NSAID use in patients with prior MI

A new study points out the risk of nonsteroidal anti-inflammatory drug (NSAID) use in patients who have had a myocardial infarction (MI) — suggesting that even brief use increases the risk for death and recurrent MI. Researchers from Denmark reviewed the records of nearly 84,000 patients who were admitted with first time MI and their subsequent NSAID use. The risk of death and recurrent MI was correlated to the duration of NSAID treatment. From 1997-2006, 42.3% of patients received NSAIDs. There were more than 35,000 deaths or recurrent MIs in the cohort of whom 43% had filled a prescription for an NSAID. Use of an NSAID was significantly associated with an increased risk of death or recurrent MI at the beginning of treatment (hazard ratio [HR] 1.45; 95% confidence interval [CI], 1.29 to 1.62) and persisted throughout the NSAID treatment course (HR 1.55; 95% CI, 1.46 to 1.64 after 90 days), returning to baseline soon after stopping the drug. The risk of death or recurrent MI varied with different drugs and was somewhat higher with increased COX-2 selectivity. Diclofenac was associated with the highest risk (HR 3.26; 95% CI, 2.57 to 3.86). Duration of therapy was also reviewed with diclofenac causing an increased risk from the beginning of treatment and persisting throughout the treatment course. Ibuprofen showed an increased risk when used for more than one week, whereas celecoxib showed an increased risk after 14-30 days of treatment. Naproxen was not associated with a statistically significant increased risk of death or MI for the entire treatment duration. The authors conclude that short-term treatment with most NSAIDs is associated with increased cardiovascular risk. This suggests that there is no apparent safe therapeutic window for NSAIDs in patients with prior MI and "challenge the current recommendations of low-dose and short-term use of NSAIDs as being safe" (Circulation 2011;123:2226-2235). One interesting aspect of this study was the use of rofecoxib (Vioxx) prior to its withdrawal in 2004. While rofecoxib was found to increase cardiovascular risk (the reason for its withdrawal from the market), it appeared to be no more dangerous than other commonly used NSAIDs and was apparently safer than diclofenac.