Risk of acute myocardial infarction during use of individual NSAIDs: A nested case-control study from the SOS project

PLoS One. 2018 Nov 1;13(11):e0204746. doi: 10.1371/journal.pone.0204746. eCollection 2018.

Abstract

Background: Use of selective COX-2 non-steroidal anti-inflammatory drugs (NSAIDs) (coxibs) has been associated with an increased risk of acute myocardial infarction (AMI). However, the risk of AMI has only been studied for very few NSAIDs that are frequently used.

Objectives: To estimate the risk of AMI for individual NSAIDs.

Methods: A nested case-control study was performed from a cohort of new NSAID users ≥18 years (1999-2011) matching cases to a maximum of 100 controls on database, sex, age, and calendar time. Data were retrieved from six healthcare databases. Adjusted odds ratios (ORs) of current use of individual NSAIDs compared to past use were estimated per database. Pooling was done by two-stage pooling using a random effects model (ORmeta) and by one-stage pooling (ORpool).

Results: Among 8.5 million new NSAID users, 79,553 AMI cases were identified. The risk was elevated for current use of ketorolac (ORmeta 2.06;95%CI 1.83-2.32, ORpool 1.80; 1.49-2.18) followed, in descending order of point estimate, by indometacin, etoricoxib, rofecoxib, diclofenac, fixed combination of diclofenac with misoprostol, piroxicam, ibuprofen, naproxen, celecoxib, meloxicam, nimesulide and ketoprofen (ORmeta 1.12; 1.03-1.22, ORpool 1.00;0.86-1.16). Higher doses showed higher risk estimates than lower doses.

Conclusions: The relative risk estimates of AMI differed slightly between 28 individual NSAIDs. The relative risk was highest for ketorolac and was correlated with COX-2 potency, but not restricted to coxibs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Case-Control Studies
  • Diclofenac / adverse effects
  • Etoricoxib / adverse effects
  • Female
  • Humans
  • Indomethacin / adverse effects
  • Ketorolac / adverse effects
  • Lactones / adverse effects
  • Male
  • Middle Aged
  • Myocardial Infarction / chemically induced*
  • Odds Ratio
  • Risk Factors
  • Sulfones / adverse effects

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Lactones
  • Sulfones
  • rofecoxib
  • Diclofenac
  • Etoricoxib
  • Indomethacin
  • Ketorolac

Grants and funding

The research leading to the results of this study has received funding from the European Community’s Seventh Framework Programme under grant agreement number 223495 - the SOS project. The funding agency had no role in the design and conduct of the study; nor in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript.