Do you hold Entresto (sacubitril/valsartan) during an acute heart failure exacerbation with hypotension or impaired renal function?

Entresto Management During Acute Heart Failure Exacerbation

Continue Entresto during acute heart failure exacerbations unless the patient develops cardiogenic shock, severe symptomatic hypotension unresponsive to volume optimization, or true contraindications—temporary dose reduction may be considered for marked volume overload or marginal low cardiac output, but permanent discontinuation is rarely required. 1

Evidence-Based Rationale for Continuation

The 2022 AHA/ACC/HFSA guidelines provide the strongest and most recent evidence that oral guideline-directed medical therapy (GDMT), including ARNI therapy, should be continued during hospitalization for acute decompensated heart failure unless true contraindications exist. 1

Key Supporting Data:

• Discontinuation of RAAS inhibitors (ACEi-ARB) during hospitalization was associated with higher rates of post-discharge mortality and readmission in the GWTG-HF registry 1
• Continuation of neurohormonal blockade during acute exacerbations reduces 30-day mortality and heart failure rehospitalization 1
• The PIONEER-HF trial specifically demonstrated that ARNI (sacubitril/valsartan) use in hospitalized patients with acute decompensated HF reduced NT-proBNP levels without increased rates of adverse events (worsening renal function, hyperkalemia, symptomatic hypotension, angioedema) compared to enalapril 1

When to Temporarily Reduce or Hold Entresto

Hypotension Management Algorithm:

Mild hypotension (SBP 90-110 mmHg) without symptoms:

• Continue Entresto at current dose 1, 2
• Optimize volume status and reduce other vasodilators (nitrates, calcium channel blockers) first 1
• Do not withhold GDMT for mild or transient reductions in blood pressure 1

Symptomatic hypotension with dizziness/lightheadedness:

• First: Correct volume or salt depletion, adjust diuretics and other antihypertensive medications 2
• Second: If hypotension persists despite these measures, reduce Entresto dose temporarily 2
• Permanent discontinuation is usually not required 2

Severe symptomatic hypotension (SBP <90 mmHg) or cardiogenic shock:

• Hold Entresto temporarily until hemodynamic stability is restored 1, 2
• Resume at lower dose once patient stabilizes 2

Renal Function Considerations:

Mild worsening renal function (creatinine increase <50% or eGFR decrease <20%):

• Continue Entresto—small to moderate worsening of renal function does not constitute true acute kidney injury and should not prompt discontinuation 1
• Monitor serum creatinine closely 2

Significant renal dysfunction (creatinine >221 μmol/L [>2.5 mg/dL] or eGFR <30 mL/min/1.73 m²):

• Down-titrate or temporarily interrupt Entresto if clinically significant decrease in renal function occurs 2
• Closely monitor serum creatinine and consider resuming at lower dose when stable 2

Oliguria or progressive azotemia:

• Temporarily hold Entresto until renal function stabilizes 2

Hyperkalemia Management:

Potassium 5.5-6.0 mEq/L:

• Continue Entresto with close monitoring 2
• Optimize diuretics and consider potassium binders 2

Potassium >6.0 mEq/L:

• Dosage reduction or interruption of Entresto may be required 2
• Treat hyperkalemia aggressively and resume at lower dose when potassium normalizes 2

Critical Pitfalls to Avoid

Common Mistake #1: Holding Entresto for Asymptomatic Hypotension

The evidence is clear that asymptomatic low blood pressure should not prompt discontinuation. 1 Patients with HF and lower SBP on sacubitril-valsartan had the same tolerance and relative benefit compared to patients with higher SBP in PARADIGM-HF. 1

Common Mistake #2: Discontinuing for Mild Renal Function Changes

Mild worsening renal function (≤20% decrease in eGFR) is not associated with acute kidney injury and does not offset the beneficial effects of RAAS inhibition. 1 The FDA label specifically states to "closely monitor serum creatinine and down-titrate or interrupt" only for clinically significant decreases in renal function. 2

Common Mistake #3: Permanent Discontinuation Instead of Dose Reduction

Permanent discontinuation of therapy is usually not required—the FDA label and guidelines emphasize temporary dose reduction or interruption with resumption once the precipitating factor is addressed. 2, 1

Monitoring During Acute Exacerbation

• Check renal function and electrolytes at admission and every 1-2 days during acute phase 2
• Monitor blood pressure closely, but do not overreact to asymptomatic readings 1
• Assess volume status daily—marked volume overload may warrant temporary dose reduction 1
• Recheck labs 1-2 weeks after any dose adjustment 2

Initiation During Hospitalization

For patients not previously on Entresto, the PIONEER-HF trial supports initiation during hospitalization for acute decompensated HF once hemodynamically stable, as this approach reduced NT-proBNP without increased adverse events compared to enalapril. 1 Start at lower dose (24/26 mg twice daily) and uptitrate after discharge. 2