What is the recommended use of Amlodipine with an Angiotensin-Converting Enzyme (ACE) inhibitor for patients with hypertension or heart failure?

Amlodipine with ACE Inhibitors for Hypertension and Heart Failure

For patients with hypertension or heart failure, the recommended approach is to use amlodipine with an ACE inhibitor as a step-wise therapy, with amlodipine being added as a third-line agent in heart failure with reduced ejection fraction (HFrEF) when blood pressure remains uncontrolled despite optimal therapy with ACE inhibitors, beta-blockers, and mineralocorticoid receptor antagonists. 1

Hypertension Management Algorithm

First-line Therapy

• ACE inhibitors (or ARBs if ACE inhibitor intolerant) should be the first-line therapy for hypertension, particularly in patients with:
  • Heart failure
  • Post-myocardial infarction
  • Diabetes
  • Chronic kidney disease

When to Add Amlodipine

• Add amlodipine when hypertension persists despite treatment with:
  • ACE inhibitor (or ARB)
  • Beta-blocker
  • Mineralocorticoid receptor antagonist (MRA)
  • Diuretic 1

Dosing Considerations

• Start with low doses of both medications
• For ACE inhibitors, options include:
  • Captopril: Start 6.25 mg three times daily, target 50-100 mg three times daily
  • Enalapril: Start 2.5 mg twice daily, target 10-20 mg twice daily
  • Lisinopril: Start 2.5-5.0 mg once daily, target 30-35 mg once daily 1
• For amlodipine: Start with 2.5-5 mg once daily, titrating as needed

Heart Failure Management

For Heart Failure with Reduced Ejection Fraction (HFrEF)

1. First-line therapy: ACE inhibitor (or ARB if intolerant) + beta-blocker + MRA 1
2. Second-line: Add diuretic if congestion persists
3. Third-line: Add amlodipine if hypertension persists 1

Important Considerations

• Amlodipine is the only calcium channel blocker considered safe in heart failure 2
• Avoid non-dihydropyridine calcium channel blockers (diltiazem, verapamil) in HFrEF as they have negative inotropic effects 1, 2
• Avoid alpha-adrenoceptor antagonists due to risk of fluid retention and worsening heart failure 1

Benefits of Combination Therapy

1. Complementary mechanisms of action:

   • ACE inhibitors block the renin-angiotensin-aldosterone system
   • Amlodipine blocks calcium channels in vascular smooth muscle 2

2. Clinical outcomes:

   • Reduced hospitalizations for heart failure
   • Improved exercise capacity
   • Better blood pressure control 3

3. Reduced side effects:

   • The combination of amlodipine with ACE inhibitors may reduce the incidence of peripheral edema compared to amlodipine monotherapy 4

Monitoring and Follow-up

• Monitor blood chemistry (urea, creatinine, potassium) and blood pressure after initiating therapy and with each dose adjustment 1
• Watch for potential adverse effects:
  • ACE inhibitors: Cough, hypotension, hyperkalemia, worsening renal function
  • Amlodipine: Peripheral edema, headache, dizziness 1, 4

Special Considerations

• In patients with ischemic left ventricular dysfunction, the addition of amlodipine to standard therapy (including ACE inhibitors) has been shown to improve symptoms, exercise capacity, and ventricular function 3
• For patients with renal dysfunction, amlodipine appears to have renoprotective effects comparable to ACE inhibitors 5

Cautions and Contraindications

• Avoid using amlodipine as first-line therapy in heart failure; it should be added only after optimal therapy with ACE inhibitors, beta-blockers, and MRAs 1
• Monitor for hypotension when combining these medications, especially in elderly patients or those with volume depletion
• Be cautious with combination therapy in patients with significant renal dysfunction (creatinine >2.5 mg/dL) 1

By following this evidence-based approach to combining amlodipine with ACE inhibitors, clinicians can optimize blood pressure control and improve outcomes in patients with hypertension and heart failure.