What is the difference between metoprolol (beta-blocker) tartrate and metoprolol succinate in the management of hypertension and heart failure?

Metoprolol Succinate vs Tartrate: Critical Formulation Differences

For heart failure with reduced ejection fraction, metoprolol succinate is the only metoprolol formulation proven to reduce mortality and must be used exclusively—metoprolol tartrate is not an acceptable substitute in this population. 1, 2, 3

Key Pharmacokinetic Differences

Metoprolol Succinate (Extended-Release)

• Dosed once daily and provides consistent beta-1 blockade throughout the entire 24-hour dosing interval without marked peaks and troughs in plasma concentrations 2, 3, 4
• The controlled-release formulation releases drug at a constant rate over approximately 20 hours, independent of food intake and gastrointestinal pH 5, 4
• Maintains cardioselectivity at doses up to 200 mg daily due to even plasma concentrations 4

Metoprolol Tartrate (Immediate-Release)

• Requires twice-daily dosing due to shorter half-life and produces marked peaks and troughs in plasma concentrations 2, 3, 4
• Typical dosing is 25-100 mg twice daily for hypertension or angina 1, 2

Clinical Efficacy: Where the Formulations Diverge

Heart Failure with Reduced Ejection Fraction (HFrEF)

This is where formulation matters most for mortality outcomes:

• Metoprolol succinate demonstrated a 34% reduction in all-cause mortality in the MERIT-HF trial, with a 41% reduction in sudden death and 49% reduction in death from worsening heart failure 1, 3, 6, 7

• Target dose is 200 mg once daily (mean achieved dose in trials was 159 mg daily) 2, 3

• Start at 12.5-25 mg once daily and double the dose every 1-2 weeks if tolerated 1, 2, 3

• Metoprolol tartrate showed inferior outcomes compared to carvedilol in the COMET trial and is NOT the formulation proven to reduce mortality in heart failure 1, 3

• The commonly prescribed dose of metoprolol tartrate 50 mg twice daily was neither the dose nor formulation used in trials that demonstrated mortality reduction 1, 2

Hypertension

Both formulations are acceptable, with succinate offering convenience:

• Metoprolol succinate: 50-400 mg once daily 2
• Metoprolol tartrate: 25-100 mg twice daily 1, 2
• The dose of metoprolol used for hypertension (25-100 mg daily) is far lower than the target dose proven effective in heart failure (200 mg daily) 1

Post-Myocardial Infarction

Both formulations can be used, but succinate is preferred for long-term therapy with LV dysfunction:

• Initial therapy: metoprolol tartrate 50 mg every 6 hours for 48 hours after IV therapy 2
• Long-term maintenance: metoprolol succinate is preferred if LV dysfunction is present 3

Critical Clinical Pitfall to Avoid

Never substitute metoprolol tartrate for metoprolol succinate in heart failure patients—this is not simply a dosing conversion issue. 2, 3 The formulation difference translates to different clinical outcomes in heart failure, as the sustained-release properties of metoprolol succinate provide the consistent beta-1 blockade necessary for mortality reduction 1, 3

Physicians may mistakenly believe that doubling the tartrate dose (e.g., 100 mg twice daily) equals the succinate dose (200 mg once daily), but this ignores the pharmacokinetic differences that likely contribute to the divergent mortality outcomes 1, 2

Dosing Equivalence for Non-Heart Failure Indications

For hypertension or angina, a 100-mg metoprolol succinate tablet (containing 95 mg metoprolol succinate salt) is considered equivalent to 100 mg metoprolol tartrate in terms of beta-blocking activity 5

Monitoring During Titration

During uptitration of metoprolol succinate in heart failure patients, monitor for: 2

• Evidence of worsening heart failure symptoms or fluid retention
• Symptomatic hypotension (systolic BP <85 mmHg)
• Symptomatic bradycardia or heart rate <55 bpm
• Worsening renal function

If symptoms worsen: First increase diuretics or ACE inhibitors before reducing the beta-blocker dose; if hypotension occurs, reduce vasodilators first 2

Contraindications and Warnings

Both formulations share the same contraindications: 8

• Decompensated heart failure requiring IV inotropic therapy
• Second or third-degree heart block (PR interval >0.24 seconds)
• Active asthma or severe reactive airways disease
• Sinus bradycardia or sick sinus syndrome

Never abruptly discontinue either formulation in patients with coronary artery disease—taper over 1-2 weeks to avoid precipitating angina, myocardial infarction, or ventricular arrhythmias 2, 8