What Disease-Modifying Antirheumatic Drugs (DMARDs) are safe to use in patients with atrial fibrillation?

DMARDs Safety in Atrial Fibrillation

Most conventional DMARDs can be safely used in patients with atrial fibrillation, with methotrexate appearing protective and leflunomide requiring caution based on recent evidence.

Key Safety Considerations

Methotrexate - Preferred DMARD

• Methotrexate demonstrates a protective effect against incident atrial fibrillation in patients with rheumatoid arthritis, with an adjusted odds ratio of 0.89 for new-onset AF 1
• This protective effect was particularly notable in male patients aged ≥50 years 1
• Methotrexate can be safely continued in patients with pre-existing AF without specific cardiac contraindications

Leflunomide - Use With Caution

• Leflunomide is associated with increased risk of incident atrial fibrillation (adjusted odds ratio 1.21) in patients with rheumatoid arthritis 1
• The risk increase was more pronounced in females and patients aged ≥50 years 1
• Consider alternative DMARDs in patients with pre-existing AF or multiple cardiovascular risk factors

Biologic DMARDs

• Adalimumab showed increased AF occurrence in patients aged ≥50 years 1
• Limited data exists for other biologics (TNF inhibitors, IL-6 inhibitors, JAK inhibitors) regarding AF safety
• No specific contraindications exist in current guidelines, but vigilance is warranted

Critical Management Principles for AF Patients on DMARDs

Anticoagulation Takes Priority

• All patients with AF and elevated stroke risk (CHA₂DS₂-VASc ≥2) require oral anticoagulation regardless of DMARD therapy 2
• Direct oral anticoagulants (DOACs) are preferred over warfarin for stroke prevention 2
• DMARD selection should not compromise anticoagulation adherence

Rate Control Medications

• Beta-blockers (metoprolol) or non-dihydropyridine calcium channel blockers (diltiazem, verapamil) are first-line for rate control in patients with preserved ejection fraction 2
• These rate control agents have no known adverse interactions with conventional DMARDs
• Beta-blockers are preferred in patients with reduced ejection fraction (LVEF ≤40%) 2

Rhythm Control Considerations

• If antiarrhythmic drugs are needed, amiodarone is recommended for patients with heart failure or structural heart disease 3
• Flecainide or propafenone can be used in patients without structural heart disease, left ventricular hypertrophy, or coronary artery disease 3
• Amiodarone has multiple drug interactions but no specific contraindications with DMARDs 3

Common Pitfalls to Avoid

Drug Interaction Monitoring

• Diltiazem and verapamil inhibit CYP3A4, potentially affecting methotrexate clearance 3
• Monitor for increased DMARD toxicity when combining with rate-control agents
• Adjust DMARD dosing if significant drug interactions are suspected

Bleeding Risk Assessment

• NSAIDs commonly used with DMARDs increase bleeding risk in anticoagulated patients
• Proton pump inhibitors are recommended for patients on anticoagulation who require NSAIDs 3
• Reassess bleeding risk regularly as it changes dynamically over time 4

Cardiovascular Risk Factor Management

• Hypertension, chronic kidney disease, and heart failure increase AF risk in DMARD-treated patients 1
• Aggressive management of these comorbidities is essential
• SGLT2 inhibitors are recommended for patients with diabetes to reduce cardiovascular events 3

Practical Algorithm

For patients with rheumatoid arthritis requiring DMARDs who have AF:

1. Ensure adequate anticoagulation based on CHA₂DS₂-VASc score 2
2. Prefer methotrexate as the conventional DMARD of choice 1
3. Avoid leflunomide if possible, especially in females and older patients 1
4. Establish rate control with beta-blockers or calcium channel blockers 2
5. Monitor cardiovascular risk factors including blood pressure, renal function, and heart failure symptoms 1
6. Reassess stroke and bleeding risk at regular intervals as these are dynamic 4

For new-onset AF in patients already on DMARDs:

1. Do not discontinue methotrexate - it may be protective 1
2. Consider switching from leflunomide to methotrexate or biologics 1
3. Initiate appropriate AF management including anticoagulation and rate/rhythm control 2
4. Evaluate for reversible AF triggers including thyroid disease, alcohol use, and electrolyte abnormalities