Evidence mapPaperPMID 41425656Full record

ArticleBiomedical reports2026

Cardiorenal safety and efficacy of angiotensin receptor-neprilysin inhibitors in heart failure across the ejection fraction spectrum: A meta-analysis and meta-regression of RCTs with 28,001 patients.

Derren D C H Rampengan, Stevanus C Surya, Kevin C Tjandra, Juan A J M N Lele, Starry H Rampengan, Ika N Kadariswantiningsih, Bulat Idrisov, Alina Idrisova, Maulana A Empitu

Abstract read
In one paragraph

Article in Biomedical reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Derren D C H RampenganMedical Doctor Program, Faculty of Medicine, Universitas Sam Ratulangi, Manado 95115, Indonesia.
Stevanus C SuryaMedical Doctor Program, Faculty of Medicine, Universitas Udayana, Denpasar 80232, Indonesia.
Kevin C TjandraMedical Doctor Program, Faculty of Medicine, Universitas Diponegoro, Semarang 50275, Indonesia.
Juan A J M N LeleMedical Doctor Program, Faculty of Medicine, Universitas Kristen Indonesia, Jakarta 10430, Indonesia.
Starry H RampenganDepartment of Cardiology and Vascular Medicine R.D. Kandou Central General Hospital, Faculty of Medicine, Universitas Sam Ratulangi, Manado 95115, Indonesia.
Ika N KadariswantiningsihFaculty of Medicine, Airlangga University, Surabaya, East Java 60131, Indonesia.
Bulat IdrisovHealth Services Research Department of Health Systems and Population Health, University of Washington, Seattle, Washington 98195, USA.
Alina IdrisovaHealth Services Research Department of Health Systems and Population Health, University of Washington, Seattle, Washington 98195, USA.
Maulana A EmpituFaculty of Medicine, Airlangga University, Surabaya, East Java 60131, Indonesia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Angiotensin receptor-neprilysin inhibitors (ARNIs), including sacubitril/valsartan, exert blood pressure-lowering and organ-protective effects in patients with heart failure (HF). However, differences of these effects across HF phenotypes and their impact on renal outcomes remain unclear. The present systematic review aimed to evaluate the antihypertensive efficacy, safety and cardiorenal benefits of ARNIs vs. angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) in patients with HF with reduced, mildly reduced, and preserved ejection fractions. Data were extracted from PubMed, Scopus, Cochrane, ProQuest and Google Scholar up to July 2025. Risk of bias was evaluated using the Cochrane Risk of Bias 2 tool. Meta-analyses were performed using risk ratios (RRs) with 95% confidence intervals (CIs). Data analyses were conducted using RevMan version 5.4 and STATA version 16.0. Outcomes encompassed all-cause mortality, cardiovascular mortality, HF-related hospitalization, major adverse cardiovascular events (MACEs) and adverse events. A total of 18 randomized control trials involving 28,001 patients were included. Compared with ACE-I/ARB, ARNI decreased all-cause (RR=0.67; 95% CI=0.83-0.97) and cardiovascular mortality (RR=0.84; 95% CI=0.77-0.92), HF hospitalization (RR=0.87; 95% CI=0.81-0.93) and MACE (RR=0.89; 95% CI=0.85-0.94), but increased symptomatic hypotension (RR=1.54; 95% CI=1.43-1.65). Subgroup analysis by left ventricular ejection fraction category did not reveal any significant effect modification across outcomes. Meta-regression identified N-terminal prohormone of brain natriuretic peptide (P=0.02) and body mass index (P<0.0001) as predictors of cardiovascular mortality. Estimated glomerular filtration rate was associated with all-cause mortality (P=0.001) and hypotension (P=0.03), while sex (P=0.001) predicted hospitalization. Systolic blood pressure (P=0.001) was linked to renal outcomes. Overall, ARNIs confer consistent cardiorenal benefits across the HF spectrum, particularly in patients with elevated systolic blood pressure and decreased renal function, though hypotension requires careful monitoring. The present study was registered in PROSPERO (registration no. CRD42024569374).

Indexed as

angiotensin receptor-neprilysin inhibitorheart failuremeta-analysissacubitril/valsartan

Identifiers

PMID41425656
PMCPMC12715665

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.