Cyclooxygenase-2 selective nonsteroidal anti-inflammatory drugs and the risk of ischemic stroke: a nested case-control study.
OBJECTIVE
Several randomized trials and a large number of epidemiological studies have provided evidence of an increased risk of acute myocardial infarction associated with the use of cyclooxygenase (COX)-2 selective nonsteroidal anti-inflammatory drugs (NSAIDs). Few data are available concerning the risk of ischemic stroke associated with COX-2 inhibitors.


METHODS
We performed a nested case-control study in a cohort of 469,674 patients registered within the UK General Practice Research Database (GPRD), who had at least 1 prescription of an NSAID between June 1, 2000 and October 31, 2004. A total of 3094 cases with ischemic stroke were identified and 11 859 controls were matched on age, sex, year of cohort entry and general practice. Odds ratios (ORs) of ischemic stroke associated with the use of COX-2 selective NSAIDs were calculated by conditional logistic regression.


RESULTS
Current use of rofecoxib (OR=1.71; 95% CI, 1.33 to 2.18), etoricoxib (OR=2.38; 95% CI, 1.10 to 5.13), but not of celecoxib (OR=1.07; 95% CI, 0.79 to 1.44) was associated with a significantly increased risk of ischemic stroke. For rofecoxib and etoricoxib, ORs tended to increase with higher daily dose and longer duration of use and were also elevated in patients without major stroke risk factors.


CONCLUSIONS
Our study suggests that COX-2 selective NSAIDs differ in their potential to cause ischemic cerebrovascular events. An increased risk of ischemic stroke may be influenced by additional pharmacological properties of individual COX-2 inhibitors.
Andersohn
Frank
F
Department of Clinical Pharmacology, Charité-Universitaetsmedizin Berlin, Berlin, Germany.
Schade
René
R
Suissa
Samy
S
Garbe
Edeltraut
E
D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D002545:Brain Ischemia / Q000453:epidemiology* / Q000209:etiology; D016022:Case-Control Studies; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects*; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D000077613:Etoricoxib; D005260:Female; D006801:Humans; D007783:Lactones / Q000008:administration & dosage / Q000009:adverse effects*; D016015:Logistic Models; D008297:Male; D016347:Medical Records Systems, Computerized; D008875:Middle Aged; D016017:Odds Ratio; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects*; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects*; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects*; D013450:Sulfones / Q000008:administration & dosage / Q000009:adverse effects*; D006113:United Kingdom / Q000453:epidemiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D011720:Pyrazoles; D011725:Pyridines; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; D000068579:Celecoxib; D000077613:Etoricoxib