Metoprolol Succinate is Preferred Over Metoprolol Tartrate
For patients requiring beta-blockade, metoprolol succinate (extended-release) is the preferred formulation, particularly in heart failure with reduced ejection fraction (HFrEF), due to proven mortality reduction and superior pharmacokinetic properties. 1, 2
Heart Failure with Reduced Ejection Fraction (HFrEF)
Metoprolol succinate is the only metoprolol formulation proven to reduce mortality in HFrEF and should be used exclusively in this population. 1, 2
- The ACC/AHA explicitly recommends sustained-release metoprolol succinate (along with bisoprolol and carvedilol) as one of three beta-blockers proven to reduce mortality in HFrEF patients with LVEF ≤40%. 1
- Metoprolol succinate demonstrated a 34% relative risk reduction in all-cause mortality in the MERIT-HF trial, along with a 41% reduction in sudden death and 45% reduction in hospitalizations for worsening heart failure. 2, 3, 4
- Critical pitfall: Metoprolol tartrate should never be substituted for metoprolol succinate in heart failure patients, as the formulation difference translates to different clinical outcomes. 2
- Metoprolol tartrate showed inferior outcomes compared to carvedilol in the COMET trial and is not the formulation with proven mortality benefit. 2
Dosing for HFrEF
- Start metoprolol succinate at 12.5-25 mg once daily and titrate to a target dose of 200 mg once daily. 2
- The mean dose achieved in clinical trials was 159 mg once daily. 2
- Initiate only after volume optimization and discontinuation of IV diuretics, vasodilators, and inotropes. 1
Pharmacokinetic Advantages of Metoprolol Succinate
Metoprolol succinate provides consistent 24-hour beta-1 blockade with once-daily dosing, while metoprolol tartrate produces marked peaks and troughs requiring twice-daily administration. 2, 5
- Metoprolol succinate delivers drug at a near-constant rate for approximately 20 hours, independent of food intake and gastrointestinal pH. 5
- This results in even plasma concentrations over 24 hours without the fluctuations seen with immediate-release formulations. 5, 3
- Consistent beta-1 blockade is maintained throughout the entire dosing interval while preserving cardioselectivity at doses up to 200 mg daily. 5, 3
- Metoprolol tartrate requires twice-daily dosing (BID) due to its immediate-release formulation. 1
Other Indications Where Both Formulations Are Acceptable
Atrial Fibrillation Rate Control
Both formulations are listed in ACC/AHA/HRS guidelines for rate control in atrial fibrillation, though metoprolol succinate offers once-daily convenience. 1, 2
- IV metoprolol tartrate: 2.5-5.0 mg IV bolus over 2 minutes; up to 3 doses for acute rate control. 1
- Oral metoprolol tartrate: 25-100 mg twice daily for maintenance. 1
- Oral metoprolol succinate: 50-400 mg once daily for maintenance. 1
Hypertension
Both formulations are effective for hypertension, with metoprolol succinate preferred for once-daily dosing convenience. 2, 6
Post-Myocardial Infarction
Both formulations can be used post-MI, though metoprolol succinate is preferred for long-term therapy when left ventricular dysfunction is present. 2
Perioperative Beta-Blockade
Data suggest long-acting beta-blockade (including metoprolol succinate) may be superior to short-acting formulations when initiated before surgery, though the POISE trial showed increased stroke risk with aggressive perioperative metoprolol succinate dosing. 1
Clinical Algorithm for Formulation Selection
- HFrEF (LVEF ≤40%): Use metoprolol succinate exclusively—never substitute tartrate. 1, 2
- Atrial fibrillation rate control: Either formulation acceptable; prefer succinate for once-daily dosing. 1
- Hypertension: Either formulation acceptable; prefer succinate for once-daily dosing. 2, 6
- Post-MI with LV dysfunction: Prefer metoprolol succinate for long-term therapy. 2
- Acute IV administration needed: Use metoprolol tartrate IV formulation. 1