What are the differences between beta blockers, such as metoprolol (Lopressor) and atenolol (Tenormin), in terms of pharmacological properties and clinical uses?

Comparison of Beta Blockers: Metoprolol vs. Atenolol

Direct Answer

Metoprolol is the preferred beta blocker over atenolol for most cardiovascular indications, particularly in heart failure with reduced ejection fraction (HFrEF), post-myocardial infarction, and hypertension, based on superior evidence for mortality reduction and more favorable pharmacokinetic properties. 1, 2

Key Pharmacological Differences

Selectivity

• Both metoprolol and atenolol are beta-1 selective (cardioselective) agents, preferentially blocking cardiac beta-1 receptors over bronchial/vascular beta-2 receptors at lower doses 1, 3, 4
• Neither agent has intrinsic sympathomimetic activity (ISA), which is preferred for post-MI and heart failure patients 1
• At higher concentrations, both lose selectivity and block beta-2 receptors 3, 4, 5

Pharmacokinetics: Critical Differences

Metoprolol:

• Undergoes extensive hepatic metabolism via CYP2D6 with ~50% oral bioavailability due to first-pass metabolism 4
• Plasma half-life: 3-7 hours for immediate release formulation 4
• Highly lipophilic, crosses blood-brain barrier 4
• Metoprolol succinate (extended-release) allows once-daily dosing at 50-200 mg 1, 2
• Women have 50-100% higher exposure due to slower CYP2D6 metabolism, requiring lower doses 1

Atenolol:

• Undergoes minimal hepatic metabolism (<10%), primarily renally excreted unchanged 3
• Plasma half-life: 6-7 hours 3
• Hydrophilic, minimal CNS penetration 3
• Requires dose adjustment in renal impairment (creatinine clearance <35 mL/min/1.73m²) 3
• Only 6-16% protein bound vs. higher binding for metoprolol 3
• Duration of action: 24 hours despite shorter half-life, allowing once-daily dosing 3, 6

Clinical Efficacy by Indication

Post-Myocardial Infarction

• Metoprolol has demonstrated mortality benefit post-MI in multiple trials 1, 7
• Atenolol was studied in GUSTO-I but showed no significant mortality reduction in systematic reviews 1
• Avoid early IV beta blockers in hemodynamically unstable patients or those at high risk for cardiogenic shock (older age, female sex, higher Killip class, lower BP, higher HR) 1
• Initiate oral beta blockers within first 24 hours in stable patients without contraindications 1

Heart Failure with Reduced Ejection Fraction (HFrEF)

• Metoprolol succinate is a guideline-recommended agent with proven mortality benefit in MERIT-HF trial 1, 2, 7
• Atenolol has NOT been studied or proven effective in HFrEF and should not be used 1, 2
• Bisoprolol and carvedilol are alternative evidence-based options for HFrEF 1, 2

Hypertension

• Both agents effectively lower blood pressure, but atenolol's cardiovascular benefit has been questioned in hypertension trials 1
• Metoprolol provides more consistent 24-hour BP control with extended-release formulation 1, 2, 6
• Atenolol 100 mg once daily was more effective than metoprolol tartrate 100 mg once daily at 25 hours post-dose, likely due to metoprolol's shorter half-life requiring twice-daily dosing for standard formulation 6
• Beta blockers are NOT first-line for primary hypertension per current guidelines 1, 8

Angina Pectoris

• Both agents are effective for chronic stable angina 1
• Metoprolol: 50-200 mg twice daily (tartrate) or 50-200 mg once daily (succinate) 1, 2
• Atenolol: 50-200 mg once daily 1

Dosing Recommendations

Metoprolol

• Metoprolol tartrate: 100-200 mg daily in 2 divided doses 1, 2
• Metoprolol succinate: 50-200 mg once daily 1, 2
• Initial hypertension dosing: 25-50 mg twice daily (tartrate) or 50-100 mg once daily (succinate) 2
• Women may require 25-50% lower doses due to higher drug exposure 1

Atenolol

• Standard dosing: 50-200 mg once daily 1
• Renal dosing adjustments required: 50 mg daily if CrCl 15-35 mL/min; 50 mg every other day if CrCl <15 mL/min 3

Special Populations

Respiratory Disease

• Both are relatively safe in mild-moderate asthma/COPD due to beta-1 selectivity 1, 2
• Use lowest effective dose and monitor pulmonary function 1, 5
• Metoprolol is specifically recommended by ACC/AHA for patients with respiratory conditions requiring beta blockade 2

Renal Impairment

• Atenolol requires significant dose reduction as >85% is renally excreted 3
• Metoprolol does NOT require renal dose adjustment due to hepatic metabolism 4

Women

• Metoprolol exposure is 50-100% higher in women, persisting after weight normalization 1
• Women experience more adverse drug reactions with CYP2D6-metabolized beta blockers (metoprolol, carvedilol, propranolol) 1
• Consider starting at lower doses in women to reduce ADR risk 1

Contraindications (Both Agents)

• Marked first-degree AV block (PR >0.24 seconds) 1, 2
• Second or third-degree AV block without pacemaker 1, 2
• Cardiogenic shock or decompensated heart failure 1, 2
• Severe bradycardia (HR <50-60 bpm) 1
• Hypotension or hemodynamic instability 1

Discontinuation

• Both require gradual tapering to avoid rebound hypertension, worsening angina, or MI 2
• Metoprolol: reduce dose by 25-50% every 1-2 weeks 2
• Never abruptly discontinue either agent 1, 2

Monitoring

• Blood pressure and heart rate should be monitored regularly with both agents 2
• Assess adequacy of beta blockade by exercise heart rate response 1
• Monitor for signs of heart failure, bronchospasm, and bradycardia 1

Common Pitfalls

• Do not use atenolol for heart failure—it lacks evidence and is not guideline-recommended 1, 2
• Do not assume all beta blockers are interchangeable—mortality benefits are agent-specific 7, 8
• Do not use metoprolol tartrate once daily for hypertension—requires twice-daily dosing for adequate 24-hour control 6
• Do not forget renal dose adjustment for atenolol in CKD patients 3
• Do not overlook sex differences—women may need lower metoprolol doses 1