What about adding Angiotensin-Converting Enzyme (ACE) inhibitors or Angiotensin Receptor Blockers (ARBs) to a patient's regimen?

Adding ACE Inhibitors or ARBs to a Patient's Regimen

ACE inhibitors or ARBs should be added to a patient's regimen for heart failure with reduced ejection fraction (HFrEF), as they reduce morbidity and mortality, with ACE inhibitors being the first-line choice and ARBs reserved for patients who cannot tolerate ACE inhibitors due to side effects like cough or angioedema. 1

Indications for ACE Inhibitors and ARBs

• ACE inhibitors are the first-choice agents for inhibition of the renin-angiotensin system in chronic heart failure 1
• ARBs are recommended for patients who are ACE inhibitor intolerant (Class I, Level of Evidence A) 1
• Both ACE inhibitors and ARBs reduce hospitalizations and mortality in heart failure patients 1
• These medications are also indicated for hypertension management in patients with chronic coronary disease, especially those with compelling indications such as recent myocardial infarction 1

Dosing and Titration

• Start with low doses and gradually titrate up to target doses (see table below for common starting and maximum doses) 1
• Monitor blood pressure (including postural changes), renal function, and potassium within 1-2 weeks after initiation and after dose changes 1
• For stable patients, consider adding beta-blockers before reaching full target doses of ACE inhibitors or ARBs 1

Common ACE Inhibitor Starting and Maximum Doses:

• Captopril: 6.25 mg three times daily → 50 mg three times daily
• Enalapril: 2.5 mg twice daily → 10-20 mg twice daily
• Lisinopril: 2.5-5 mg once daily → 20-40 mg once daily 1

Common ARB Starting and Maximum Doses:

• Candesartan: 4-8 mg once daily → 32 mg once daily
• Losartan: 25-50 mg once daily → 50-100 mg once daily
• Valsartan: 20-40 mg twice daily → 160 mg twice daily 1

Side Effects and Monitoring

• Monitor for hypotension, especially in patients with systolic BP <80 mmHg, low serum sodium, diabetes, or impaired renal function 1
• Check renal function and potassium levels within 1-2 weeks after initiation and with dose changes 1
• ACE inhibitors may cause cough in some patients (more common) and angioedema (less common but potentially life-threatening) 1
• Angioedema occurs in <1% of patients taking ACE inhibitors but is more frequent in blacks 1
• ARBs have a lower incidence of cough and angioedema compared to ACE inhibitors 2

Special Considerations

• Pregnancy: ACE inhibitors and ARBs are contraindicated during pregnancy due to risk of fetal harm 1
• Renal impairment: Use with caution; monitor renal function closely 3
• Hyperkalemia risk: Increased when combined with potassium-sparing diuretics, aldosterone antagonists, or in patients with renal dysfunction 4
• Drug interactions: Avoid dual blockade of the renin-angiotensin system (combining ACE inhibitor with ARB) as it increases risks of hypotension, hyperkalemia, and renal dysfunction without additional benefits in most patients 4, 5

Algorithm for Adding ACE Inhibitors or ARBs

1. First choice: Start with an ACE inhibitor at a low dose and titrate up as tolerated 1
2. If ACE inhibitor not tolerated due to cough: Switch to an ARB 1, 2
3. If angioedema occurs with ACE inhibitor: Discontinue immediately and avoid all ACE inhibitors; consider ARB with extreme caution as cross-reactivity can occur 1
4. For patients with heart failure: Add an aldosterone antagonist if the patient remains symptomatic on an ACE inhibitor/ARB plus beta-blocker 1
5. For resistant hypertension: Consider adding a mineralocorticoid receptor antagonist to the regimen 1

Common Pitfalls to Avoid

• Dual RAS blockade: Routine combined use of an ACE inhibitor, ARB, and aldosterone antagonist is potentially harmful and not recommended 1, 4
• NSAIDs: Can attenuate the antihypertensive effect of ACE inhibitors/ARBs and increase risk of renal dysfunction 4
• Monitoring failure: Not checking renal function and potassium after initiation or dose changes 1, 3
• Inadequate follow-up: Failing to assess for side effects like hypotension, especially in high-risk patients 1
• Inappropriate discontinuation: Stopping therapy due to mild, asymptomatic increases in creatinine, which are often expected 3