ABSTRACT
Background
A substantial proportion of patients with heart failure and kidney disease have poorly
controlled blood pressures. This study aimed to evaluate patterns of blood pressure
after initiation of an angiotensin receptor neprilysin inhibitor (ARNI) or an angiotensin-converting
enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) across the spectrum of
kidney function.
Methods
Between 2016 and 2020, we evaluated 26,091 patients admitted to a Veterans Affairs
hospital for an acute heart failure exacerbation with reduced ejection fraction. We
assessed patterns of systolic and diastolic blood pressure among those started on
ARNI or ACEI/ARB over 6 months, overall and across estimated glomerular filtration
rate (eGFR). To account for differential treatment factors, we applied 1:1 propensity
score matching using 15 known baseline covariates.
Results
There were 13,781 individuals treated with an ACEI or ARB and 2589 individuals treated
with an ARNI prescription. After propensity score matching, 839 patients were matched
in each of the ARNI and ACEI/ARB groups. Mean baseline estimated glomerular filtration
rate (eGFR) was 63.8 (standard deviation 21.6), and 10% had stage 4 or 5 chronic kidney
disease. Patients in the ARNI group experienced greater systolic blood pressure reduction
at month 3 (-5.2 mmHg vs -2.2 mmHg, ARNI vs ACEI/ARB; P < 0.001), and month 6 (-4.7 mmHg vs -1.85 mmHg, ARNI vs ACEI/ARB; P < 0.001). These differences in systolic blood pressure by 6 months did not vary by
eGFR above and below 60 mL/min/1.73m2 or continuously across a wide range of eGFR (Pinteraction > 0.10 for both).
Conclusion
The use of ARNI was associated with significant reduction in blood pressure as compared
to the ACEI/ARB group overall and across the eGFR spectrum, including in advanced
chronic kidney disease.
Graphical abstract

Graphical Abstract
Key Words
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References
- Sacubitril-valsartan as a treatment for apparent resistant hypertension in patients with heart failure and preserved ejection fraction.Eur Heart J. 2021; 42: 3741-3752
- Effects of Sacubitril/Valsartan Versus Olmesartan on Central Hemodynamics in the Elderly With Systolic Hypertension: the PARAMETER Study.Hypertension. 2017; 69: 411-420
- A Randomized trial of intensive versus standard blood-pressure control.N Engl J Med. 2015; 373: 2103-2116
- 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: Executive Summary: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.J Am Coll Cardiol. 2022;
- Blood pressure and glycemic control among ambulatory US adults with heart failure: National Health and Nutrition Examination Survey 2001 to 2018.Circ Heart Fail. 2022; (101161circheartfailure121009229)
- Angiotensin-neprilysin inhibition versus enalapril in heart failure.N Engl J Med. 2014; 371: 993-1004
- Role of neprilysin inhibitor combinations in hypertension: insights from hypertension and heart failure trials.Eur Heart J. 2015; 36: 1967-1973
- Effects of sacubitril/valsartan versus irbesartan in patients with chronic kidney disease.Circulation. 2018; 138: 1505-1514
- Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction.N Engl J Med. 2019; 381: 1609-1620
- Arterial stiffness and kidney function.Hypertension. 2004; 43: 163-168
- Resistant hypertension in CKD.Clin J Am Soc Nephrol. 2021; 16: 467-469
- Aortic PWV in chronic kidney disease: a CRIC ancillary study.Am J Hypertens. 2010; 23: 282-289
- From ARB to ARNI in cardiovascular control.Curr Hypertens Rep. 2016; 18: 86
- Patterns of use and clinical outcomes with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in acute heart failure and changes in kidney function: an analysis of the Veterans’ Health Administrative Database.Cardiorenal Med. 2021; 11: 226-236
- New creatinine- and cystatin c-based equations to estimate GFR without ace.N Engl J Med. 2021; 385: 1737-1749
- Multivariate Imputation by Chained Equations in R.J Statist Softw. 2011; 45: 1-67
- MatchIt: nonparametric preprocessing for parametric causal inference.J Statist Softw. 2011; 42: 1-28
- Visualization of regression models using visage.R J. 2017; 9: 56-71https://doi.org/10.32614/RJ-2017-046
- Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline.Ann Intern Med. 2013; 158: 825-830
- 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.Hypertension. 2018; 71 (Jr): 1269-1324
- Omapatrilat and enalapril in patients with hypertension: the Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) trial.Am J Hypertens. 2004; 17: 103-111
- Angiotensin-neprilysin inhibition versus enalapril in heart failure.N Engl J Med. 2014; 371: 993-1004
- Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction.N Engl J Med. 2019; 381: 1609-1620
- Effects of age and sex on the pharmacokinetics of LCZ696, an angiotensin receptor neprilysin inhibitor.J Clin Pharmacol. 2016; 56: 78-86
- Sex-related differences in the pharmacological treatment of heart failure.Pharmacol Therapeut. 2022; 229107891
- Hyperkalemia associated with use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.Cardiovasc Ther. 2012; 30: e156-e166
- Management of hypertension in chronic kidney disease.Drugs. 2019; 79: 365-379
- Angiotensin-neprilysin inhibition in acute decompensated heart failure.N Engl J Med. 2018; 380: 539-548
Article info
Publication history
Published online: December 10, 2022
Accepted:
October 25,
2022
Received in revised form:
October 19,
2022
Received:
June 15,
2022
Albany and New York, New York; Columbia, South Carolina; Loma Linda, California; Minneapolis, Minnesota; Philadelphia, Pennsylvania; Boston, Massachusetts; and Washington, D.C.Identification
Copyright
Published by Elsevier Inc.