Letters to the Editor
Renal Considerations in Sacubitril/Valsartan Uptitration for Heart Failure Patients ― Reply ―
2025 Volume 89 Issue 8 Pages 1446-
Details
2025 Volume 89 Issue 8 Pages 1446-
We express our sincere gratitude to Drs. Ito and Mori for their thoughtful and insightful comments regarding our article on sacubitril/valsartan uptitration in patients with heart failure, based on data from the REVIEW-HF registry.1,2
We fully agree with their observation that the underrepresentation of patients with advanced renal dysfunction in major clinical trials limits our understanding of optimal management strategies in this high-risk population. As highlighted, approximately 20% of patients in our cohort had an eGFR <30 mL/min/1.73 m2, reflecting a real-world population that is often excluded from randomized controlled trials.3,4
It is well established that the plasma concentration of sacubitril/valsartan correlates with kidney function.5 Moreover, as noted in the JCS/JHFS 2025 Guideline on diagnosis and treatment of heart failure, impaired renal function is associated with elevated natriuretic peptide levels and worse prognosis, highlighting the need for cautious and individualized drug titration in this population.6 Ujiro et al. reported that patients with cardiorenal anemia syndrome (CRAS), a condition characterized by the coexistence of heart failure, renal dysfunction, and anemia, had significantly worse prognoses compared to those without these comorbidities. Their findings underscore the compound risk associated with multiple organ dysfunctions in heart failure patients.7 In addition, it has been suggested that malnourished heart failure patients have a higher prevalence of kidney dysfunction, and that sacubitril/valsartan may be less effective in patients with malnutrition.8 These findings are consistent with our results, indicating that patients with severe kidney dysfunction and malnutrition are less likely to tolerate or reach a high dose of sacubitril/valsartan. Therefore, our study emphasizes the importance of tailored heart failure pharmacotherapy in patients with both kidney dysfunction and malnutrition.
Further targeted research is needed to determine the optimal dosing strategy of sacubitril/valsartan in patients with severe renal dysfunction and poor nutritional status.
K. Kida received honoraria from AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., Nippon. Boehringer Ingelheim Co., Ltd., Bayer Yakuhin Ltd., Otsuka Pharmaceutical Co., Ltd., and Novartis Pharmaceuticals Co., Ltd.
