Metoprolol Succinate is Superior to Metoprolol Tartrate
For patients with heart failure and reduced ejection fraction, metoprolol succinate (extended-release) is definitively superior to metoprolol tartrate, as only the succinate formulation has proven mortality reduction in major clinical trials. 1
Critical Distinction: Only Succinate Has Mortality Benefit
The ACC/AHA guidelines explicitly recommend metoprolol succinate (sustained-release) as one of only three beta-blockers proven to reduce mortality in heart failure (along with bisoprolol and carvedilol), while metoprolol tartrate is not included in this recommendation 1
The MERIT-HF trial demonstrated that metoprolol succinate reduced all-cause mortality by 34%, sudden death by 41%, and death from progressive heart failure by 51% in patients with chronic heart failure 2, 3
Metoprolol tartrate has never been shown to reduce mortality in heart failure patients in large randomized controlled trials 1
Pharmacokinetic Advantages of Succinate
Metoprolol succinate provides consistent 24-hour beta-blockade with once-daily dosing, resulting in less fluctuation in plasma concentrations compared to the immediate-release tartrate formulation 3
The extended-release formulation maintains more stable autonomic balance throughout the day, with significantly greater parasympathetic activity (high-to-total variability ratio, P<0.05) and lower sympathetic activity (low-to-total variability ratio, P<0.05) compared to twice-daily tartrate 4
Blood pressure control is superior with metoprolol succinate, showing significantly lower systolic (P<0.0001) and diastolic (P<0.0005) blood pressure over 24 hours compared to equivalent doses of metoprolol tartrate 4
Clinical Efficacy in Heart Failure
In patients with heart failure and hypertension history, metoprolol succinate reduced total mortality by 39% (RR 0.61, P=0.0022), sudden death by 49% (RR 0.51, P=0.0022), and hospitalizations for worsening heart failure by 30% (P=0.015) 5
Despite using a fourfold higher starting dose of metoprolol succinate (25 mg once daily) compared to tartrate (6.25 mg twice daily), both formulations produced similar hemodynamic effects, but succinate's once-daily dosing offers practical advantages for initiation and titration 6
Dosing Recommendations
Start metoprolol succinate at 12.5-25 mg once daily and titrate to a target dose of 200 mg once daily at 2-week intervals in stable patients 1, 2
For metoprolol tartrate in acute myocardial infarction (the only indication where tartrate has evidence), start with 50 mg every 6 hours after initial IV dosing, then transition to 100 mg twice daily for maintenance 7
Renal Function Considerations
Neither formulation requires dose adjustment in renal impairment, as metoprolol is primarily eliminated by hepatic metabolism 7
Patients should maintain serum creatinine <2.0-2.5 mg/dL and potassium <5.0 mEq/L when initiating beta-blocker therapy in heart failure 1
Common Pitfall to Avoid
The COMET trial showed carvedilol had 17% greater mortality reduction than metoprolol, but this trial used metoprolol tartrate (not succinate), which likely explains the difference rather than true drug superiority 8, 9
Do not substitute metoprolol tartrate for succinate in heart failure patients, as the formulations are not therapeutically equivalent for this indication 1