ABSTRACT
Background
The acute hemodynamic effects of sacubitril/valsartan, an angiotensin receptor neprilysin
inhibitor (ARNI), may result in early changes in kidney function, raising concerns
about acute kidney injury (AKI), particularly in those who are naïve to renin-angiotensin
system inhibitors (RASis).
Methods
We conducted a cohort study using U.S. Medicare fee-for-service claims data (2014–2017).
Patients with HFrEF ≥ 65 years newly initiating ARNI or RASi, with no prior use of
either drug class, were included. The primary outcome was hospitalization due to AKI
as the primary discharge diagnosis, and the secondary outcome included AKI as a primary
or secondary discharge diagnosis. AKI risks were described under an as-treated follow-up
approach, with censoring on treatment discontinuation, switch, insurance disenrollment,
death, or administrative censoring as well as an intent-to-treat approach. Propensity-score–based
fine-stratification weighting was used to account for potential confounding by 81
pre-exposure characteristics. Cumulative incidence functions were used to report absolute
risks, and Cox proportional hazards models were used to provide hazard ratios (HR)
and 95% confidence intervals (CI).
Results
We included 27,166 patients with a mean (SD) age of 73 (7.3) years, and 4155 (15.3%)
were initiating ARNI. After propensity score weighting, the 180-day cumulative incidence
was 2.7% (2.4%–3.1%) among RASi initiators and 2.7% (2.2%–3.5%) among ARNI initiators
for the primary outcome, and it was 6.5% (6.0%–7.1%) and 6.1% (5.2%–7.1%), respectively,
for the secondary outcome under as-treated follow-up. HR (95% CI) comparing ARNI with
RASi were 0.91 (95% CI: 0.72–1.16) for the primary outcome and 0.92 (95% CI: 0.79–1.08)
for the secondary outcome. Similar results were observed in the intent-to-treat analysis.
Conclusions
Among a large cohort of U.S. Medicare beneficiaries with HFrEF, ARNI treatment was
not associated with higher rates of AKI than RASi treatment. These results provide
reassurance for providers considering ARNI initiation in older patients who are RASi-naïve.
Graphical Abstract
Graphical Abstract
Key Words
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Article info
Publication history
Published online: September 30, 2022
Accepted:
September 12,
2022
Received in revised form:
September 12,
2022
Received:
July 21,
2022
Boston, MassachusettsPublication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 Elsevier Inc. All rights reserved.
ScienceDirect
Access this article on ScienceDirectLinked Article
- Renal Safety of de Novo Angiotensin-Neprilysin Inhibition in Older Adults: Insights From a Population-Based AnalysisJournal of Cardiac Failure
- PreviewThe PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure) trial established the angiotensin receptor neprilysin inhibitor (ARNI) sacubitril-valsartan as 1 of the 4 cornerstones of contemporary treatment for heart failure with reduced ejection fraction (HFrEF).1 Compared to angiotensin converting enzyme inhibitors (ACEIs), ARNIs reduced the risk of cardiovascular death or hospitalization due to HF by 20%. Despite the unequivocal efficacy and safety in PARADIGM-HF, broad uptake and maintenance of ARNI therapy has been suboptimal in clinical practice.
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