Metoprolol: Comprehensive Clinical Guide
Indications
Metoprolol is indicated for hypertension, angina pectoris, heart failure with reduced ejection fraction (HFrEF), atrial fibrillation rate control, and secondary prevention post-myocardial infarction. 1, 2, 3
- Hypertension: Metoprolol tartrate 25–50 mg twice daily or metoprolol succinate 50–200 mg once daily, with maximum doses of 200 mg twice daily (tartrate) or 400 mg once daily (succinate) 1
- Angina pectoris: Target dose 200 mg daily of extended-release formulation, titrated gradually every 1–2 weeks 1
- Heart failure (HFrEF): Start at 12.5–25 mg once daily of metoprolol succinate, titrate every 2 weeks to target dose of 200 mg daily 1, 2
- Atrial fibrillation rate control: Metoprolol tartrate 25–100 mg twice daily (maximum 200 mg twice daily) or metoprolol succinate 50–400 mg once daily 1
- Post-MI secondary prevention: Target metoprolol succinate 200 mg once daily 1
Dosing Protocols
Immediate-Release (Metoprolol Tartrate)
- Initial dose: 25–50 mg twice daily 1
- Titration: Increase every 1–2 weeks based on heart rate and blood pressure response 1
- Maintenance: 100–200 mg twice daily 1
- Maximum: 200 mg twice daily (400 mg total daily) 1
Extended-Release (Metoprolol Succinate)
- Initial dose: 25–50 mg once daily (12.5–25 mg for heart failure) 1
- Titration: Increase every 1–2 weeks if well tolerated 1
- Target dose: 200 mg once daily for heart failure and post-MI 1
- Maximum: 400 mg once daily 1
Intravenous Administration
IV metoprolol carries significant risk and should be used with extreme caution. 4
- Standard protocol: 2.5–5 mg IV bolus over 1–2 minutes, repeat every 5 minutes as needed based on hemodynamic response 1
- Maximum total dose: 15 mg (three 5 mg boluses) 1
- Critical warning: The POISE trial demonstrated that early IV metoprolol increased mortality by 33% (3.1% vs 2.3%, p=0.03) and stroke by 2-fold (1.0% vs 0.5%, p=0.005), with an 11-per-1,000 increase in cardiogenic shock 4
- Transition to oral: Start metoprolol tartrate 25–50 mg every 6 hours beginning 15 minutes after the last IV dose 1
Absolute Contraindications
These conditions preclude metoprolol use regardless of clinical urgency: 1
- Decompensated heart failure with signs of pulmonary congestion, peripheral edema, or low cardiac output 1
- Second- or third-degree AV block without a functioning pacemaker, or PR interval >0.24 seconds 1
- Active asthma or severe reactive airway disease with current bronchospasm 1
- Cardiogenic shock or hemodynamic instability 1
- Symptomatic bradycardia (heart rate <50–60 bpm with dizziness, syncope, or hypoperfusion) 1
- Symptomatic hypotension (systolic BP <100 mmHg with symptoms) 1
- Pre-excitation syndromes (Wolff-Parkinson-White) in atrial fibrillation, as metoprolol may accelerate ventricular response 1
Perioperative Considerations
Routine initiation of beta-blockers immediately before noncardiac surgery increases harm and should be avoided. 4
Evidence from Major Trials
- POISE trial (2008): High-dose metoprolol (100 mg within 2–4 hours pre-op, then 100–200 mg daily) reduced nonfatal MI by 30% but increased total mortality by 33% and stroke by 100% 4
- Post-hoc analysis: Hypotension had the largest population-attributable risk for death and stroke 4
- DECREASE trials: Showed benefit when bisoprolol was started ≥1 week preoperatively with careful dose titration to heart rate targets, but these results have been questioned 4
Current Guideline Recommendations
- Continue existing beta-blockers perioperatively; abrupt discontinuation increases 1-year mortality 2.7-fold 1
- Do not initiate beta-blockers on the day of surgery or within 24 hours pre-operatively 4
- Hold parameters: Withhold dose if heart rate <45 bpm consistently, or delay 12 hours if heart rate 45–49 bpm 1
- Blood pressure threshold: Hold if systolic BP <100 mmHg with symptoms 1
Perioperative Dosing Regimens from Trials
- MaVS trial: Metoprolol tartrate 25–100 mg 2 hours pre-op, continued twice daily for up to 5 days—showed no benefit (10.2% vs 12% events, p=0.57) 4
- POBBLE trial: Metoprolol tartrate 25–50 mg twice daily starting 1 day pre-op plus IV 2–4 mg intraoperatively—no difference in outcomes (13% vs 15%, p=0.78) 4
Adverse Effects
Common (Dose-Related)
- Hypotension: Occurs in approximately 27% of patients receiving IV metoprolol; 15% with oral high-dose regimens 1
- Bradycardia: Approximately 16% develop heart rate <40 bpm with IV administration 1
- Fatigue and dizziness: Most frequently reported with chronic therapy 5, 6
- Bronchospasm: Even cardioselective beta-blockers can precipitate bronchospasm in susceptible patients 1
Serious
- Cardiogenic shock: Risk increases by 11 per 1,000 patients with early IV metoprolol, particularly in high-risk patients (age >70, systolic BP <120 mmHg, heart rate >110 or <60 bpm, Killip class >1) 1
- Stroke: Doubled in POISE trial with high-dose perioperative metoprolol 4
- Worsening heart failure: Can occur if initiated during decompensation 1
Withdrawal Syndrome
Abrupt discontinuation can cause severe exacerbation of angina, myocardial infarction, ventricular arrhythmias, and 50% mortality in one study. 1
- Taper protocol: Reduce dose by 25–50% every 1–2 weeks 1
- Monitor during taper: Watch for worsening heart failure symptoms, increased fatigue, or shortness of breath 1
Monitoring Parameters
Initial and Ongoing
- Heart rate: Target 50–60 bpm at rest unless limiting side effects occur 1
- Blood pressure: Check at each visit; target <130/80 mmHg for hypertension 1
- Clinical status: Assess for signs of worsening heart failure (dyspnea, edema, weight gain) 1
During IV Administration
- Continuous cardiac monitoring with frequent blood pressure checks after each bolus 1
- Auscultation for rales (pulmonary congestion) and bronchospasm 1
During Titration
- Reassess every 1–2 weeks when increasing dose 1
- Exercise tolerance: For atrial fibrillation, verify rate control during activity, not just at rest; consider 24-hour Holter monitoring 1
Alternative Agents
When Metoprolol Fails or Is Contraindicated
- Bisoprolol: Alternative beta-1 selective blocker; used in DECREASE trials with preoperative titration 4
- Carvedilol: Combined alpha- and beta-blockade; proven mortality benefit in heart failure; start 6.25 mg twice daily, titrate to maximum 25 mg twice daily 1
- Atenolol: Beta-1 selective; 25–100 mg daily, though cardiovascular benefit questioned in hypertension 1
- Diltiazem: Non-dihydropyridine calcium-channel blocker; 120–360 mg daily for rate control when beta-blockers contraindicated 1
- Verapamil: Alternative calcium-channel blocker; avoid in severe LV dysfunction 1
- Esmolol: Ultra-short-acting IV beta-blocker (half-life 10–30 minutes); loading dose 500 mcg/kg over 1 minute, maintenance 50–300 mcg/kg/min; preferred for high-risk patients requiring IV therapy 1
Special Populations
Women
- Lower dosing required: Women achieve 50–80% higher metoprolol exposure than men 1
- Optimal outcomes: Women with heart failure achieve best results at 50% of guideline-recommended doses, with 30% lower risk of death or hospitalization 1
- Elderly women: 15 mg produces similar exposure to 50 mg in young men; 25 mg equals 100 mg in young men 1
Pregnancy
- Safety profile: Considered first-line beta-blocker during pregnancy, though associated with intrauterine growth retardation 1
- Dosing: Use lowest recommended dose initially with adjustments based on clinical response 1
Common Pitfalls
- Giving full 15 mg IV dose rapidly: Significantly increases hypotension and bradycardia risk 1
- Initiating in decompensated heart failure: Wait until clinical stabilization (typically ~4 days) 1
- Using digoxin as sole agent for paroxysmal atrial fibrillation: Ineffective during physical activity 1
- Relying on resting ECG alone for rate control assessment: Many patients develop tachycardia during routine activities despite normal resting rates 1
- Abrupt discontinuation: Increases mortality 2.7-fold compared to continuous use 1
- Starting extended-release immediately after IV: Use immediate-release tartrate first to permit rapid titration 1