Chatur, S. et al. (2024) Sacubitril/valsartan in patients with heart failure and deterioration in eGFR to <30 mL/min/1.73 m2. JACC: Heart Failure, (doi: 10.1016/j.jchf.2024.03.014) (PMID:38842957) (In Press)
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Abstract
Background Sacubitril/valsartan is a foundational therapy for patients with heart failure. Although current U.S. Food and Drug Administration labeling does not provide guidance regarding initiation or continuation of sacubitril/valsartan in patients with worsening kidney function, guidelines identify estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 as a contraindication to therapy. Objectives This study aims to assess the safety and efficacy of continuing sacubitril/valsartan in patients with deterioration of kidney function below an eGFR of 30 mL/min/1.73 m2. Methods The association between a deterioration in eGFR <30 mL/min/1.73 m2, efficacy and safety outcomes, and treatment with sacubitril/valsartan vs renin-angiotensin system inhibitor were evaluated using time updated Cox models in a post hoc parallel trial analyses of PARADIGM-HF and PARAGON-HF. Results Among 8,346 randomized patients in PARADIGM-HF and 4,746 in PARAGON-HF, 691 (8.3%) and 613 (12.9%), respectively, had an eGFR <30 mL/min/1.73 m2 at least once in follow-up. Patients experiencing such deterioration were at higher risk of the primary outcome in both PARADIGM-HF and PARAGON-HF. However, the incidence of the primary outcome remained lower with sacubitril/valsartan vs renin-angiotensin system inhibitor, regardless of deterioration in kidney function in both PARADIGM-HF (Pinteraction = 0.50) and PARAGON-HF (Pinteraction = 0.64). Rates of key safety outcomes were higher among patients experiencing eGFR deterioration; however, rates were similar between treatment groups including among those who remained on treatment. Conclusions Patients experiencing deterioration of kidney function to a value below eGFR 30 mL/min/1.73 m2 faced high risk of cardiovascular and kidney disease outcomes. Continuation of sacubitril/valsartan was associated with persistent clinical benefit and no incremental safety risk. These data support continuation of sacubitril/valsartan for heart failure treatment even when eGFR declines below this threshold (PARADIGM-HF [Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure], NCT01035255; and PARAGON-HF [Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction], NCT01920711).
Item Type: | Articles |
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Status: | In Press |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | McMurray, Professor John |
Authors: | Chatur, S., Beldhuis, I. E., Claggett, B. L., McCausland, F. R., Neuen, B. L., Desai, A. S., Rouleau, J. L., Zile, M. R., Packer, M., Pfeffer, M. A., Lefkowitz, M. P., McMurray, J. J.V., Solomon, S. D., and Vaduganathan, M. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
Journal Name: | JACC: Heart Failure |
Publisher: | Elsevier |
ISSN: | 2213-1779 |
ISSN (Online): | 2213-1787 |
Published Online: | 05 June 2024 |
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