In an adult with heart failure with reduced ejection fraction and left ventricular ejection fraction of 20‑25 %, how quickly should metoprolol succinate be titrated and what is an appropriate starting dose?

Metoprolol Succinate Titration in HFrEF with LVEF 20-25%

Start metoprolol succinate at 12.5 mg once daily and titrate every 2 weeks to a target dose of 200 mg once daily, or to the maximally tolerated dose. 1

Starting Dose

• Begin with 12.5 mg once daily for patients with NYHA class III-IV symptoms (which is likely given the severely reduced LVEF of 20-25%) 2, 3
• Patients with NYHA class II symptoms can start at 25 mg once daily 2, 3
• The extended-release formulation provides consistent beta-1 blockade over 24 hours without marked peaks and troughs 4

Titration Schedule

• Increase the dose every 2 weeks if the lower dose has been well tolerated 1
• The ACC Expert Consensus Decision Pathway specifically states that GDMT therapies should be adjusted no more frequently than every 2 weeks to target doses 1
• Gradual incremental increases minimize adverse effects while achieving therapeutic benefit 1

Target Dose

• The target dose is 200 mg once daily for all patients who can tolerate this dose 5, 2, 3
• Aim for at least 50% of the target dose (100 mg daily) as a minimum goal, as doses below this threshold may result in worse clinical outcomes 1
• The dose-response relationship demonstrates that higher doses within the therapeutic range provide superior mortality and morbidity benefits 1

Typical Titration Pathway

The standard progression over 6-8 weeks is: 2, 3

• Week 0-2: 12.5 mg once daily
• Week 2-4: 25 mg once daily
• Week 4-6: 50 mg once daily
• Week 6-8: 100 mg once daily
• Week 8-10: 150 mg once daily
• Week 10+: 200 mg once daily (target)

Critical Precautions for Severely Reduced LVEF

• Ensure the patient is euvolemic and hemodynamically stable before initiating beta-blocker therapy 1
• Beta-blocker therapy should only be initiated after optimization of volume status and successful discontinuation of intravenous diuretics, vasodilators, and inotropic agents 1
• Use extreme caution if the patient required inotropes during hospitalization 1
• Monitor closely for signs of worsening heart failure, bradycardia, and hypotension during each titration step 6

Common Pitfalls to Avoid

• Never abruptly discontinue beta-blocker therapy, as this can precipitate acute heart failure exacerbation 7, 6
• Do not use metoprolol tartrate (immediate-release) instead of metoprolol succinate (extended-release), as only the succinate formulation has proven mortality benefits in HFrEF 7, 6
• Avoid titrating faster than every 2 weeks, even if the patient appears to tolerate lower doses well 1
• Do not stop titration prematurely—make every effort to reach the target dose of 200 mg daily, as this provides maximal mortality benefit 1