Nonsteroidal antiinflammatory drugs and acute myocardial infarction in patients with no major risk factors.

Objective: To assess the risk of long-term use of five nonsteroidal antiinflammatory drugs (NSAIDs)--rofecoxib, celecoxib, ibuprofen, naproxen, and diclofenac--in relation to acute myocardial infarction.

Methods: Five separate nested case-control studies, one for each NSAID, designed to minimize important biases present in other observational studies. Setting. University-affiliated research program. Data Source. The United Kingdom General Practice Research Database (GPRD).

Results: We identified all people in the GPRD aged 30-79 years who had a first recorded prescription for rofecoxib, celecoxib, ibuprofen, naproxen, or diclofenac after January 1, 1999. Cases of newly diagnosed, first-time acute myocardial infarction were then identified from the study population, along with matched control subjects. Relative risk estimates for acute myocardial infarction in patients with no recorded major clinical risk factors for acute myocardial infarction were determined for each NSAID according to receipt of 2-4, 5-9, 10-19, or 20 or more prescriptions compared with receipt of only 1 prescription. Results were adjusted for relevant variables possibly related to the risk for acute myocardial infarction. No material elevation of risk according to the number of prescriptions received for ibuprofen or naproxen was noted. However, a substantial increased risk similar to that found in clinical trials was noted in patients who received 10 or more prescriptions for rofecoxib, celecoxib, or diclofenac.

Conclusions: Extensive use of rofecoxib, celecoxib, and diclofenac increases the risk of acute myocardial infarction, but similar use of ibuprofen and naproxen does not.