Does tumor necrosis factor alpha inhibition promote or prevent heart failure in patients with rheumatoid arthritis?

Arthritis Rheum. 2008 Mar;58(3):667-77. doi: 10.1002/art.23281.


Objective: To determine the hazard risk of developing or worsening heart failure in rheumatoid arthritis (RA) patients treated with tumor necrosis factor alpha (TNFalpha) inhibitors.

Methods: RA patients ages 18-75 years who started treatment with infliximab, etanercept, or adalimumab (n = 2,757), or conventional disease-modifying antirheumatic drugs (controls; n = 1,491) at the time of enrollment in a German biologics register were studied. Cox proportional hazards models were applied to investigate the influence of disease-related and treatment-specific risk factors on the incidence or worsening of heart failure.

Results: The 3-year incidence rates of heart failure in patients with and patients without cardiovascular disease at the start of treatment were 2.2% and 0.4%, respectively. After adjustment for traditional cardiovascular risk factors, an increased risk of developing heart failure was found in patients who had a higher 28-joint Disease Activity Score at followup (hazard ratio [HR] 1.47 [95% confidence interval 1.07-2.02], P = 0.019). A residual nonsignificant risk related to treatment with TNFalpha inhibitors remained (adjusted HR 1.66 [95% confidence interval 0.67-4.1], P = 0.28). This residual risk was balanced by the efficacy of the anti-TNF treatment. When only baseline characteristics were taken into account, the HR related to TNFalpha inhibitor treatment decreased to 0.70 (95% confidence interval 0.27-1.84).

Conclusion: The findings of this study indicate that TNFalpha inhibitor treatment that effectively reduces the inflammatory activity of RA is more likely to be beneficial than harmful with regard to the risk of heart failure, especially if there is no concomitant therapy with glucocorticoids or cyclooxygenase 2 inhibitors. Furthermore, the data suggest that TNFalpha inhibition does not increase the risk of worsening of prevalent heart failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab
  • Adult
  • Aged
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents / adverse effects*
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Cohort Studies
  • Cyclooxygenase 2 Inhibitors / adverse effects
  • Cyclooxygenase 2 Inhibitors / therapeutic use
  • Etanercept
  • Female
  • Germany
  • Glucocorticoids / adverse effects
  • Glucocorticoids / therapeutic use
  • Heart Failure / chemically induced*
  • Heart Failure / prevention & control*
  • Humans
  • Immunoglobulin G / adverse effects
  • Immunoglobulin G / therapeutic use
  • Infliximab
  • Interleukin 1 Receptor Antagonist Protein / adverse effects
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Prospective Studies
  • Receptors, Tumor Necrosis Factor / therapeutic use
  • Risk Factors
  • Severity of Illness Index
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Cyclooxygenase 2 Inhibitors
  • Glucocorticoids
  • Immunoglobulin G
  • Interleukin 1 Receptor Antagonist Protein
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Adalimumab
  • Etanercept