Sacubitril/valsartan exhibits CV and kidney protective benefits across the spectrum of kidney risk in heart failure patients: JACC

Patients with heart failure often experience renal dysfunction, complicating their treatment and prognosis. Sacubitril/valsartan, a combination angiotensin receptor-neprilysin inhibitor (ARNI), has emerged as a promising therapy for heart failure with reduced ejection fraction (HFrEF), but its effects on patients with renal impairment have been less understood until now.

The study, published in the renowned medical journal Journal of the American College of Cardiology, classified one in four patients with HFrEF as at least high Kidney Disease Improving Global Outcomes (KDIGO) kidney risk; these individuals faced concordantly the highest risks of cardiovascular (CV) events.

"Sacubitril/valsartan exhibited consistent kidney and CV protective benefits and safety across the spectrum of baseline kidney risk," the researchers wrote. "These data further support sacubitril/valsartan initiation in HFrEF across a broad range of kidney risks."

The KDIGO classification integrates both estimated glomerular filtration rate (eGFR) and urine-albumin-creatinine-ratio (UACR) to stratify risk more comprehensively in chronic kidney disease patients. Data assessing whether this classification system is associated with treatment response and prognosis in heart failure populations is limited.

PARADIGM-HF was a global randomized controlled trial (RCT) evaluating sacubitril/valsartan versus enalapril in HFrEF patients. Patients were categorized according to low, moderate, and high/very high KDIGO risk.

Treatment responses were evaluated as per the baseline KDIGO risk. The study's primary outcome was a composite of HF hospitalization or CV death. A renal composite outcome was defined as end-stage kidney disease or a sustained decline in eGFR by ≥40%.

The study led to the following findings:

• Among 1,910 (23%) participants with available data, 42%, 32%, and 26% were classified as low, moderate, and high/very high KDIGO risk, respectively.
• Patients in the highest KDIGO risk categories experienced the highest rates of the primary composite outcome (7.6, 9.4, 14.9 per 100py).
• Sacubitril/valsartan had a similar safety profile and similarly reduced the risk of both the primary outcome and the renal composite outcome across the spectrum of KDIGO risk.

In conclusion, the study demonstrates the safety and efficacy of sacubitril/valsartan across the spectrum of renal impairment in patients with heart failure. These findings provide valuable insights for clinicians and underscore the importance of personalized treatment strategies in optimizing outcomes for patients with heart failure and renal dysfunction.

Reference:

Chatur, S., Neuen, B. L., Claggett, B. L., Beldhuis, I. E., Mc Causland, F. R., Desai, A. S., Rouleau, J. L., Zile, M. R., Lefkowitz, M. P., Packer, M., McMurray, J. J., Solomon, S. D., & Vaduganathan, M. (2024). Effects of Sacubitril/Valsartan Across the Spectrum of Renal Impairment in Patients With Heart Failure. Journal of the American College of Cardiology. https://doi.org/10.1016/j.jacc.2024.03.392