Can a 72-year-old woman with biventricular heart failure post‑pericardial window for tamponade be treated with tolvaptan in addition to sacubitril/valsartan (Entresto) and dapagliflozin?

Can Tolvaptan Be Combined with Entresto and Dapagliflozin in Biventricular Heart Failure?

Yes, tolvaptan can be added to Entresto (sacubitril/valsartan) and dapagliflozin in this patient with biventricular heart failure, but only after optimizing standard diuretic therapy and ensuring careful monitoring of volume status, electrolytes, and renal function.

Guideline-Directed Medical Therapy Foundation

Your patient should be on quadruple therapy for HFrEF as the foundation 1:

• Entresto (sacubitril/valsartan): Target dose 97/103 mg twice daily 1
• Dapagliflozin: 10 mg once daily 1
• Beta-blocker: Titrated to target dose 1
• Mineralocorticoid receptor antagonist (MRA): Spironolactone 25-50 mg daily or eplerenone 50 mg daily 1

Evidence for Combining These Agents

The combination of Entresto and dapagliflozin is safe and effective. In the DAPA-HF trial, dapagliflozin demonstrated similar efficacy and safety in patients taking sacubitril/valsartan (HR 0.75,95% CI 0.50-1.13) compared to those not taking it (HR 0.74,95% CI 0.65-0.86) 2. Real-world data shows that combined sacubitril/valsartan plus dapagliflozin therapy produces greater reductions in NT-proBNP and left atrial diameter compared to sacubitril/valsartan monotherapy 3.

Role of Tolvaptan in This Context

Tolvaptan is not part of guideline-directed medical therapy for chronic heart failure management 1. The 2022 ACC/AHA/HFSA guidelines do not include vasopressin antagonists like tolvaptan in the standard treatment algorithm for HFrEF 1.

When to Consider Tolvaptan

Tolvaptan may be considered in specific scenarios:

• Refractory volume overload despite maximized loop diuretics (furosemide ≥160 mg/day or equivalent) 1
• Hyponatremia (serum sodium <130 mEq/L) complicating heart failure management 1
• Diuretic resistance requiring escalating doses with inadequate response 1
• Worsening renal function limiting ability to increase loop diuretics 1

Critical Safety Considerations

Before adding tolvaptan to Entresto and dapagliflozin, ensure:

1. Volume status assessment: Patient must have evidence of persistent congestion despite optimized loop diuretics 1
2. Electrolyte monitoring: Check sodium, potassium, and renal function at baseline and within 24-48 hours of initiation 1
3. Blood pressure monitoring: All three agents can lower blood pressure; ensure systolic BP >100 mmHg before adding tolvaptan 1, 4
4. Renal function: Monitor creatinine and eGFR closely, as the combination may affect renal perfusion 1, 4

Practical Algorithm for This Patient

Step 1: Optimize Standard Diuretic Therapy First

• Maximize loop diuretic dose (furosemide up to 160-240 mg/day in divided doses) 1
• Consider adding thiazide diuretic for sequential nephron blockade if inadequate response 1
• Ensure MRA is at target dose (spironolactone 25-50 mg daily) 1

Step 2: Assess for Tolvaptan Indications

• Document persistent congestion (orthopnea, paroxysmal nocturnal dyspnea, elevated jugular venous pressure, peripheral edema) 1
• Check serum sodium; if <130 mEq/L, tolvaptan has stronger indication 1
• Verify diuretic resistance (inadequate urine output or weight loss despite high-dose loop diuretics) 1

Step 3: If Adding Tolvaptan

• Starting dose: 15 mg once daily 1
• Titration: May increase to 30 mg daily after at least 24 hours if needed 1
• Monitoring: Check sodium, potassium, creatinine within 24-48 hours, then every 2-3 days initially 1
• Diuretic adjustment: Reduce loop diuretic dose by 25-50% when initiating tolvaptan to avoid excessive diuresis 1

Step 4: Monitor for Adverse Effects

• Hypotension: Entresto, dapagliflozin, and tolvaptan all lower blood pressure; monitor closely 1, 4, 2
• Hypernatremia: Tolvaptan can cause rapid sodium correction; avoid increase >8-10 mEq/L in 24 hours 1
• Worsening renal function: The combination may reduce renal perfusion; acceptable creatinine increase is <0.3 mg/dL 1, 4
• Hypovolemia: Watch for orthostatic symptoms, dizziness, or excessive thirst 2

Common Pitfalls to Avoid

• Do not add tolvaptan before maximizing standard diuretics (loop diuretics ± thiazides) 1
• Do not use tolvaptan as first-line therapy for volume management in heart failure 1
• Avoid rapid sodium correction (>8-10 mEq/L in 24 hours) which can cause osmotic demyelination 1
• Do not discontinue MRA when adding tolvaptan; spironolactone/eplerenone are Class 1 recommendations 1
• Monitor potassium carefully when combining MRA with Entresto and dapagliflozin; hyperkalemia risk is increased 1, 4

Special Consideration: Post-Pericardial Window Status

Given this patient's recent pericardial window for tamponade:

• Ensure hemodynamic stability before initiating or uptitrating any of these medications 1
• Monitor for recurrent pericardial effusion, as volume shifts may affect pericardial fluid dynamics 1
• Consider echocardiographic reassessment if clinical status changes after medication adjustments 1

Bottom Line

Tolvaptan can be safely combined with Entresto and dapagliflozin, but should be reserved for refractory congestion or hyponatremia after optimizing standard diuretic therapy. The combination of Entresto and dapagliflozin is evidence-based and strongly recommended 1, 2, 3. Tolvaptan serves as an adjunctive agent for specific indications, not routine use 1. Close monitoring of blood pressure, electrolytes, and renal function is essential when using all three agents together 1, 4, 2.