Evidence map›Paper›PMID 23563576›Full record

Trial reportEuropean journal of heart failure2013

Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure: rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF).

John J V McMurray, Milton Packer, Akshay S Desai, Jim Gong, Martin P Lefkowitz, Adel R Rizkala, Jean Rouleau, Victor C Shi, Scott D Solomon, Karl Swedberg and 2 more

Registry-linked trialOpen access · hybridAbstract readComparative StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in European journal of heart failure, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01035255 (A Multicenter, Randomized, Double-blind, Parallel Group, Active-controlled Study to Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality in Patients With Chronic Heart Failure and Reduced Ejection Fraction), which is not on this map. Cited by 179 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
179citing papers in PubMed, 8 pooled it
23.1field-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.

NCT01035255 phase3terminatednot on this map

A Multicenter, Randomized, Double-blind, Parallel Group, Active-controlled Study to Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality in Patients With Chronic Heart Failure and Reduced Ejection Fraction

TypeinterventionalSponsorNovartis PharmaceuticalsRan2009 to 2014Enrolled8,442ConditionsHeart Failure With Reduced Ejection FractionArmsLCZ696 200 mg BID, Enalapril 10 mg BID
3 · Its place in the literature

Who cites it

179 citing papers in PubMed, 8 syntheses or guidelines pooled it, 449 citations in OpenAlex.

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  4. NT-proBNP in Different Patient Groups of COPD: A Systematic Review and Meta-Analysis.International journal of chronic obstructive pulmonary disease · 2023
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  16. Optimizing heart failure treatment following cardiac resynchronization therapy.Clinical research in cardiology : official journal of the German Cardiac Society · 2020
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119 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

12 authors at 8 institutions in 5 countries.

John J V McMurrayBHF Cardiovascular Research Centre, University of Glasgow, UK. john.mcmurray@glasgow.ac.uk
Milton Packer
Akshay S Desai
Jim Gong
Martin P Lefkowitz
Adel R Rizkala
Jean Rouleau
Victor C Shi
Scott D Solomon
Karl Swedberg
Michael R Zile
PARADIGM-HF Committees and Investigators
Harvard University Press · USNovartis (United States) · USTris Pharma (United States) · USMedical University of South Carolina · USThe University of Texas Southwestern Medical Center · USUniversité de Montréal · CAUniversity of Glasgow · GBUniversity of Gothenburg · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsAlthough the focus of therapeutic intervention has been on neurohormonal pathways thought to be harmful in heart failure (HF), such as the renin-angiotensin-aldosterone system (RAAS), potentially beneficial counter-regulatory systems are also active in HF. These promote vasodilatation and natriuresis, inhibit abnormal growth, suppress the RAAS and sympathetic nervous system, and augment parasympathetic activity. The best understood of these mediators are the natriuretic peptides which are metabolized by the enzyme neprilysin. LCZ696 belongs to a new class of drugs, the angiotensin receptor neprilysin inhibitors (ARNIs), which both block the RAAS and augment natriuretic peptides.

methodsPatients with chronic HF, NYHA class II-IV symptoms, an elevated plasma BNP or NT-proBNP level, and an LVEF of ≤40% were enrolled in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortailty and morbidity in Heart Failure trial (PARADIGM-HF). Patients entered a single-blind enalapril run-in period (titrated to 10 mg b.i.d.), followed by an LCZ696 run-in period (100 mg titrated to 200 mg b.i.d.). A total of 8436 patients tolerating both periods were randomized 1:1 to either enalapril 10 mg b.i.d. or LCZ696 200 mg b.i.d. The primary outcome is the composite of cardiovascular death or HF hospitalization, although the trial is powered to detect a 15% relative risk reduction in cardiovascular death. PERSPECTIVES: PARADIGM-HF will determine the place of the ARNI LCZ696 as an alternative to enalapril in patients with systolic HF. PARADIGM-HF may change our approach to neurohormonal modulation in HF.

trial registrationNCT01035255.

Indexed as

AminobutyratesAngiotensin-Converting Enzyme InhibitorsAngiotensin Receptor AntagonistsBiphenyl CompoundsDrug CombinationsEnalaprilHeart Failure, SystolicHospitalizationHumansMorbidityNatriuretic Peptide, BrainNeprilysinPeptide FragmentsProspective StudiesSingle-Blind MethodSurvival RateAminobutyratesAngiotensin-Converting Enzyme InhibitorsAngiotensin Receptor AntagonistsBiphenyl CompoundsDrug CombinationsEnalaprilNatriuretic Peptide, BrainNeprilysinPeptide Fragmentspro-brain natriuretic peptide (1-76)sacubitril and valsartan sodium hydrate drug combinationTetrazolesValsartanACE inhibitorAngiotensin receptor blockerAngiotensin receptor neprilysin inhibitorChronic heart failureLCZ696Natriuretic peptidesNeprilysinNeutral endopeptidaseRenin–angiotensin

Identifiers

PMID23563576
PMCPMC3746839
OpenAlexW2098418963

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

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.