Non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease: an observational cohort study

Lancet. 2002 Jan 12;359(9301):118-23. doi: 10.1016/S0140-6736(02)07370-1.


Background: Non-aspirin, non-steroidal anti-inflammatory drugs (NANSAIDs) have complex effects that could either prevent or promote coronary heart disease. Comparison of the NANSAID rofexocib with naproxen showed a substantial difference in acute myocardial infarction risk, which has been interpreted as a protective effect of naproxen. We did an observational study to measure the effects of NANSAIDs, including naproxen, on risk of serious coronary heart disease.

Methods: We used data from the Tennessee Medicaid programme obtained between Jan 1, 1987, and Dec 31, 1998, to identify a cohort of new NANSAID users (n=181 441) and an equal number of non-users, matched for age, sex, and date NANSAID use began. Both groups were 50-84 years of age, were not resident in a nursing home, and did not have life-threatening illness. The study endpoint was hospital admission for acute myocardial infarction or death from coronary heart disease.

Findings: During 532634 person-years of follow-up, 6362 cases of serious coronary heart disease occurred, or 11.9 per 1000 person-years. Multivariate-adjusted rate ratios for current and former use of NANSAIDs were 1.05 (95% CI 0.97-1.14) and 1.02 (0.97-1.08), respectively. Rate ratios for naproxen, ibuprofen, and other NANSAIDs were 0.95 (0.82-1.09), 1.15 (1.02-1.28), and 1.03 (0.92-1.16), respectively. There was no protection among long-term NANSAID users with uninterrupted use; the rate ratio among current users with more than 60 days of continuous use was 1.05 (0.91-1.21). When naproxen was directly compared with ibuprofen, the current-use rate ratio was 0.83 (0.69-0.98).

Interpretation: Absence of a protective effect of naproxen or other NANSAIDs on risk of coronary heart disease suggests that these drugs should not be used for cardioprotection.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age Distribution
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Aspirin / pharmacology
  • Aspirin / therapeutic use
  • Bias
  • Cause of Death
  • Cohort Studies
  • Coronary Disease / epidemiology*
  • Coronary Disease / etiology
  • Coronary Disease / prevention & control*
  • Death Certificates
  • Drug Prescriptions / statistics & numerical data
  • Female
  • Humans
  • Ibuprofen / pharmacology
  • Ibuprofen / therapeutic use*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Myocardial Infarction / epidemiology*
  • Myocardial Infarction / etiology
  • Myocardial Infarction / prevention & control*
  • Naproxen / pharmacology
  • Naproxen / therapeutic use*
  • Patient Admission / statistics & numerical data
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Aggregation Inhibitors / therapeutic use
  • Registries
  • Regression Analysis
  • Risk Factors
  • Tennessee / epidemiology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Platelet Aggregation Inhibitors
  • Naproxen
  • Aspirin
  • Ibuprofen