What is the best treatment approach for a patient with rheumatoid arthritis (RA) and heart failure (HF)?

Treatment Approach for Rheumatoid Arthritis with Heart Failure

For patients with rheumatoid arthritis and heart failure, non-TNF inhibitor biologics or targeted synthetic DMARDs are conditionally recommended over TNF inhibitors, especially in those with NYHA class III or IV heart failure. 1

Assessment of Heart Failure in RA Patients

• RA patients have almost twice the risk of heart failure compared to the general population, even after adjusting for ischemic heart disease 2
• Heart failure is more common in RA patients (3.9%) compared to osteoarthritis patients (2.3%) 3
• Risk factors for heart failure in RA include:
  • Traditional cardiovascular risk factors (hypertension, prior MI, diabetes, advanced age)
  • Disease-specific factors (persistent inflammation, high disease activity)
  • Medication-related factors (glucocorticoid use)

Treatment Recommendations Based on Heart Failure Status

For Patients with Established Heart Failure (NYHA Class III or IV):

1. First-line DMARD therapy:

   • Methotrexate remains the preferred initial DMARD for most RA patients 1
   • Monitor for hepatotoxicity, especially with other hepatotoxic medications 4

2. If inadequate response to conventional DMARDs:

   • Addition of a non-TNF inhibitor biologic DMARD or targeted synthetic DMARD is conditionally recommended over TNF inhibitors 1
   • Options include:
     • Abatacept
     • Rituximab (particularly beneficial in patients with previous lymphoproliferative disorders) 1
     • JAK inhibitors

3. For patients currently on TNF inhibitors who develop heart failure:

   • Switching to a non-TNF inhibitor biologic or tsDMARD is conditionally recommended over continuation of TNF inhibitor 1

For RA Patients Without Heart Failure:

• In the absence of pre-existing cardiovascular disease, the risk of developing heart failure is low (0.4%) 3
• TNF inhibitors may not increase the risk of heart failure in these patients and might even reduce cardiovascular mortality 5, 6

Glucocorticoid Considerations

• Use the minimal effective dose of glucocorticoids to minimize cardiovascular risk 7
• Glucocorticoids are associated with a dose-related gradient of heart failure risk:
  • 1-5 mg: HR 1.30 (95% CI 0.91 to 1.85)
  • ≥5 mg: HR 1.54 (95% CI 1.09 to 2.19) 6
• Consider short-term use (less than 3 months) as a bridge until DMARDs take effect 1

Monitoring Recommendations

1. Disease activity monitoring:

   • Use validated disease activity indices (DAS28, CDAI, SDAI) 8
   • Assess every 1-3 months in active disease and every 6-12 months in stable disease

2. Cardiovascular monitoring:

   • Regular assessment of cardiovascular risk factors
   • Echocardiography to assess cardiac function
   • BNP/NT-proBNP measurements to detect early heart failure

3. Treatment target:

   • Aim for remission or low disease activity
   • Effective control of inflammation may reduce heart failure risk

Clinical Pearls and Pitfalls

• Important caveat: The recommendation against TNF inhibitors in heart failure is based on trials in patients with heart failure without RA, where TNF inhibitors showed no benefit and possible worsening of disease 1
• Recent evidence suggests: TNF inhibitor treatment that effectively reduces RA inflammatory activity may actually be beneficial regarding heart failure risk, especially without concomitant glucocorticoids or COX-2 inhibitors 5
• Potential contradiction: While older studies raised concerns about TNF inhibitors in heart failure, more recent data suggests they may not worsen moderate heart failure and might protect against cardiovascular mortality in RA patients 7

By following these recommendations and carefully selecting appropriate DMARDs based on heart failure status, clinicians can effectively manage RA while minimizing cardiovascular risks in this challenging patient population.