Objective: To simultaneously assess cardiovascular (CV) and gastrointestinal (GI) risk with tNSAIDs and coxibs.
Methods: Using the PHARMO Record Linkage System, including drug-dispensing and hospitalization data of >2 million residents of the Netherlands, subjects with first hospitalization for Acute Myocardial Infarction (AMI), CV and GI events were identified. Use of COX-2-inhibitors (coxibs) and traditional non-selective NSAIDs (tNSAIDs) was classified into remote, recent and current. Cases were matched to controls in a 1 to 4 ratio on age and event date. Multivariate analyses adjusted for gender, history of hospitalizations and medications.
Results: Compared to remote use, AMI risk was increased among current users of coxibs combined (adjusted OR 1.73, 95% confidence interval 1.37-2.19) and tNSAIDs combined (1.41, 1.23-1.61). AMI risk with celecoxib (2.53, 1.53 4.18), rofecoxib (1.60, 1.22-2.10), ibuprofen (1.21, 1.19-2.05) and diclofenac (1.51, 1.22-1.87) was significantly increased. CV Risk with current use of individual coxibs and tNSAIDs was significantly increased (OR from 1.17 to 1.64), as was GI risk with current use of rofecoxib (1.99, 1.51-2.63), naproxen (4.44, 3.36-5.86), ibuprofen (1.90, 1.40-2.58), diclofenac (4.77, 3.94-5.76), other tNSAIDs (2.59, 2.08-3.21), but not celecoxib (1.36, 0.70-2.66). Compared to current use of celecoxib, AMI and CV risk was significantly decreased with current use of naproxen (0.48, 0.26-0.87) only. GI risk was increased with current naproxen (3.26, 1.59-6.70) and diclofenac (3.50, 1.76-6.98).
Conclusions: AMI and CV risk was similarly increased with individual coxibs and tNSAIDs whereas GI risk was found greater with naproxen and diclofenac. Residual confounding and “channelling” can not be excluded.