What is the difference between Lisinopril and Metoprolol for treating hypertension or heart failure?

Lisinopril vs. Metoprolol for Hypertension and Heart Failure

Lisinopril (ACE inhibitor) and metoprolol (beta-blocker) serve complementary rather than competing roles in treating hypertension and heart failure, with both medications having strong evidence supporting their use in different clinical scenarios.

Mechanism of Action

• Lisinopril: ACE inhibitor that blocks the conversion of angiotensin I to angiotensin II, reducing vasoconstriction and aldosterone secretion
• Metoprolol: Selective beta-1 blocker that reduces heart rate, cardiac contractility, and blood pressure by blocking beta-adrenergic receptors

Efficacy in Hypertension

• Lisinopril:

  • First-line agent for hypertension
  • Target dose: 20-40 mg once daily 1
  • Particularly beneficial in patients with:
    • Diabetes
    • Proteinuria
    • Left ventricular hypertrophy

• Metoprolol:

  • Effective for hypertension control
  • Target dose: 200 mg once daily (metoprolol succinate) 1
  • Particularly beneficial in patients with:
    • Coronary artery disease
    • Tachyarrhythmias
    • Post-myocardial infarction

Efficacy in Heart Failure

• Lisinopril:

  • Reduces mortality and hospitalizations in heart failure with reduced ejection fraction (HFrEF)
  • Demonstrated 8% lower risk of all-cause mortality at higher doses (32.5-35 mg daily) compared to lower doses in the ATLAS trial 2
  • Recommended for all patients with HFrEF (LVEF ≤40%) 1, 3

• Metoprolol:

  • Specifically metoprolol succinate (CR/XL) reduces mortality by 34% in HFrEF 3, 4
  • Target dose: 200 mg once daily 1
  • Must be initiated at low dose (12.5-25 mg) and gradually titrated 3
  • Contraindicated in acute decompensated heart failure 1

Side Effects and Contraindications

• Lisinopril:

  • Common: Dry cough, dizziness, headache
  • Serious: Angioedema, hyperkalemia, acute kidney injury
  • Contraindicated in pregnancy, bilateral renal artery stenosis, history of angioedema

• Metoprolol:

  • Common: Fatigue, dizziness, bradycardia
  • Serious: Bronchospasm, heart block, hypotension
  • Contraindicated in severe bradycardia, heart block, cardiogenic shock, severe bronchospastic disease 3

Comparative Outcomes

In a retrospective study comparing valsartan (ARB), lisinopril (ACE inhibitor), and metoprolol succinate (beta-blocker), valsartan was associated with a significantly lower risk of cardiovascular or renal events compared to metoprolol (HR 0.70) and a nominally lower risk compared to lisinopril, though the latter was not statistically significant 5.

Clinical Decision Algorithm

1. For Hypertension:

   • First-line: Either medication can be used based on comorbidities
   • With diabetes/kidney disease: Prefer lisinopril
   • With coronary artery disease/tachycardia: Prefer metoprolol
   • For resistant hypertension: Consider combination therapy

2. For Heart Failure with Reduced EF (≤40%):

   • First step: Start ACE inhibitor (lisinopril) at low dose
   • Second step: Add beta-blocker (metoprolol succinate) when patient is stable
   • Third step: Add mineralocorticoid receptor antagonist
   • Fourth step: Add SGLT2 inhibitor
   • Target doses: Lisinopril 20-40 mg daily; Metoprolol succinate 200 mg daily 1, 3

Important Clinical Pearls

• Beta-blockers like metoprolol should be initiated at low doses and gradually titrated up in heart failure patients 1, 3
• Never abruptly discontinue beta-blockers due to risk of rebound ischemia and arrhythmias 1
• Monitor renal function and potassium when using lisinopril, especially in combination with other medications affecting the RAAS system 1
• In acute heart failure, metoprolol should be used cautiously, while lisinopril dose may need to be reduced temporarily 1

Conclusion

Both medications have important roles in cardiovascular disease management. The choice between them depends on specific patient factors, comorbidities, and whether they are being used for hypertension alone or heart failure. In many cases, particularly for heart failure with reduced ejection fraction, both medications are used together as part of guideline-directed medical therapy.