What is the next step in managing a patient with new‑onset atrial fibrillation who did not respond to metoprolol?

Management of New-Onset Atrial Fibrillation After Metoprolol Failure

Add Diltiazem or Digoxin to Metoprolol for Combination Rate Control

If metoprolol alone fails to achieve adequate rate control in new-onset atrial fibrillation, add either intravenous diltiazem or digoxin to the existing beta-blocker regimen. Combination therapy with digoxin plus a beta-blocker provides superior heart-rate control both at rest and during exercise compared with either drug alone. 1, 2

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Step 1: Verify Hemodynamic Stability and Assess for Immediate Cardioversion

• Perform immediate synchronized electrical cardioversion (≥200 J biphasic) without waiting for anticoagulation if the patient exhibits hemodynamic instability—defined as symptomatic hypotension (systolic BP <90 mmHg), acute pulmonary edema, ongoing chest pain, altered mental status, or shock. 1, 3
• If the patient remains hemodynamically stable (adequate blood pressure, no acute heart failure, no chest pain), proceed with pharmacologic rate control rather than emergent cardioversion. 1, 3

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Step 2: Confirm Left Ventricular Function to Guide Drug Selection

• Obtain or review a transthoracic echocardiogram to determine left ventricular ejection fraction (LVEF) before escalating therapy, because drug choice depends critically on whether LVEF is preserved (>40%) or reduced (≤40%). 3, 2
• For LVEF >40% (preserved ejection fraction): both diltiazem and digoxin are safe options to add to metoprolol. 1, 3
• For LVEF ≤40% (reduced ejection fraction or heart failure): add digoxin only; avoid diltiazem and verapamil because of their negative inotropic effects, which may worsen hemodynamics. 1, 3, 2

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Step 3: Add Intravenous Diltiazem (Preferred for Preserved EF)

• Administer diltiazem 0.25 mg/kg IV over 2 minutes (typically 15–20 mg), followed by a second bolus of 0.35 mg/kg if needed, then start a continuous infusion at 5–15 mg/h. 1, 3
• Diltiazem achieves rate control more rapidly than metoprolol: 63% of patients reach a heart rate <100 bpm at 30 minutes with diltiazem versus 27% with metoprolol alone (p<0.001). 4
• Diltiazem reduces heart rate by a mean of 33 bpm at 30 minutes compared with 20 bpm for metoprolol (p<0.001), and achieves target rate control in a median of 13 minutes versus 27 minutes for metoprolol (p=0.009). 5, 4
• Meta-analysis of 11 randomized trials and 19 observational studies confirms that IV diltiazem is significantly more effective than IV metoprolol for rate control (RR 1.30,95% CI 1.09–1.56, p=0.003) and produces a greater ventricular rate reduction (mean difference −14.55 bpm, 95% CI −16.93 to −12.16, p<0.00001). 6
• Safety profile: Diltiazem carries a slightly increased risk of hypotension (RR 1.43,95% CI 1.14–1.79, p=0.002) but no increased risk of bradycardia or other adverse events compared with metoprolol. 6
• Do not combine diltiazem with metoprolol in patients with reduced ejection fraction (LVEF ≤40%) because dual AV-nodal blockade may precipitate excessive bradycardia and worsen heart failure. 3, 2

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Step 4: Add Digoxin (Preferred for Reduced EF or as Alternative)

• Administer digoxin 0.25 mg IV, with repeat doses up to a cumulative maximum of 1.5 mg within 24 hours. 3
• Digoxin is the only safe add-on agent for patients with LVEF ≤40% or overt heart failure, because it does not depress myocardial contractility. 1, 3
• Combination of digoxin with metoprolol is reasonable and provides better rate control at rest and during exercise than either drug alone (Class IIa, Level B). 1, 2
• Critical pitfall: Digoxin alone is ineffective for acute rate control in paroxysmal atrial fibrillation, especially during exercise or sympathetic surges, because its onset is slow; it must be combined with a beta-blocker or calcium-channel blocker. 3, 2

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Step 5: Target Heart Rate Goals

• Aim for a lenient resting heart rate <110 bpm as the initial target for most patients. 1, 3
• Pursue stricter control (<80 bpm) only if symptoms persist despite lenient control. 1, 3
• Assess heart rate during exertion, not just at rest, because many patients exhibit inadequate rate control during activity despite acceptable resting rates. 3, 2

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Step 6: Initiate or Continue Anticoagulation

• Calculate the CHA₂DS₂-VASc score immediately and initiate oral anticoagulation for all patients with a score ≥2 (men) or ≥3 (women). 1, 3
• Prescribe a direct oral anticoagulant (apixaban, rivaroxaban, edoxaban, or dabigatran) as first-line therapy over warfarin, except in patients with mechanical heart valves or moderate-to-severe mitral stenosis. 3, 2
• For atrial fibrillation lasting >48 hours or of unknown duration, provide therapeutic anticoagulation for at least 3 weeks before any elective cardioversion and continue for a minimum of 4 weeks afterward. 3, 2
• Anticoagulation decisions are based on stroke risk (CHA₂DS₂-VASc score), not on whether rate control is achieved or sinus rhythm is restored. 3, 2

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Step 7: Consider Rhythm Control Only in Select Patients

• Rhythm control (cardioversion or antiarrhythmic drugs) is appropriate for patients who remain symptomatic despite adequate rate control, younger patients (<65 years) with new-onset atrial fibrillation, those with rate-related cardiomyopathy, or hemodynamically unstable patients. 3, 2
• Rhythm control does not reduce mortality compared with rate control and is associated with higher hospitalization and adverse drug-effect rates in older patients. 3, 2
• For patients without structural heart disease, flecainide or propafenone are first-line antiarrhythmic agents; for those with heart failure or LVEF ≤40%, amiodarone is the only safe option. 3, 2

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Common Pitfalls to Avoid

• Do not rely on digoxin alone for acute rate control; it should always be combined with metoprolol or diltiazem. 3, 2
• Do not administer diltiazem or verapamil in patients with LVEF ≤40% or decompensated heart failure, as they may exacerbate hemodynamic compromise. 1, 3
• Do not combine metoprolol with diltiazem except under specialist supervision with continuous ECG monitoring, because dual AV-nodal blockade can cause excessive bradycardia. 3
• Do not discontinue anticoagulation solely because sinus rhythm has been achieved; stroke risk is determined by CHA₂DS₂-VASc score, not rhythm status. 3, 2
• In Wolff-Parkinson-White syndrome with atrial fibrillation, avoid all AV-nodal blockers (metoprolol, diltiazem, digoxin, adenosine) because they may accelerate ventricular response and precipitate ventricular fibrillation; use IV procainamide instead. 3, 2

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Summary Algorithm

1. Hemodynamically unstable? → Immediate cardioversion 1, 3
2. Hemodynamically stable → Check LVEF 3, 2
   • LVEF >40%: Add IV diltiazem (0.25 mg/kg bolus, then infusion) 1, 3, 6
   • LVEF ≤40%: Add IV digoxin (0.25 mg, repeat as needed) 1, 3
3. Target resting HR <110 bpm (lenient control) 1, 3
4. Initiate anticoagulation based on CHA₂DS₂-VASc score 3, 2
5. Consider rhythm control only if symptomatic despite rate control 3, 2