Sacubitril/valsartan, initial dip in estimated glomerular filtration rate, and clinical outcomes in patients with heart failure
M Manabe, T Nasu, S Ishii, N Kagiyama, K Kida, W Fujimoto, A Kikuchi, T Ijichi, T Shibata, T Ikeda, K Kanaoka, S MatsumotoAbstract
Background
An early decline in estimated glomerular filtration rate (eGFR) is known to occur after initiation of sacubitril/valsartan, which generally reflect its pharmacological effect and is not linked to worse heart failure (HF) outcomes. However, its incidence and prognostic implications remain unclear in real-world practice.
Purpose
To investigate the association between an initial dip in eGFR and subsequent clinical outcomes in real-world HF patients treated with sacubitril/valsartan.
Methods
We analyzed data from a Japanese nationwide, multicenter, retrospective study (REVIEW-HF), which enrolled those with HF newly prescribed sacubitril/valsartan. We examined the association between an "initial dip" in eGFR (≥15% decline at 2 weeks) and subsequent cardiovascular death.
Results
Among 747 patients with available eGFR measurements at baseline and 2 weeks, an initial dip occurred in 158 (21.2%). In a landmark analysis from 2 weeks, patient experiencing an initial eGFR decline had a higher subsequent risk of cardiovascular death compared to those without, even after adjustment (adjusted hazard ratio: 2.73, 95% confidence interval: 1.33–5.62, P<0.01) (Figure). Decline in eGFR as a continuous variable was also associated with worse outcomes (Figure).
Conclusion
An "Initial dip" in eGFR was not uncommon after sacubitril/valsartan initiation, and its incidence was associated with worse outcomes, suggesting an early eGFR decline may not simply reflect a pharmacological effect but often reflect underlying disease progression in real-world settings.Association between eGFR decline and CVFor image description, please refer to the figure legend and surrounding text.