When to use Angiotensin Receptor Blockers (ARBs)?

When to Use Angiotensin Receptor Blockers (ARBs)

ARBs are recommended as first-line therapy in patients who are ACE inhibitor intolerant and have heart failure with reduced ejection fraction (HFrEF), myocardial infarction with left ventricular ejection fraction ≤40%, or hypertension. 1

Primary Indications for ARB Use

1. ACE Inhibitor Intolerance

• First-line alternative when ACE inhibitor causes:
  • Cough (occurs in up to 20% of patients on ACE inhibitors) 1
  • Angioedema (occurs in <1% of patients, more frequently in blacks and women) 1
• ARBs do not inhibit kininase and therefore have much lower incidence of these side effects 1

2. Cardiovascular Conditions

• Heart failure with reduced ejection fraction (HFrEF) 1
  • For patients with current or prior symptoms of HFrEF who cannot tolerate ACE inhibitors
  • Class I recommendation with Level of Evidence A
• Post-myocardial infarction 1
  • In patients with LVEF ≤40% who are ACE inhibitor intolerant
  • Class I recommendation with Level of Evidence A

3. Hypertension Management

• Treatment of hypertension 2
  • To lower blood pressure and reduce risk of fatal and nonfatal cardiovascular events
  • Starting dose typically 40 mg once daily (for telmisartan), range 40-80 mg once daily
• Hypertension with comorbidities 1, 3
  • Particularly beneficial in patients with diabetes, chronic kidney disease, or proteinuria
  • Nephroprotective properties make them preferred agents in these populations

Specific Clinical Scenarios for ARB Use

Heart Failure Management

1. First-line alternative to ACE inhibitors in patients with HFrEF 1

   • For patients with LVEF ≤40% who cannot tolerate ACE inhibitors
   • Should be used in conjunction with evidence-based beta-blockers

2. Reasonable alternative as first-line therapy 1

   • For patients with mild to moderate HF and reduced LVEF
   • Especially for patients already taking ARBs for other indications

Renal Protection

1. Diabetic nephropathy 3, 4

   • ARBs have demonstrated renoprotective effects in patients with type 2 diabetes
   • Reduce proteinuria and slow progression of nephropathy

2. Chronic kidney disease with hypertension 3

   • Regular monitoring of serum creatinine, eGFR, and potassium levels is necessary

Dosing and Monitoring

1. Initiation

   • Start at low doses and titrate upward 1
   • Can be administered with or without food (except valsartan, which shows reduced bioavailability with food) 2, 5

2. Monitoring

   • Assess blood pressure, renal function, and potassium within 1-2 weeks after initiation 1
   • Close monitoring needed for patients with:
     • Systolic blood pressure <80 mm Hg
     • Low serum sodium
     • Diabetes mellitus
     • Impaired renal function

Combination Therapy

1. ARBs with diuretics or calcium channel blockers 6

   • Very effective combinations for hypertension management
   • Several fixed-dose combinations available

2. ARBs with ACE inhibitors 1

   • May be considered in persistently symptomatic patients with HFrEF already on ACE inhibitor and beta-blocker
   • Class IIb recommendation (Level of Evidence A)
   • CAUTION: Routine combined use of ACE inhibitor, ARB, and aldosterone antagonist is potentially harmful (Class III: Harm) 1

Contraindications and Precautions

1. Absolute contraindications

   • Known hypersensitivity to ARBs 2
   • Pregnancy (can cause fetal injury and death) 2
   • Co-administration with aliskiren in diabetic patients 2

2. Use with caution in:

   • Patients with low systemic blood pressure 1
   • Renal insufficiency 1
   • Elevated serum potassium (>5.0 mEq/L) 1
   • Bilateral renal artery stenosis 3

Common Pitfalls and Caveats

1. Cross-reactivity with ACE inhibitors

   • Some patients who developed angioedema with ACE inhibitors may also develop it with ARBs 1
   • Use caution when substituting ARB for ACE inhibitor in patients with history of angioedema

2. Monitoring for adverse effects

   • Most common adverse events include headache, upper respiratory infection, back pain, dizziness 2, 6
   • Risk of hypotension, renal dysfunction, and hyperkalemia increases when combined with other RAAS inhibitors 1

3. NSAIDs interaction

   • Increased risk of renal impairment and reduced antihypertensive effect 2
   • Avoid concomitant use when possible or monitor renal function closely

ARBs represent an effective and well-tolerated class of medications with proven benefits in cardiovascular and renal outcomes. Their role as alternatives to ACE inhibitors is well-established, and in certain populations, they may be considered as first-line agents.