What is the appropriate dosing and management of metoprolol (metoprolol ER) for a patient with a history of cardiovascular disease, such as hypertension or heart failure?

Metoprolol ER Dosing and Management

Initial Dosing Strategy

For hypertension, start metoprolol succinate (extended-release) at 50 mg once daily, titrating every 1-2 weeks to a maximum of 400 mg daily based on blood pressure response, with a target BP <130/80 mmHg. 1, 2

For heart failure with reduced ejection fraction (HFrEF), initiate metoprolol succinate at 12.5-25 mg once daily, doubling the dose every 2 weeks as tolerated to reach the target dose of 200 mg daily. 1, 2, 3

Formulation-Specific Considerations

• Metoprolol succinate (extended-release) is the preferred formulation for heart failure, as it was the formulation proven effective in the MERIT-HF trial, which demonstrated a 34% reduction in all-cause mortality. 4, 2, 3

• Metoprolol tartrate (immediate-release) requires twice-daily dosing at 50-200 mg per day for hypertension, while the extended-release formulation allows convenient once-daily administration. 1, 2

• Bisoprolol and metoprolol succinate are the preferred beta-blockers in patients with HFrEF, avoiding abrupt cessation in all cases. 1

Critical Contraindications Before Initiation

Absolute contraindications include: 1, 2, 5

• Signs of heart failure, low output state, or decompensated heart failure
• Second or third-degree heart block without a functioning pacemaker
• Active asthma or reactive airways disease
• Cardiogenic shock
• Marked sinus bradycardia (HR <60 bpm with symptoms)
• Systolic BP <100 mmHg with symptoms
• PR interval >0.24 seconds

Risk Factors Requiring Caution

• Age >70 years combined with systolic BP <120 mmHg increases cardiogenic shock risk. 2, 5
• Sinus tachycardia >110 bpm or heart rate <60 bpm are additional risk factors. 2

Titration Protocol and Monitoring

Heart Failure Titration

• Start at 12.5-25 mg once daily and double the dose every 2 weeks if well tolerated. 2, 3
• Target dose is 200 mg daily, though at least 50% of target (100 mg daily) should be achieved for optimal outcomes. 2
• Monitor heart rate (target 55-60 bpm at rest), blood pressure (maintain systolic >90 mmHg), and clinical status at each visit. 4, 2

Hypertension Titration

• Increase dose every 1-2 weeks based on blood pressure response. 1, 2
• Target BP reduction to <130/80 mmHg, ideally achieving at least 20/10 mmHg reduction. 2
• Beta-blockers are not recommended as first-line agents for uncomplicated hypertension unless the patient has ischemic heart disease or heart failure. 1

Hold Parameters and Dose Adjustment

Hold metoprolol immediately if: 2

• Symptomatic bradycardia (HR <50-60 bpm with dizziness, lightheadedness, or syncope)
• Systolic BP <90 mmHg with symptoms of hypoperfusion
• Signs of decompensated heart failure develop
• Second or third-degree heart block appears

Dose Reduction Strategy

• For symptomatic bradycardia or hypotension, reduce the dose by 50% rather than discontinuing completely, as abrupt cessation increases mortality risk 2.7-fold. 2
• Temporarily increase diuretics or adjust other vasodilators before reducing metoprolol in heart failure patients. 4, 2
• Never abruptly discontinue metoprolol, as this can cause severe exacerbation of angina, myocardial infarction, and ventricular arrhythmias with up to 50% mortality in some studies. 2

Special Population Considerations

Women

• Women achieve 50-80% higher metoprolol exposure than men, resulting in greater heart rate and blood pressure reduction. 2
• Consider starting at 50% of standard doses in women (e.g., 12.5 mg daily instead of 25 mg) to reduce adverse effects while maintaining efficacy. 2
• Women with heart failure achieved optimal outcomes at 50% of guideline-recommended doses with 30% lower risk of death or hospitalization. 2

Elderly Patients (>65 years)

• Initiate at the lowest recommended dose with cautious gradual titration due to age-related changes in drug metabolism. 4
• For frail elderly patients >80 years with multiple comorbidities, consider starting at 3.125 mg twice daily (tartrate) or 12.5 mg daily (succinate). 4

Hepatic Impairment

• Metoprolol blood levels increase substantially in hepatic impairment. 5
• Initiate at low doses with cautious gradual titration according to clinical response. 5

Renal Impairment

• No dose adjustment required for renal impairment. 5

Common Adverse Effects and Management

• Dizziness/syncope occurs in 12-19% of patients, most frequently in the first weeks of treatment. 4
• Hypotension affects 8.6% of patients, particularly those with baseline systolic BP <100 mmHg. 4
• Fatigue/asthenia is reported in 25-33% of patients. 4
• At 12.5 mg/day, adverse event rate is 45.5% compared to 42.2% with placebo, with 13.7% discontinuation rate. 4

Management Strategies

• Most adverse effects are mild and occur early in treatment, resolving with continued therapy. 4
• Maintain systolic BP >90 mmHg to manage symptomatic hypotension. 4
• Monitor for worsening heart failure symptoms, bronchospasm, and signs of excessive beta-blockade. 2

Critical Clinical Pitfalls to Avoid

• Never combine metoprolol with another beta-blocker (e.g., propranolol), as this causes additive beta-blockade effects leading to significant bradycardia, heart block, and hypotension. 6
• Do not use metoprolol tartrate for heart failure—only metoprolol succinate has proven mortality benefit. 4, 2
• Avoid routine use with non-dihydropyridine calcium channel blockers (diltiazem, verapamil) due to increased risk of bradycardia and heart block. 1
• Do not administer IV metoprolol in acute MI patients with signs of hemodynamic instability, as the COMMIT trial showed increased cardiogenic shock risk. 2