COX-2) selective nonsteroidal anti-inflammatory drugs (NSAIDs) differ with respect to their cerebrovascular safety, a study shows. Celecoxib is not associated with an increased risk of ischemic stroke whereas rofecoxib and etoricoxib do appear to increase the risk, investigators report in the July issue of Stroke.
"Mechanisms beyond COX-2 selectivity, e.g. the degree of causing hypertension or fluid retention, may influence the risk associated with each individual NSAID," noted senior investigator Dr. Frank Andersohn from the Institute of Clinical Pharmacology, Humboldt-University Berlin in comments to Reuters Health.
While several studies have shown an increased risk of acute myocardial infarction with the use of COX-2 inhibitors, few have looked at the risk of ischemic stroke.
Dr. Andersohn's team analyzed data contained in the UK General Practice Research Database on 469,674 patients prescribed at least one NSAID during a 4-year period. They identified 3,094 case patients with ischemic stroke and matched them to 11,859 controls.
The odds ratio of ischemic stroke was significantly elevated with current use of rofecoxib (OR = 1.71) or etoricoxib (OR = 2.38), but not with celecoxib (OR = 1.07), the investigators report.
"Among the non-selective NSAIDs, diclofenac, but not ibuprofen or naproxen, was also associated with a slightly increased risk of ischemic stroke," Dr. Andersohn said.
The ischemic stroke risk associated with rofecoxib and etoricoxib tended to increase with higher daily dose and longer duration of use. "Even in patients without cerebrovascular disease, atrial fibrillation and hypertension, risk estimates for rofecoxib and etoricoxib were elevated," the authors point out.
This study, Dr. Andersohn said, shows that "the potential of COX-2 selective NSAIDs to increase the risk of ischemic stroke may not be alike. From the COX-2 inhibitors under investigation, celecoxib seemed to be safer with respect to the outcome."
The findings for rofecoxib in this study mirror those of a placebo-controlled trial, which showed a 2-fold risk of ischemic stroke with rofecoxib versus placebo, the team notes. However, in another trial, an increased risk of ischemic stroke was not observed for rofecoxib versus naproxen.
The finding of no increased risk of ischemic stroke for celecoxib is in agreement with the Adenoma Prevention with Celecoxib (APC) trial, the researchers say, in which the percentage of nonfatal stroke was the same for celecoxib 400 mg/d and placebo (both 0.4%).
The finding of an increased risk of ischemic stroke with etoricoxib needs to be interpreted with caution, Dr. Andersohn and colleagues emphasize, given that it is based on small numbers of exposed patients.
Stroke 2006;37:1725-1730.
