For heart failure with reduced ejection fraction, which is preferred, metoprolol tartrate or metoprolol succinate (beta blockers)?

Metoprolol Succinate is Preferred Over Metoprolol Tartrate for Heart Failure with Reduced Ejection Fraction

For patients with heart failure with reduced ejection fraction (HFrEF), metoprolol succinate (extended-release) is strongly preferred over metoprolol tartrate. 1

Rationale for Metoprolol Succinate Preference

• Metoprolol succinate (CR/XL) is specifically listed in the 2021 ACC Expert Consensus Decision Pathway for HFrEF treatment with a recommended starting dose of 12.5-25 mg daily and target dose of 200 mg daily 1
• The landmark MERIT-HF trial, which demonstrated mortality benefit in HFrEF, used metoprolol succinate CR/XL, not the tartrate formulation 2
• Metoprolol succinate provides more consistent 24-hour beta-blockade with once-daily dosing, which improves adherence and maintains steady drug levels 1
• European guidelines specifically mention metoprolol succinate CR in their dosing recommendations for HFrEF, distinguishing it from metoprolol tartrate 1

Evidence Supporting Metoprolol Succinate

• In the MERIT-HF trial, metoprolol succinate CR/XL demonstrated a 34% reduction in all-cause mortality, 38% reduction in cardiovascular mortality, and 41% reduction in sudden death compared to placebo 1, 2
• The target dose of metoprolol succinate used in MERIT-HF was 200 mg once daily, which is the recommended target dose in current guidelines 1, 2
• Only specific beta-blockers (bisoprolol, carvedilol, and metoprolol succinate) have demonstrated mortality benefit in HFrEF and are recommended in guidelines 1

Dosing Considerations

• Starting dose for metoprolol succinate: 12.5-25 mg once daily 1
• Target dose for metoprolol succinate: 200 mg once daily 1
• Titration should occur over weeks to months, with gradual increases as tolerated 1
• Metoprolol tartrate, if used, requires multiple daily dosing and has not been proven in large mortality trials for HFrEF 1

Clinical Considerations

• Beta-blockers should be initiated at low doses and gradually uptitrated to target doses shown to improve survival in clinical trials 1
• Many physicians underutilize beta-blockers in HFrEF by failing to reach target doses that have been shown to provide mortality benefit 1
• Women may experience greater reduction in blood pressure and heart rate during beta-blocker therapy and may have the lowest risk of death or heart failure hospitalization at half the guideline-recommended doses compared to men 1
• Beta-blockers should not be discontinued during acute decompensated heart failure unless severe hemodynamic instability occurs 1

Common Pitfalls to Avoid

• Using inadequate doses: The optimal dose of metoprolol succinate for HFrEF (200 mg daily) is higher than doses typically used for hypertension or angina (25-100 mg daily) 1
• Permanent dose reduction after temporary intolerance: In clinical trials, 40% of patients who required temporary dose reduction were subsequently restored to target doses, whereas in clinical practice, most dose reductions become permanent 1
• Failure to distinguish between formulations: Metoprolol tartrate and succinate are not interchangeable; the succinate formulation has the evidence base for HFrEF 1
• Stopping beta-blockers during hospitalization: Unless severe hemodynamic instability occurs, beta-blockers should be continued during heart failure exacerbations 1

While some comparative studies have suggested similar mortality outcomes between different beta-blockers (bisoprolol, carvedilol, and metoprolol succinate) in matched analyses 3, the evidence base specifically supports metoprolol succinate over metoprolol tartrate for HFrEF based on large randomized controlled trials and guideline recommendations.