Antirheumatic drug use and the risk of acute myocardial infarction

Arthritis Rheum. 2006 Aug 15;55(4):531-6. doi: 10.1002/art.22094.


Objective: To assess the risk of acute myocardial infarction (AMI) associated with the use of disease-modifying antirheumatic drugs (DMARDs) and other medications commonly used in rheumatoid arthritis (RA).

Methods: We conducted a nested case-control analysis within a cohort of subjects with RA, observed between 1999 and 2003, identified from the PharMetrics claims database. For each first AMI hospitalization identified during followup, 10 controls matched on sex, age, and time of study entry were randomly selected from the cohort. Conditional logistic regression was used to estimate the rate ratio (RR) of AMI associated with the current use of anti-RA therapy, as measured from dispensed prescriptions, after adjustment for AMI risk factors.

Results: The cohort included 107,908 subjects (average age 54 years at cohort entry). During followup, 558 AMI cases occurred (3.4 per 1,000 per year). AMI rate was significantly decreased with the current use of any DMARD (adjusted RR 0.80, 95% confidence interval [95% CI] 0.65-0.98). This effect was consistent across all DMARDs, including methotrexate (RR 0.81, 95% CI 0.60-1.08), leflunomide (RR 0.28, 95% CI 0.12-0.65), and other traditional DMARDs (RR 0.67, 95% CI 0.46-0.97), but not biologic agents (RR 1.30, 95% CI 0.92-1.83). AMI rate increased with the use of glucocorticoids (RR 1.32, 95% CI 1.02-1.72) but not with nonselective nonsteroidal antiinflammatory drugs (RR 1.05, 95% CI 0.81-1.36) or cyclooxygenase 2 (COX-2) inhibitors (RR 1.11, 95% CI 0.87-1.43).

Conclusion: DMARD use is associated with a reduction in AMI risk in patients with RA. No risk increase was found with the COX-2 inhibitors in this population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Humans
  • Isoxazoles / therapeutic use
  • Leflunomide
  • Male
  • Methotrexate / therapeutic use
  • Middle Aged
  • Myocardial Infarction / epidemiology*
  • Myocardial Infarction / prevention & control*
  • Random Allocation
  • Treatment Outcome


  • Antirheumatic Agents
  • Isoxazoles
  • Leflunomide
  • Methotrexate