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Effects of Sacubitril/Valsartan on Renal Function in Adults With Heart Failure: A Systematic Review and Meta-Analysis
Joshuan J Barboza1, Darwin A León-Figueroa2, Vinay Pasupuleti3
1Unidad de Revisiones Sistemáticas y Meta-analisis (URSIGET), Vicerrectorado de Investigación, Universidad San Ignacio de Loyola, Lima, Peru.
Insights
Sacubitril/valsartan (S/V) likely reduces doubling serum creatinine in heart failure (HF) patients compared to ACE inhibitors or ARBs. However, S/V may not significantly impact worsening renal function, eGFR decline, or hyperkalemia.
Area of Science:
- Cardiology
- Nephrology
- Pharmacology
Background:
- Heart failure (HF) management often involves medications like angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB).
- Evaluating novel therapeutic options such as sacubitril/valsartan (S/V) for renal protection in HF patients is crucial.
Purpose of the Study:
- To systematically evaluate the effects of sacubitril/valsartan (S/V) on renal outcomes in patients with acute or chronic heart failure (HF).
- To compare S/V against standard ACEI or ARB treatments regarding specific renal function markers.
Main Methods:
- A meta-analysis of randomized controlled trials (RCTs) comparing S/V with ACEI or ARB in adult HF patients was conducted.
- Primary outcome: doubling of serum creatinine (sCr). Secondary outcomes included worsening renal function (WDRF), >50% decline in estimated glomerular filtration rate (eGFR), and hyperkalemia.
- GRADE approach was utilized to assess the certainty of evidence for all outcomes.
Main Results:
- Eight RCTs (n=15,859) were analyzed, encompassing both chronic and acute HF populations.
- Sacubitril/valsartan (S/V) likely reduced doubling of sCr compared to ACEI or ARB (RR 0.77; 95% CI 0.72 to 0.83) with moderate certainty.
- S/V showed little to no difference in WDRF (RR 0.88; low certainty), >50% eGFR decline (RR 0.65; very low certainty), and hyperkalemia (RR 1.01; very low certainty).
Conclusions:
- Sacubitril/valsartan (S/V) demonstrates a probable benefit in reducing serum creatinine doubling in heart failure patients compared to ACEI/ARB.
- The evidence suggests S/V has minimal impact on worsening renal function, significant eGFR decline, and hyperkalemia, though certainty is low to very low.
Background:
We systematically evaluated sacubitril/valsartan (S/V) effects on the renal outcomes of patients with acute or chronic heart failure (HF) receiving angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB).
Method:
Five (5) databases were searched for randomised controlled trials (RCTs) comparing S/V vs ACEI or ARB in adult patients with HF until 2 September 2023. Doubling of the serum creatinine (sCr) level was the primary outcome. Worsening or decline in renal function (WDRF), >50% decline of estimated glomerular filtration rate (eGFR), and hyperkalaemia (serum K+ >5.5 mmol/L) were secondary outcomes. Inverse variance random-effects meta-analyses were performed, and the effects of S/V on outcomes were described using relative risks (RRs) and their 95% confidence intervals (CIs). Subgroup analyses were performed according to the type of HF (chronic vs acute) and left ventricular ejection fraction (<40% vs >40 %). The GRADE approach was used to rate the certainty of evidence (CoE).
Results:
Eight (8) RCTs (n=15,859) were included: four on chronic HF and four on acute HF. Median (interquartile range [IQR]) age was 68.4 (63.8-72.7) years in chronic, and 62 (57.1-70.9) years in acute patients, and 34.1% were female. The median (IQR) follow-up was 29.5 (12-108) weeks in chronic and 22 (8-54) weeks in acute patients. In comparison to ACEI or ARB, S/V likely reduced doubling sCr (RR 0.77; 95% CI 0.72 to 0.83; moderate CoE), may have resulted in little to no difference of WDRF (RR 0.88; 95% CI 0.72 to 1.08; low CoE), and had little to no effect on both >50% decline of eGFR (RR 0.65; 95% CI 0.37 to 1.17; very low CoE) and hyperkalaemia (RR 1.01; 95% CI 0.81 to 1.25; very low CoE) but the evidence was very uncertain.
Conclusions:
In adults with HF, S/V likely reduced doubling sCr compared to ACEI or ARB but may have little to no effect on WDRF, a >50% decline in eGFR, and hyperkalaemia.
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