Role of dose potency in the prediction of risk of myocardial infarction associated with nonsteroidal anti-inflammatory drugs in the general population

J Am Coll Cardiol. 2008 Nov 11;52(20):1628-36. doi: 10.1016/j.jacc.2008.08.041.


Objectives: We studied the association between the frequency, dose, and duration of different nonsteroidal anti-inflammatory drugs (NSAIDs) and the risk of myocardial infarction (MI) in the general population. We verified whether the degree of inhibition of whole blood cyclooxygenase (COX)-2 by average circulating drug levels can be a surrogate biochemical predictor of the risk of MI by NSAIDs.

Background: There is evidence that both traditional NSAIDs and selective inhibitors of COX-2 may increase the risk of MI.

Methods: From the THIN (The Health Improvement Network) database, we identified 8,852 cases of nonfatal MI in patients 50 to 84 years old between 2000 and 2005 and conducted a nested case-control analysis. We correlated the risk of MI with the degree of inhibition of platelet COX-1 and monocyte COX-2 in vitro by average therapeutic concentrations of individual NSAIDs.

Results: The risk of MI was increased with current use of NSAIDs (relative risk [RR]: 1.35; 95% confidence interval [CI]: 1.23 to 1.48). The risk increased with treatment duration and daily dose. We found a significant correlation between the degree of inhibition in vitro of whole blood COX-2 (r(2) = 0.7458, p = 0.0027), but not whole blood COX-1 (r(2) = 0.0007, p = 0.947), and the risk of MI associated with individual NSAIDs that lacked complete suppression (> or =95%) of platelet COX-1 activity. Individual NSAIDs with a degree of COX-2 inhibition <90% at therapeutic concentrations presented an RR of 1.18 (95% CI: 1.02 to 1.38), whereas those with a greater COX-2 inhibition had an RR of 1.60 (95% CI: 1.41 to 1.81).

Conclusions: Our findings suggest that the variable risk of MI among NSAIDs that do not inhibit platelet COX-1 completely and persistently is largely related to their extent of COX-2 inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Epoprostenol / antagonists & inhibitors
  • Humans
  • Middle Aged
  • Myocardial Infarction / chemically induced*
  • Retrospective Studies
  • Risk Assessment


  • Anti-Inflammatory Agents, Non-Steroidal
  • Epoprostenol