Is Valsartan (Angiotensin Receptor Blocker) part of Guideline-Directed Medical Therapy (GDMT) for Heart Failure (HF)?

Valsartan's Role in Guideline-Directed Medical Therapy for Heart Failure

Yes, valsartan (an Angiotensin Receptor Blocker) is part of Guideline-Directed Medical Therapy (GDMT) for Heart Failure (HF), but primarily as an alternative when ACE inhibitors or sacubitril/valsartan cannot be used. 1

Position of ARBs in Heart Failure Treatment

ARBs like valsartan are positioned in current guidelines as follows:

• For HFrEF (Heart Failure with reduced Ejection Fraction):

  • ARBs are recommended as an alternative for patients who are intolerant to ACE inhibitors or sacubitril/valsartan 1
  • They are not first-line therapy but part of the core HFrEF medications when ACE inhibitors cannot be used

• For HFmrEF (Heart Failure with mildly reduced Ejection Fraction, LVEF 41-49%):

  • ARBs are recommended with a Class 2b recommendation 1
  • Evidence comes from post-hoc analyses such as the CHARM trials, where candesartan reduced risk of cardiovascular death and HF hospitalization in patients with LVEF 41-49% 1

FDA-Approved Indications for Valsartan

According to the FDA label, valsartan is specifically indicated:

• "To reduce the risk of hospitalization for heart failure in adult patients with heart failure (NYHA class II-IV)" 2
• "In clinically stable adult patients with left ventricular failure or left ventricular dysfunction following myocardial infarction, valsartan is indicated to reduce the risk of cardiovascular mortality" 2

Hierarchy of GDMT for Heart Failure

Current 2021-2022 guidelines recommend a core treatment approach for HFrEF that includes:

1. First-line therapies:

   • ACE inhibitors OR sacubitril/valsartan (preferred over ACE inhibitors)
   • Evidence-based beta-blockers
   • Mineralocorticoid receptor antagonists (MRAs)
   • SGLT2 inhibitors

2. ARBs (including valsartan) are positioned as alternatives when:

   • Patients are intolerant to ACE inhibitors or sacubitril/valsartan 1
   • The 2020 European Journal of Heart Failure framework considers ARBs as essential inhibitors of the renin-angiotensin system when other options cannot be used 1

Clinical Evidence for Valsartan

Valsartan has demonstrated efficacy in heart failure:

• The Val-HeFT trial showed valsartan significantly reduced the combined endpoint of mortality and morbidity, with significant reduction in hospitalization risk 3
• Improvements were seen in NYHA functional class, symptoms, quality of life, and left ventricular function 3
• The CHARM trials further confirmed the benefits of ARBs in heart failure 3

Valsartan in Combination Therapy

Valsartan is also a component of sacubitril/valsartan (Entresto), which is now preferred over ACE inhibitors:

• Sacubitril/valsartan has demonstrated superior outcomes compared to enalapril in the PARADIGM-HF trial 4
• Real-world data shows sacubitril/valsartan is associated with symptom improvements and reduction in hospitalizations within 4 months of treatment 5

Common Pitfalls in ARB Use for Heart Failure

• Underutilization: Only about 22-24% of eligible patients receive ARBs according to registry data 1
• Inadequate dosing: Only 49.5% of patients on ARBs receive ≥50% of target doses 1
• Inappropriate discontinuation: High discontinuation rates (33%) have been observed within 12 months 1
• Monitoring failures: Inadequate monitoring of renal function and potassium levels after initiation or dose changes

Practical Considerations

• Monitor renal function and potassium levels 1-2 weeks after initiation and dose changes
• Target doses should be achieved when possible, with gradual up-titration
• Valsartan should be considered in patients who cannot tolerate ACE inhibitors due to cough
• Avoid combining valsartan with ACE inhibitors as there is no evidence of added benefit 2

Valsartan remains an important component of GDMT for heart failure, particularly when first-line options cannot be used due to intolerance or contraindications.