The balance between severe cardiovascular and gastrointestinal events among users of selective and non-selective non-steroidal anti-inflammatory drugs

Abstract

Objective: To simultaneously assess cardiovascular (CV) and gastrointestinal (GI) risk with traditional non-steroidal anti-inflammatory drugs (tNSAIDs) and cyclo-oxygenase 2 (COX-2) inhibitors.

Methods: Using the PHARMO Record Linkage System, including drug-dispensing and hospitalisation data of >2 million residents of The Netherlands, subjects with first hospitalisation for acute myocardial infarction (AMI), CV and GI events were identified. Use of COX-2 inhibitors and traditional non-selective NSAIDs was classified into remote, recent and current. Cases were matched to controls in a 1:4 ratio on age and event date. Multivariate analyses adjusted for gender, history of hospitalisations and medications.

Results: Compared to remote use, AMI risk was increased among current users of COX-2 inhibitors combined (adjusted odds ratio (OR) 1.73, 95% CI 1.37 to 2.19) and tNSAIDs combined (OR 1.41, 95% CI 1.23 to 1.61). AMI risk with celecoxib (OR 2.53, 95% CI 1.53 to 4.18), rofecoxib (OR 1.60, 95% CI 1.22 to 2.10), ibuprofen (OR 1.56, 95% CI 1.19 to 2.05) and diclofenac (OR 1.51, 95% CI 1.22 to 1.87) was significantly increased. CV risk with current use of individual COX-2 inhibitors and tNSAIDs was significantly increased (OR from 1.17 to 1.64), as was GI risk with current use of rofecoxib (OR 1.99, 95% CI 1.51 to 2.63), naproxen (OR 4.44, 95% CI 3.36 to 5.86), ibuprofen (OR 1.90, 95% CI 1.40 to 2.58), diclofenac (OR 4.77, 95% CI 3.94 to 5.76), other tNSAIDs (OR 2.59, 95% CI 2.08 to 3.21), but not celecoxib (OR 1.36, 95% CI 0.70 to 2.66). Compared to current use of celecoxib and AMI risk was significantly decreased with current use of naproxen (OR 0.48, 95% CI 0.26 to 0.87) only. GI risk was increased with current naproxen (OR 3.26, 95% CI 1.59 to 6.70) and diclofenac (OR 3.50, 95% CI 1.76 to 6.98).

Conclusions: AMI and CV risk increased similarly with individual COX-2 inhibitors and tNSAIDs, whereas GI risk was found to be greater with naproxen and diclofenac. Residual confounding and "channelling" cannot be excluded.