Is formoterol (a beta2-agonist) safe to use in patients with atrial fibrillation?

Formoterol Should Be Avoided in Patients with Atrial Fibrillation

Beta-adrenergic agonists like formoterol are not recommended in patients with atrial fibrillation due to their potential to worsen arrhythmias and cause adverse cardiovascular effects. 1

Mechanism of Concern

Formoterol is a long-acting beta-2 agonist (LABA) primarily used for bronchodilation in respiratory conditions. However, it poses several risks in patients with AF:

1. Chronotropic effects: Beta-2 agonists can increase heart rate, potentially worsening rate control in AF patients
2. Electrolyte disturbances: Formoterol can reduce serum potassium levels (hypokalemia) 2
   • FDA data shows formoterol can decrease potassium by 0.68 ± 0.4 mEq/L after high doses
   • Hypokalemia can exacerbate cardiac arrhythmias including AF
3. QT interval effects: At high doses, formoterol can prolong QT interval 2

Guideline Recommendations

The 2006 ACC/AHA/ESC guidelines for AF management explicitly state:

"Beta blockers, sotalol, propafenone, and adenosine are not recommended in patients with obstructive lung disease who develop AF." 1

This recommendation extends to beta-agonists like formoterol, as they have opposing pharmacological actions to beta-blockers and can potentially worsen arrhythmias.

Alternative Management Approaches

For patients with both AF and respiratory disease requiring bronchodilation:

1. First-line agents: Non-dihydropyridine calcium channel antagonists (diltiazem or verapamil) are recommended for rate control in patients with obstructive pulmonary disease who develop AF 1

2. Primary therapeutic measures: Correction of hypoxemia and acidosis should be the first step for patients who develop AF during acute pulmonary illness or COPD exacerbation 1

3. Cardioversion: For hemodynamically unstable patients with pulmonary disease and AF, direct-current cardioversion should be attempted 1

Research Evidence on Formoterol and Cardiac Safety

While some studies suggest formoterol may have acceptable cardiac safety in certain COPD populations 3, these studies typically exclude patients with significant arrhythmias:

• In patients with preexisting cardiac arrhythmias and hypoxemia, formoterol (especially at higher doses) has been shown to increase heart rate and cardiac arrhythmias compared to placebo 4
• Formoterol 24 μg significantly reduced plasma potassium levels for up to 9 hours, which can potentially worsen arrhythmias 4

Clinical Approach

For patients with both AF and respiratory disease requiring bronchodilation:

1. Avoid beta-adrenergic agonists including formoterol
2. Consider anticholinergic bronchodilators as an alternative
3. Use calcium channel blockers (diltiazem or verapamil) for rate control in AF with COPD
4. Monitor electrolytes closely if beta-agonists must be used temporarily
5. Consider cardiology consultation for complex cases

Important Caveats

• Even at recommended doses, formoterol can cause hypokalemia and potentially worsen arrhythmias
• The risk is dose-dependent, with higher doses carrying greater risk
• Patients with hypoxemia are at particularly high risk for adverse effects from beta-agonists
• Concomitant use of other medications that can prolong QT interval should be avoided

In conclusion, formoterol should be avoided in patients with atrial fibrillation, and alternative bronchodilator strategies should be employed whenever possible.