Are Jardiance (empagliflozin) and Entresto (sacubitril/valsartan) the same medication for treating heart failure with a severe reduced ejection fraction?

No, Jardiance and Entresto Are Not the Same—They Are Distinct Medications That Work Through Different Mechanisms and Should Both Be Used Together in Heart Failure with Severely Reduced Ejection Fraction

For a patient with heart failure and an ejection fraction of 20%, both Jardiance (empagliflozin) and Entresto (sacubitril/valsartan) should be prescribed as part of comprehensive guideline-directed medical therapy (GDMT), as they represent two of the four foundational medication classes proven to reduce mortality and hospitalization in HFrEF. 1

What Each Medication Does

Entresto (Sacubitril/Valsartan)

• Mechanism: Combines neprilysin inhibition (preventing breakdown of beneficial natriuretic peptides) with angiotensin II receptor blockade
• FDA Indication: Specifically approved to reduce cardiovascular death and hospitalization in chronic heart failure patients with reduced ejection fraction 2
• Evidence: Recommended as a replacement for ACE inhibitors in patients who remain symptomatic despite optimal therapy with ACE-I, beta-blocker, and MRA 3
• Dosing: Target dose is 97/103 mg twice daily, starting at 49/51 mg twice daily 2

Jardiance (Empagliflozin)

• Mechanism: SGLT2 inhibitor that works through multiple pathways including improved myocardial energetics, reduced sodium retention, anti-inflammatory effects, and reverse cardiac remodeling 4
• FDA Indication: Approved to reduce cardiovascular death and hospitalization for heart failure in adults with heart failure 5
• Evidence: Now part of the four-pillar GDMT for HFrEF alongside ARNI/ACE-I/ARB, beta-blockers, and MRAs 1
• Dosing: 10 mg daily (can increase to 25 mg) 4

Why Both Are Essential for Your Patient

The 2022 AHA/ACC/HFSA guidelines explicitly state that GDMT for HFrEF now includes FOUR medication classes: 1

1. SGLT2 inhibitors (Jardiance/empagliflozin)
2. ARNI (Entresto/sacubitril-valsartan) OR ACE-I/ARB
3. Beta-blockers (carvedilol, metoprolol succinate, or bisoprolol)
4. Mineralocorticoid receptor antagonists (spironolactone or eplerenone)

With an EF of 20%, your patient has severe HFrEF and qualifies for all four medication classes based on Class 1 recommendations.

The Complementary Benefits

These medications work synergistically through different pathways:

• Entresto primarily affects neurohormonal activation through the renin-angiotensin-aldosterone system and natriuretic peptide pathways
• Jardiance works through metabolic, hemodynamic, and anti-inflammatory mechanisms independent of the RAAS

Recent research demonstrates that combination therapy with both agents produces superior outcomes compared to either alone:

• Greater improvements in cardiac function (LVEF, ventricular dimensions) 6, 7
• More pronounced reductions in NT-proBNP levels 6, 7
• Lower rates of major adverse cardiac events (MACE) and rehospitalization 7
• Enhanced antioxidant, anti-inflammatory, and anti-apoptotic effects 8

Practical Implementation Algorithm

For your patient with EF 20%:

1. Start or optimize Entresto first (if not already on it):

   • Begin at 24/26 mg or 49/51 mg twice daily
   • Titrate every 2-4 weeks to target dose of 97/103 mg twice daily 2
   • Must wait 36 hours after stopping ACE inhibitor before starting Entresto (angioedema risk)

2. Add Jardiance concurrently or shortly after:

   • Start at 10 mg once daily 5
   • Can be initiated regardless of diabetes status
   • Monitor for volume depletion, especially if on high-dose diuretics

3. Ensure beta-blocker and MRA are also optimized to complete the four-pillar GDMT 1

Critical Safety Considerations

Entresto-specific:

• Contraindicated with ACE inhibitors (must have 36-hour washout) 2
• Monitor for hypotension, hyperkalemia, and renal function 2
• Avoid in pregnancy (fetal toxicity) 2

Jardiance-specific:

• Monitor for ketoacidosis (even with normal glucose), genital mycotic infections, and volume depletion 5
• Reduce dose in severe renal impairment (eGFR <30)
• Temporarily hold during acute illness with reduced oral intake

When using both together:

• Increased hypotension risk—separate dosing times if symptomatic hypotension occurs 6
• Enhanced diuretic effect—may need to reduce loop diuretic dose
• Monitor renal function and potassium more frequently initially

Common Pitfall to Avoid

Do not think of these as interchangeable alternatives. The most common error is prescribing one instead of the other, when current evidence and guidelines mandate using both simultaneously as part of comprehensive GDMT. With an EF of 20%, your patient has the most to gain from complete four-pillar therapy, with both medications providing independent mortality and morbidity benefits 1, 7, 9.