Evidence map›Paper›PMID 26231885›Full record

Trial reportEuropean heart journal2015

Efficacy and safety of LCZ696 (sacubitril-valsartan) according to age: insights from PARADIGM-HF.

Pardeep S Jhund, Michael Fu, Edmundo Bayram, Chen-Huan Chen, Marta Negrusz-Kawecka, Arvo Rosenthal, Akshay S Desai, Martin P Lefkowitz, Adel R Rizkala, Jean L Rouleau and 7 more

Open access · hybridAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in European heart journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed, 4 pooled it
19.3field-weighted citation impact, top 1% of its field
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

99 citing papers in PubMed, 4 syntheses or guidelines pooled it, 222 citations in OpenAlex.

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  13. Heart Failure in Older Patients: An Update.Journal of clinical medicine · 2025
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39 more citing papers are in PubMed but not listed here.

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

17 authors at 11 institutions in 6 countries.

Pardeep S JhundBHF Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK.
Michael FuDepartment of Medicine, Sahlgrenska University Hospital/Östra Hospital, Göteborg, Sweden.
Edmundo BayramFundación Cardiovascular de Aguascalientes A.C., México.
Chen-Huan ChenDepartment of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China.
Marta Negrusz-KaweckaDepartment and Clinic of Cardiology, Wroclaw Medical University, Wroclaw, Poland.
Arvo RosenthalDr. Arvo Rosenthal LLC, Estonia.
Akshay S DesaiCardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Martin P LefkowitzNovartis Pharmaceutical Corporation, East Hanover, NJ, USA.
Adel R RizkalaNovartis Pharmaceutical Corporation, East Hanover, NJ, USA.
Jean L RouleauInstitut de Cardiologie de Montréal, Université de Montréal, Montréal, Canada.
Victor C ShiNovartis Pharmaceutical Corporation, East Hanover, NJ, USA.
Scott D SolomonCardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Karl SwedbergDepartment of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden National Heart and Lung Institute, Imperial College, London, UK.
Michael R ZileMedical University of South Carolina and RHJ Department of Veterans Administration Medical Center, Charleston, SC, USA.
John J V McMurrayBHF Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK john.mcmurray@glasgow.ac.uk.
Milton PackerDepartment of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
PARADIGM-HF Investigators and Committees
Novartis (United States) · USUniversity of Glasgow · GBBrigham and Women's Hospital · USHarvard University Press · USMedical University of South Carolina · USMontreal Heart Institute · CASahlgrenska University Hospital · SETaipei Veterans General Hospital · TWThe University of Texas Southwestern Medical Center · USUniversity of Gothenburg · SEWroclaw Medical University · PL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe age at which heart failure develops varies widely between countries and drug tolerance and outcomes also vary by age. We have examined the efficacy and safety of LCZ696 according to age in the Prospective comparison of angiotensin receptor neprilysin inhibitor with angiotensin converting enzyme inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF).

methodsIn PARADIGM-HF, 8399 patients aged 18-96 years and in New York Heart Association functional class II-IV with an LVEF ≤40% were randomized to either enalapril or LCZ696. We examined the pre-specified efficacy and safety outcomes according to age category (years): <55 (n = 1624), 55-64 (n = 2655), 65-74 (n = 2557), and ≥75 (n = 1563).

findingsThe rate (per 100 patient-years) of the primary outcome of cardiovascular (CV) death or heart failure hospitalization (HFH) increased from 13.4 to 14.8 across the age categories. The LCZ696:enalapril hazard ratio (HR) was <1.0 in all categories (P for interaction between age category and treatment = 0.94) with an overall HR of 0.80 (0.73, 0.87), P < 0.001. The findings for HFH were similar for CV and all-cause mortality and the age category by treatment interactions were not significant. The pre-specified safety outcomes of hypotension, renal impairment and hyperkalaemia increased in both treatment groups with age, although the differences between treatment (more hypotension but less renal impairment and hyperkalaemia with LCZ696) were consistent across age categories.

interpretationLCZ696 was more beneficial than enalapril across the spectrum of age in PARADIGM-HF with a favourable benefit-risk profile in all age groups.

Indexed as

AdolescentAdultAgedAged, 80 and overAge FactorsAminobutyratesAngiotensin Receptor AntagonistsBiphenyl CompoundsCause of DeathDrug CombinationsHeart FailureHumansMiddle AgedTetrazolesTreatment OutcomeValsartanAminobutyratesAngiotensin Receptor AntagonistsBiphenyl CompoundsDrug Combinationssacubitril and valsartan sodium hydrate drug combinationTetrazolesValsartanAgeAngiotensinHeart failureNeprilysinReceptors

Identifiers

PMID26231885
PMCPMC4595742
OpenAlexW1862226808

What OpenQuestion holds

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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 OpenQuestion graph.