What are the considerations when switching an adult patient with heart failure with reduced ejection fraction (HFrEF) and hypertension from Entresto (sacubitril/valsartan) to valsartan?

Switching from Entresto to Valsartan in HFrEF: Clinical Considerations

Switching from Entresto (sacubitril/valsartan) to valsartan alone in patients with HFrEF represents a significant therapeutic downgrade that will likely increase cardiovascular mortality and heart failure hospitalizations, and should only be considered when compelling contraindications to sacubitril/valsartan emerge. 1

Why This Switch Is Problematic

The evidence strongly favors maintaining sacubitril/valsartan over reverting to valsartan monotherapy:

• Sacubitril/valsartan reduces cardiovascular death and HF hospitalization by 20% compared to ACE inhibitors (and by extension, ARBs like valsartan alone) in patients with chronic HFrEF who remain symptomatic despite optimal medical therapy 1, 2

• The PARADIGM-HF trial demonstrated that sacubitril/valsartan significantly decreased both hospitalizations and mortality compared to enalapril, with similar efficacy expected versus valsartan monotherapy 1

• Multiple cost-effectiveness analyses found sacubitril/valsartan provides high value with costs per QALY <$60,000, making it economically justified despite higher upfront costs 1

Legitimate Reasons to Consider This Switch

Only proceed with switching to valsartan if one of these absolute contraindications develops:

• Angioedema: History of angioedema related to sacubitril/valsartan is an absolute contraindication to continued use 3

• Pregnancy: When pregnancy is detected, discontinue sacubitril/valsartan immediately as drugs acting on the renin-angiotensin system can cause fetal injury and death 3

• Severe hypersensitivity reaction: Any component hypersensitivity that is not manageable 3

• Severe hepatic impairment: Use is not recommended in this population 3

Common Pitfalls That Should NOT Trigger a Switch

Do not switch to valsartan for these reasons, as they can be managed while maintaining sacubitril/valsartan:

• Asymptomatic hypotension: Sacubitril/valsartan maintains efficacy and safety even with systolic BP <110 mmHg; asymptomatic hypotension should not prevent continuation 1, 2, 4

• Symptomatic hypotension: First reduce loop diuretic doses in non-congested patients, or temporarily reduce sacubitril/valsartan dose then re-titrate upward 1, 4

• Mild renal dysfunction: Creatinine elevation <0.5 mg/dL is acceptable and does not require discontinuation; severe renal impairment (eGFR <30) requires dose adjustment to 24/26 mg twice daily, not discontinuation 4, 3

• Hyperkalemia: Monitor potassium levels and adjust concomitant medications (particularly aldosterone antagonists) rather than discontinuing sacubitril/valsartan 1, 3

• Cost concerns: While cost may be a barrier, the mortality benefit and cost-effectiveness data support continued use 1

How to Execute the Switch If Absolutely Necessary

If you must switch from sacubitril/valsartan to valsartan:

• No washout period is required when switching from sacubitril/valsartan to an ARB like valsartan, unlike the mandatory 36-hour washout required when switching from an ACE inhibitor to sacubitril/valsartan 1, 4, 3

• Start valsartan at an appropriate dose for HFrEF (typically 40-80 mg twice daily, titrating to target dose of 160 mg twice daily) 1

• Monitor closely for clinical decompensation, as patients will lose the neprilysin inhibition benefits that reduce natriuretic peptide degradation 1

• Ensure other guideline-directed medical therapies (beta-blockers, mineralocorticoid receptor antagonists, SGLT2 inhibitors) are optimized to partially compensate for the loss of sacubitril/valsartan's mortality benefit 1, 2

Clinical Outcomes to Expect After Switching

Patients switched from sacubitril/valsartan to valsartan will likely experience:

• Loss of the 20% relative risk reduction in cardiovascular death and HF hospitalization that sacubitril/valsartan provides 1, 2

• Potential increases in NT-proBNP levels, as neprilysin inhibition is removed 5, 6

• Possible worsening of cardiac remodeling parameters over time, as sacubitril/valsartan has been shown to improve LVEF and reduce ventricular volumes regardless of HF duration 5, 6

• Potential decline in functional status and quality of life measures 5, 6

Alternative Approach: Reconsider the Need to Switch

Before proceeding with this therapeutic downgrade, exhaust all options to maintain sacubitril/valsartan:

• If hypotension is the concern, reduce to the lowest dose (24/26 mg twice daily) rather than discontinuing entirely 4, 3

• Address volume status and reduce diuretics if the patient is not congested 1, 4

• Provide patient education about asymptomatic hypotension being acceptable and not harmful 1, 2

• For financial barriers, explore patient assistance programs and generic alternatives as they become available 1