Yes, restart Entresto at a low dose with gradual uptitration
A blood pressure of 114/77 mmHg is acceptable for restarting Entresto, and you should proceed with initiation at the lowest dose (24/26 mg or 49/51 mg twice daily) followed by slow uptitration. This systolic BP is above the critical threshold where severe hypotension becomes a major concern.
Key Decision Points
Blood Pressure Thresholds
- Your patient's BP (114/77 mmHg) is above the concerning range. The 2025 ESC Heart Failure Association guidelines define severe hypotension requiring extreme caution as SBP <80 mmHg 1.
- Patients with SBP ≥100 mmHg can successfully achieve target doses of Entresto. In the TITRATION study, 72.7% of patients with SBP 100-110 mmHg achieved and maintained target doses 2.
- The FDA label for PARADIGM-HF excluded patients with SBP <100 mmHg at screening 3, but real-world evidence shows successful use even below this threshold.
Practical Initiation Strategy
Start with the lowest available dose:
- Begin with 24/26 mg or 49/51 mg twice daily 1
- Asian real-world data demonstrates that even a "tiny dose" of 12/13 mg can be effective and well-tolerated in patients with low BP 4
Uptitration approach:
- Increase dose every 1-2 weeks by small increments 1
- For patients with BP in the 100-120 mmHg range, gradual 6-week uptitration is superior to rapid 3-week uptitration (80% vs 69% treatment success) 2
- Monitor BP closely during each dose adjustment
Critical Assessment Before Restarting
First, determine WHY Entresto was stopped:
- If the patient was stable on Entresto and developed low BP, look for OTHER causes first (volume depletion, other antihypertensives, valvular disease, infection) 1
- Common pitfall: Unnecessarily stopping guideline-directed medical therapy when low BP is actually due to overdiuresis or non-HF medications
Assess volume status:
- Check for signs of congestion (clinical exam, lung ultrasound, elevated natriuretic peptides)
- If euvolemic or overdiuresed, reduce diuretics first 1
- Remove non-essential BP-lowering drugs (calcium channel blockers, alpha-blockers for BPH, centrally-acting antihypertensives) 1
Evaluate symptoms:
- Asymptomatic low BP is generally well-tolerated and should NOT prevent Entresto use 1
- Mild dizziness upon standing can be managed with patient education rather than medication discontinuation 1
- Only severe symptoms (significant orthostatic hypotension, syncope, fatigue preventing daily activities) warrant dose reduction 1
Safety Considerations
Expected adverse effects:
- Hypotension is the most common issue, occurring in ~16% of patients 3, 5
- Risk is higher with lower baseline BP but still manageable 2, 4
- Worsening renal function (
7%) and hyperkalemia (1-5%) are less common 3, 5
Monitoring requirements:
- Check BP, renal function, and potassium within 1-2 weeks of initiation and after each dose increase 1
- Recent case reports suggest monitoring coagulation parameters (PT/INR) may be prudent, though this is a newly recognized potential ADR 6, 7
Contraindications to restart:
- SBP consistently <80 mmHg with symptoms 1
- Severe symptomatic hypotension preventing daily activities
- Acute kidney injury or severe hyperkalemia
The Bottom Line
Your patient with BP 114/77 mmHg should restart Entresto at the lowest dose with gradual uptitration over 6 weeks, provided they are not severely symptomatic and other causes of hypotension have been addressed. The mortality and morbidity benefits of Entresto far outweigh the risk of mild hypotension in this BP range 8, 3. Patient education about transient dizziness being a side effect of life-prolonging therapy improves adherence 1.