What is a better drug for reduced ejection fraction, metoprolol (beta-blocker) or olmesartan (angiotensin II receptor antagonist)?

Metoprolol is Superior to Olmesartan for Reduced Ejection Fraction

For patients with reduced ejection fraction, metoprolol is superior to olmesartan as it significantly reduces all-cause mortality, sudden death, and deaths from worsening heart failure. 1, 2

Evidence Supporting Metoprolol for HFrEF

Mortality Benefits

• Metoprolol CR/XL has been shown to reduce:

  • All-cause mortality by 34%
  • Sudden death by 41%
  • Deaths from worsening heart failure by 49% 3, 1

• The MERIT-HF trial demonstrated that metoprolol significantly reduced all-cause mortality and hospitalizations in both men and women with heart failure and reduced ejection fraction 3

Guideline Recommendations

• Beta-blockers (including metoprolol) are considered essential and broadly applicable to patients with chronic heart failure and reduced ejection fraction 3

• Treatment of patients with heart failure with reduced ejection fraction should include a beta-blocker with proven cardiovascular outcomes benefit (Class I recommendation) 3

• Metoprolol is one of only three beta-blockers (along with bisoprolol and carvedilol) that have demonstrated mortality benefits in HFrEF 3

Olmesartan and HFrEF

• Angiotensin receptor blockers (ARBs) like olmesartan have a more modest benefit on mortality (5-16% risk reduction) compared to beta-blockers 3

• In patients with reduced ejection fraction, the addition of olmesartan to the combination of ACE inhibitor and beta-blocker was actually associated with increased mortality (hazard ratio 2.26) and worsening renal function 4

Dosing and Administration of Metoprolol

• Start with low doses (12.5-25 mg once daily) and gradually titrate to target dose of 200 mg once daily 3, 5
• Titration should occur over several weeks to months, with dose increases every 2 weeks if tolerated 5

Important Considerations

Contraindications for Metoprolol

• Severe bradycardia
• Second or third-degree heart block without pacemaker
• Cardiogenic shock
• Decompensated heart failure requiring IV inotropic therapy
• Severe asthma 5

Potential Challenges

• Genetic variations in CYP2D6 enzymes may affect metoprolol metabolism and dosing requirements, particularly in patients of European and Asian ancestry 6
• If patients cannot tolerate metoprolol titration, consider switching to carvedilol which has a different metabolic pathway 6

Combination Therapy

• Metoprolol should be used as part of comprehensive guideline-directed medical therapy for HFrEF
• Other essential medications include:
  • ACE inhibitors or ARBs
  • Mineralocorticoid receptor antagonists
  • SGLT2 inhibitors (in appropriate patients) 3, 5

Conclusion

While olmesartan may have some benefits in hypertensive patients with preserved ejection fraction when combined with beta-blockers 4, the evidence strongly favors metoprolol for patients with reduced ejection fraction due to its well-established mortality benefits and strong guideline recommendations.