Cyclooxygenase selectivity of nonsteroidal anti-inflammatory drugs and risk of stroke.
BACKGROUND
In clinical trials, cyclooxygenase (COX)-2-selective nonsteroidal anti-inflammatory drugs (NSAIDs) were associated with an increased risk of thromboembolic events. We studied the association between NSAID use and risk of stroke in the prospective, population-based Rotterdam Study.


METHODS
We followed 7636 persons free of stroke at baseline (1991-1993) for incident stroke until September 2004. Data on all filled prescriptions came from pharmacy records. With Cox regression models, we calculated crude and adjusted hazard ratios (HRs) of stroke for time-dependent current use, compared with never use, of NSAIDs grouped according to COX selectivity (COX-1 selective, nonselective, and COX-2 selective) and individual NSAIDs.


RESULTS
At baseline, the mean age of the study sample was 70.2 years, and 61.3% were female. During 70 063 person-years of follow-up (mean, 9.2 years), 807 persons developed a stroke (460 ischemic, 74 hemorrhagic, and 273 unspecified). Current users of nonselective (HR, 1.72; 95% confidence interval [CI], 1.22-2.44) and COX-2-selective (HR, 2.75; 95% CI, 1.28-5.95) NSAIDs had a greater risk of stroke, but not users of COX-1-selective NSAIDs (HR, 1.10; 95% CI, 0.41-2.97). Hazard ratios (95% CIs) for ischemic stroke were 1.68 (1.05-2.69) for nonselective and 4.54 (2.06-9.98) for COX-2-selective NSAIDs. For individual NSAIDs, current use of the nonselective naproxen (HR, 2.63; 95% CI, 1.47-4.72) and the COX-2-selective rofecoxib (HR, 3.38; 95% CI, 1.48-7.74) was associated with a greater risk of stroke. Hazard ratios (95% CIs) for diclofenac (1.60 [1.00-2.57]), ibuprofen (1.47 [0.73-3.00]), and celecoxib (3.79 [0.52-27.6]) were greater than 1.00 but were not statistically significant.


CONCLUSIONS
In the general population, we found a greater risk of stroke with current use of nonselective and COX-2-selective NSAIDs. The risk of stroke was not limited to the use of COX-2-selective NSAIDs.
Haag
Mendel D M
MD
Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, the Netherlands.
Bos
Michiel J
MJ
Hofman
Albert
A
Koudstaal
Peter J
PJ
Breteler
Monique M B
MM
Stricker
Bruno H C
BH
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000139:chemically induced* / Q000453:epidemiology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors