Is Entresto Safe at GFR 54.4?
Yes, Entresto (sacubitril/valsartan) is safe to use at a GFR of 54.4 mL/min/1.73 m², as this falls within the moderate renal impairment range (GFR 30-60) where no dose adjustment is required and the medication has demonstrated both safety and efficacy.
Dosing and Safety in Moderate Renal Impairment
No dose adjustment is necessary for sacubitril/valsartan when GFR is ≥30 mL/min/1.73 m². 1 The FDA label confirms that patients with mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²) can use standard dosing without modification. 2
- Your patient's GFR of 54.4 mL/min/1.73 m² represents stage 3a chronic kidney disease, which is well above the threshold requiring special consideration. 1
- Recent guidelines specifically state that patients with eGFR ≥30 mL/min should be treated according to general heart failure recommendations without renal-based restrictions. 1
Evidence Supporting Use in This GFR Range
Sacubitril/valsartan has demonstrated renal protective effects in patients with moderate renal dysfunction. 1, 3
- In the PARADIGM-HF and PARAGON-HF trials, sacubitril/valsartan was associated with slower eGFR decline compared to ACE inhibitors or ARBs. 1, 4
- A real-world study showed that the decline of eGFR in the sacubitril/valsartan group was significantly slower than in the control group (p = 0.021) among patients with chronic kidney disease and heart failure. 5
- In patients with acute heart failure and renal dysfunction (eGFR 30-60 mL/min/1.73 m²), sacubitril/valsartan was associated with eGFR improvements of 4.1 mL/min/1.73 m² from baseline. 6
Critical Monitoring Parameters
Monitor serum creatinine and potassium closely, particularly in the first few weeks after initiation. 2
- Expect modest, transient eGFR declines (>15%) in approximately 10-11% of patients during initial titration—this is not associated with adverse outcomes and typically partially recovers. 4
- Accept eGFR declines up to 30% during diuresis, as this often reflects appropriate volume reduction rather than true kidney injury. 7
- Check serum potassium periodically, as hyperkalemia risk increases with declining renal function. 2
- Monitor for symptomatic hypotension, especially if the patient is volume-depleted or on high-dose diuretics. 2
When to Exercise Caution
Temporary discontinuation may be warranted during acute illness that increases acute kidney injury risk. 1
- Consider holding sacubitril/valsartan during serious intercurrent illness (severe dehydration, sepsis, major surgery) that could precipitate acute kidney injury. 1
- If eGFR declines below 30 mL/min/1.73 m² during treatment, continuation is still safe and beneficial based on post-hoc analyses of major trials. 3
- Down-titrate or temporarily interrupt if clinically significant renal function decline occurs (not the expected transient changes). 2
Specific Risks at This GFR Level
Hyperkalemia is the primary concern, occurring in 16.3% of patients with renal dysfunction versus 6.5% without. 6
- Avoid concomitant potassium supplements, potassium-sparing diuretics (unless carefully monitored), and NSAIDs. 7, 2
- Educate patients to avoid potassium-based salt substitutes. 7
- The risk of investigator-reported renal impairment was 6.4% in patients with baseline renal dysfunction versus 2.1% without, but most patients tolerated therapy well. 6
Treatment Benefits Are Preserved
The cardiovascular benefits of sacubitril/valsartan remain consistent regardless of baseline renal function or subsequent eGFR changes. 3, 4
- Treatment benefits on primary outcomes were similar in patients with and without eGFR decline during run-in (HR 0.69 vs 0.80 in PARADIGM-HF, p-interaction = 0.32). 4
- Even among patients whose eGFR declined below 30 mL/min/1.73 m² during follow-up, sacubitril/valsartan maintained lower rates of cardiovascular events compared to RAS inhibitors. 3
- Early eGFR changes should not deter continuation or uptitration of sacubitril/valsartan. 4