What are the recommended initial dose, titration schedule, contraindications, and alternative therapies for metoprolol in an adult with hypertension, chronic heart failure with reduced ejection fraction, and atrial fibrillation?

Metoprolol in Adults with Hypertension, Heart Failure with Reduced Ejection Fraction, and Atrial Fibrillation

Recommended Initial Dose and Formulation

For this patient with multiple cardiovascular conditions, initiate metoprolol succinate extended-release at 12.5–25 mg once daily, targeting the heart failure indication first, as this provides the greatest mortality benefit. 1

• Only metoprolol succinate extended-release (CR/XL) reduces mortality in heart failure—metoprolol tartrate has not demonstrated this benefit and must not be substituted 2, 1, 3
• The starting dose of 12.5 mg is appropriate for NYHA class III–IV symptoms, while 25 mg is used for NYHA class II 1, 4
• This formulation simultaneously addresses all three conditions: heart failure, hypertension, and atrial fibrillation rate control 2, 1

Titration Schedule

Double the dose every 2 weeks if the previous dose is well tolerated, following this progression: 12.5 mg → 25 mg → 50 mg → 100 mg → 200 mg once daily. 1, 4

• The target dose is 200 mg once daily, which achieved a 34% reduction in all-cause mortality in the MERIT-HF trial 1, 3, 4
• If the full target cannot be reached, aim for at least 50% of target dose (100 mg daily minimum), as dose-response relationships exist for mortality benefit 1
• At each titration visit, monitor heart rate, blood pressure, signs of congestion (lung auscultation, peripheral edema), and body weight 1

Managing Adverse Effects During Titration

• For worsening congestion: First double the diuretic dose; only halve the metoprolol dose if increasing diuretic fails 1
• For marked fatigue or symptomatic bradycardia (<50 bpm with symptoms): Halve the metoprolol dose 1
• For symptomatic hypotension: First reduce or eliminate vasodilators (nitrates, calcium channel blockers); second, reduce diuretics if no congestion present; third, temporarily reduce metoprolol by 50% only if above measures fail 1

Absolute Contraindications

Do not initiate or continue metoprolol if any of the following are present:

• Current or recent (within 4 weeks) decompensated heart failure requiring hospitalization 1, 5
• Second- or third-degree AV block without a functioning pacemaker 2, 1, 5
• PR interval >0.24 seconds 5
• Active asthma or severe reactive airway disease with current bronchospasm 1, 5
• Symptomatic bradycardia (heart rate <50 bpm with dizziness, syncope, or hypoperfusion) 1
• Systolic blood pressure <100 mmHg with symptoms 1
• Sick sinus syndrome without a pacemaker 1

Alternative Beta-Blocker Therapies

If metoprolol succinate is not tolerated, consider these evidence-based alternatives:

Bisoprolol

• Start at 1.25 mg once daily, titrate every 2–4 weeks to target dose of 10 mg once daily 1
• Proven mortality reduction in heart failure (34% relative risk reduction) 1
• Once-daily dosing with more consistent beta-blockade 1

Carvedilol

• Start at 3.125 mg twice daily, titrate every 1–2 weeks to target dose of 25–50 mg twice daily 1
• Combined alpha-1 and beta-blockade provides additional vasodilation 1
• Proven mortality reduction of 34–65% compared to placebo 1

These three beta-blockers (metoprolol succinate, bisoprolol, carvedilol) are the only ones with proven mortality reduction in heart failure—this is not a class effect. 2, 1

Alternative Rate-Control Agents (If Beta-Blockers Contraindicated)

Diltiazem

• Dosing: 120–360 mg daily (extended-release) 2
• Critical warning: Avoid in heart failure with reduced ejection fraction, as it worsens outcomes 2, 1
• Only consider if beta-blockers are absolutely contraindicated and heart failure is well-compensated 2

Digoxin

• Dosing: 0.0625–0.25 mg daily 2
• Renally eliminated; adjust for renal function 2
• Important limitation: Reduces hospitalizations but does not reduce mortality 2
• Increased mortality at plasma concentrations >1.2 ng/mL 2
• Reserve as adjunctive therapy when beta-blockers alone provide insufficient rate control 2

Amiodarone

• Dosing: Loading 6–10 g over 2–4 weeks, maintenance 100–200 mg daily 2
• Generally reserved for refractory cases due to significant toxicity profile 2

Critical Clinical Pearls

• Never abruptly discontinue metoprolol—this causes rebound hypertension, myocardial ischemia, infarction, and ventricular arrhythmias, with a 2.7-fold increased risk of 1-year mortality 1
• Some beta-blocker is better than no beta-blocker when target doses cannot be achieved 2, 1
• Beta-blockers are not first-line for hypertension alone unless the patient has ischemic heart disease or heart failure—both present in this case 1
• For atrial fibrillation rate control, target resting heart rate <80 bpm (strict control) or <110 bpm (lenient control) 2
• Cardioselective agents (bisoprolol, metoprolol) are preferred if bronchospastic disease is present, though active asthma remains an absolute contraindication 1