What is the recommended first-line treatment for hypertension and heart failure using Renin-Angiotensin (RA) blockers, such as Angiotensin-Converting Enzyme (ACE) inhibitors or Angiotensin Receptor Blockers (ARBs)?

First-Line Treatment with Renin-Angiotensin System Blockers for Hypertension and Heart Failure

For patients with heart failure with reduced ejection fraction (HFrEF), an angiotensin receptor-neprilysin inhibitor (ARNI) such as sacubitril-valsartan is recommended as first-line therapy to reduce morbidity and mortality. 1

Treatment Algorithm for Heart Failure with Reduced Ejection Fraction

First-Line Therapy Options (in order of preference):

1. ARNI (Sacubitril-Valsartan)

   • First choice for patients with NYHA class II-III symptoms
   • Initial dose: 49/51 mg twice daily
   • Target dose: 97/103 mg twice daily
   • Contraindicated in patients with history of angioedema
   • Do not administer within 36 hours of ACE inhibitor use 1

2. ACE Inhibitors

   • When ARNI is not feasible
   • Options include:
     • Lisinopril: 2.5-5 mg daily → 20-40 mg daily
     • Enalapril: 2.5 mg twice daily → 10-20 mg twice daily
     • Ramipril: 1.25-2.5 mg daily → 10 mg daily
   • Contraindicated in patients with history of angioedema 1, 2

3. ARBs

   • For patients intolerant to ACE inhibitors (cough, angioedema)
   • Options include:
     • Candesartan: 4-8 mg daily → 32 mg daily
     • Losartan: 25-50 mg daily → 50-100 mg daily
     • Valsartan: 20-40 mg twice daily → 160 mg twice daily 1

Treatment for Hypertension

For patients with hypertension, the recommended first-line treatments include:

1. ACE Inhibitors or ARBs

   • Particularly beneficial in patients with:
     • Diabetes
     • Chronic kidney disease
     • High cardiovascular risk 1

2. Thiazide Diuretics

   • Effective for blood pressure control
   • Consider as first-line therapy or in combination with RAS blockers 1, 3

3. Beta-Blockers

   • Particularly for patients with:
     • Prior myocardial infarction
     • Angina
     • Tachyarrhythmias 1

Important Clinical Considerations

Efficacy Comparisons

• ACE inhibitors have been shown to reduce morbidity and mortality in HFrEF 1
• ARBs are equally effective for blood pressure control but may have slightly less evidence for mortality reduction in heart failure compared to ACE inhibitors 4, 5
• ARNIs are superior to ACE inhibitors in reducing heart failure hospitalizations and cardiovascular mortality in HFrEF 1

Side Effect Profiles

• ACE inhibitors: Cough (5-20%), angioedema (rare), hypotension, hyperkalemia, renal dysfunction 6
• ARBs: Lower incidence of cough, similar rates of hypotension, hyperkalemia, and renal dysfunction 7, 4
• ARNIs: Hypotension, hyperkalemia, renal dysfunction, angioedema (contraindicated if history with ACE inhibitors) 1

Monitoring Requirements

• Check renal function and potassium before initiation and 1-2 weeks after starting therapy or dose changes
• Monitor blood pressure, including postural changes
• Watch for signs of angioedema, particularly with ACE inhibitors and ARNIs 1, 6

Contraindications and Precautions

• Avoid dual RAS blockade (ACE inhibitor + ARB) due to increased risk of hyperkalemia and renal dysfunction 6, 7
• Do not use ARNIs within 36 hours of ACE inhibitor administration 1
• Use caution with NSAIDs as they may reduce efficacy and increase renal dysfunction risk 6, 7
• Avoid in pregnancy (teratogenic)
• Use with caution in bilateral renal artery stenosis

Common Pitfalls to Avoid

1. Underdosing: Many patients receive lower doses than those proven effective in clinical trials. Aim for target doses unless limited by side effects 2

2. Inappropriate discontinuation: Do not stop therapy due to mild, asymptomatic reductions in GFR or mild hyperkalemia

3. Failure to switch from ACE inhibitor to ARNI: Patients with HFrEF who tolerate ACE inhibitors or ARBs should be considered for switching to ARNI for further reduction in morbidity and mortality 1

4. Inadequate monitoring: Failure to check renal function and electrolytes after initiation or dose changes

5. Combining multiple RAS blockers: Avoid combining ACE inhibitors with ARBs or direct renin inhibitors due to increased adverse effects without additional benefit 6, 7