What are the recommended Angiotensin-Converting Enzyme Inhibitors (ACEIs) and Angiotensin Receptor Blockers (ARBs) for patients with comorbidities, particularly those that are widely available?

Recommended ACEIs and ARBs for Comorbidities in the Philippines

For patients with comorbidities, the most accessible and recommended ACEIs in the Philippines are lisinopril, enalapril, and ramipril, while the most accessible ARBs are losartan, valsartan, and candesartan. 1

ACEIs and ARBs for Specific Comorbidities

Heart Failure

• For patients with heart failure with reduced ejection fraction (HFrEF), ACEIs are first-line therapy with recommended options including:

  • Captopril (6.25 mg 3 times daily, max 50 mg 3 times daily) 1
  • Enalapril (2.5 mg twice daily, max 10-20 mg twice daily) 1
  • Lisinopril (2.5-5 mg once daily, max 20-40 mg once daily) 1
  • Ramipril (1.25-2.5 mg once daily, max 10 mg once daily) 1

• If ACEIs are not tolerated (due to cough or angioedema), ARBs can be used:

  • Candesartan (4-8 mg once daily, max 32 mg once daily) 1
  • Valsartan (20-40 mg twice daily, max 160 mg twice daily) 1
  • Losartan (25-50 mg once daily, max 50-100 mg once daily) 1

Chronic Kidney Disease

• For patients with CKD, especially with albuminuria:
  • ACEIs: Benazepril, enalapril, lisinopril, or ramipril 1
  • ARBs: Irbesartan, losartan, or valsartan 1
  • Starting doses should be lower in patients with reduced renal function 1

Diabetes

• For patients with diabetes, especially with albuminuria:
  • ACEIs are preferred first-line agents: Ramipril, enalapril, or lisinopril 1
  • ARBs if ACEIs not tolerated: Losartan, irbesartan, or valsartan 1

Coronary Artery Disease

• ACEIs are recommended for all patients with CAD:
  • Ramipril, perindopril, or trandolapril 1, 2
  • ARBs (valsartan or candesartan) only if ACEIs are not tolerated 1

Post-Stroke

• Recommended options:
  • ACEIs: Perindopril, ramipril, or lisinopril 1, 2
  • ARBs: Candesartan or losartan 1

Atrial Fibrillation

• ARBs may reduce AF recurrence:
  • Losartan or valsartan 1

Dosing and Titration Considerations

Initial Dosing

• Start with low doses, especially in:
  • Elderly patients 1
  • Patients with systolic BP <120 mmHg 1
  • Patients with renal impairment 1, 3
  • Patients on diuretics 3, 4

Titration

• Titrate gradually by doubling doses every 2-4 weeks 1
• Monitor blood pressure, renal function, and potassium within 1-2 weeks after initiation and after each dose increase 1, 3
• Target doses should be the highest tolerated within the recommended range 5, 6

Monitoring and Safety Considerations

Monitoring Parameters

• Blood pressure (including postural changes) 1
• Serum creatinine and eGFR 1, 7
• Serum potassium 1, 7
• Monitor more frequently in high-risk patients (elderly, diabetics, CKD) 1

Common Adverse Effects

• ACEIs: Dry cough (more common), angioedema (rare but serious) 1, 3
• ARBs: Less cough but can still cause angioedema (though less frequently) 1, 4
• Both: Hypotension, hyperkalemia, worsening renal function 1, 7

Important Precautions

• Avoid dual RAS blockade (ACEI + ARB) due to increased risk of hyperkalemia and renal dysfunction 3, 4
• Use caution with NSAIDs as they may reduce efficacy and increase renal risk 3, 4
• Contraindicated in pregnancy 2
• Monitor lithium levels if co-administered 3, 4

Most Accessible Options in the Philippines

Most Accessible ACEIs

1. Enalapril - widely available as generic, once or twice daily dosing 3
2. Lisinopril - once daily dosing, good for adherence 1
3. Ramipril - once daily dosing, evidence for cardiovascular protection 1, 8

Most Accessible ARBs

1. Losartan - widely available as generic, moderate cost 4
2. Valsartan - good evidence in heart failure 1
3. Candesartan - evidence in heart failure with preserved ejection fraction 1

Special Considerations

• For patients unable to tolerate ACEIs due to cough, ARBs are the recommended alternative 1
• Once-daily medications improve adherence compared to multiple daily dosing 1
• Single-pill combinations with other antihypertensives can improve adherence 1
• Higher doses of ACEIs may provide greater benefits in heart failure 5, 6
• ACEIs may have superior protective effects compared to ARBs for post-MI patients 8, 9