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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References
- Angiotensin-neprilysin inhibition versus enalapril in heart failure.N Engl J Med. 2014; 371: 993-1004
- Sacubitril/valsartan use patterns among older adults with heart failure in clinical practice: a population-based cohort study of >25,000 Medicare beneficiaries.Eur J Heart Fail. 2022; 24 (Epub 2022 Jun 22. PMID: 35689603): 1506-1515https://doi.org/10.1002/ejhf.2572
- Treatment persistence of renin-angiotensin-aldosterone-system inhibitors over time in heart failure with reduced ejection fraction.J Card Fail. 2022; 28 (Epub 2021 Aug 21. PMID: 34428591): 191-201https://doi.org/10.1016/j.cardfail.2021.08.008
- A basic study design for expedited safety signal evaluation based on electronic healthcare data.Pharmacoepidemiol Drug Saf. 2010; 19: 858-868
- Development and preliminary validation of a medicare claims-based model to predict left ventricular ejection fraction class in patients with heart failure.Circ Cardiovasc Qual Outcomes. 2018; 11e004700
- Declining mortality in patients with acute renal failure, 1988 to 2002.J Am Soc Nephrol. 2006; 17: 1143-1150
- A propensity-score-based fine stratification approach for confounding adjustment when exposure is infrequent.Epidemiology. 2017; 28: 249-257
- Introduction to the analysis of survival data in the presence of competing risks.Circulation. 2016; 133: 601-609
- Angiotensin-neprilysin inhibition in acute decompensated heart failure.N Engl J Med. 2019; 380 (Epub 2018 Nov 11. Erratum in: N Engl J Med. 2019 Mar 14;380(11):1090. PMID: 30415601): 539-548https://doi.org/10.1056/NEJMoa1812851
- Renal outcomes in patients with systolic heart failure treated with sacubitril-valsartan or angiotensin converting enzyme inhibitor/angiotensin receptor blocker.Mayo Clin Proc Innov Qual Outcomes. 2021; 5: 286-297
- Renal effects and associated outcomes during angiotensin-neprilysin inhibition in heart failure.JACC Heart Fail. 2018; 6: 489-498
- Epidemiologic characterization of heart failure with reduced or preserved ejection fraction populations identified using Medicare claims.Am J Med. 2021; 134 (Epub 2020 Oct 27. PMID: 33127370): e241-e251https://doi.org/10.1016/j.amjmed.2020.09.038
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.
