Evidence map›Paper›PMID 29431251›Full record

Trial reportEuropean journal of heart failure2018

Effect of sacubitril/valsartan on recurrent events in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF).

Ulrik M Mogensen, Jianjian Gong, Pardeep S Jhund, Li Shen, Lars Køber, Akshay S Desai, Martin P Lefkowitz, Milton Packer, Jean L Rouleau, Scott D Solomon and 5 more

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

Trial report in European journal of heart failure, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 3 pooled it
8.0field-weighted citation impact, top 2% 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

48 citing papers in PubMed, 3 syntheses or guidelines pooled it, 77 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Highlights in heart failure.ESC heart failure · 2019
    Pooled it
  4. Trial
  5. Trial
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  7. Meta-analysis of RAAS inhibition in patients with a systemic right ventricle.International journal of cardiology. Congenital heart disease · 2026
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  9. Review
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  14. Observational
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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

15 authors at 10 institutions in 6 countries.

Ulrik M MogensenBHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
Jianjian GongNovartis Pharmaceutical Corporation, East Hanover, NJ, USA.
Pardeep S JhundBHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
Li ShenBHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
Lars KøberRigshospitalet Copenhagen University Hospital, Copenhagen, Denmark.
Akshay S DesaiCardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Martin P LefkowitzNovartis Pharmaceutical Corporation, East Hanover, NJ, USA.
Milton PackerBaylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, TX, USA.
Jean L RouleauInstitut de Cardiologie de Montréal, Université de Montréal, Montréal, Canada.
Scott D SolomonCardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Brian L ClaggettCardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Karl SwedbergDepartment of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden, and National Heart and Lung Institute, Imperial College, London, UK.
Michael R ZileMedical University of South Carolina and Ralph H. Johnson Veterans Administration Medical Center, Charleston, SC, USA.
Guenther Mueller-VeltenNovartis Pharma AG, Basel, Switzerland.
John J V McMurrayBHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
Brigham and Women's Hospital · USUniversity of Glasgow · GBNovartis (United States) · USBaylor University Medical Center · USCopenhagen University Hospital · DKImperial College London · GBNovartis (Switzerland) · CHRalph H. Johnson VA Medical Center · USRigshospitalet · DKUniversité de Montréal · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsRecurrent hospitalizations are a major part of the disease burden in heart failure (HF), but conventional analyses consider only the first event. We compared the effect of sacubitril/valsartan vs. enalapril on recurrent events, incorporating all HF hospitalizations and cardiovascular (CV) deaths in PARADIGM-HF, using a variety of statistical approaches advocated for this type of analysis. METHODS AND

resultsIn PARADIGM-HF, a total of 8399 patients were randomized and followed for a median of 27 months. We applied various recurrent event analyses, including a negative binomial model, the Wei, Lin and Weissfeld (WLW), and Lin, Wei, Ying and Yang (LWYY) methods, and a joint frailty model, all adjusted for treatment and region. Among a total of 3181 primary endpoint events (including 1251 CV deaths) during the trial, only 2031 (63.8%) were first events (836 CV deaths). Among a total of 1195 patients with at least one HF hospitalization, 410 (34%) had at least one further HF hospitalization. Sacubitril/valsartan compared with enalapril reduced the risk of recurrent HF hospitalization using the negative binomial model [rate ratio (RR) 0.77, 95% confidence interval (CI) 0.67-0.89], the WLW method [hazard ratio (HR) 0.79, 95% CI 0.71-0.89], the LWYY method (RR 0.78, 95% CI 0.68-0.90), and the joint frailty model (HR 0.75, 95% CI 0.66-0.86) (all P < 0.001). The effect of sacubitril/valsartan vs. enalapril on recurrent HF hospitalizations/CV death was similar.

conclusionsIn PARADIGM-HF, approximately one third of patients with a primary endpoint (time-to-first) experienced a further event. Compared with enalapril, sacubitril/valsartan reduced both first and recurrent events. The treatment effect size was similar, regardless of the statistical approach applied.

Indexed as

AgedAminobutyratesAngiotensin-Converting Enzyme InhibitorsAngiotensin Receptor AntagonistsBiphenyl CompoundsDose-Response Relationship, DrugDrug CombinationsEnalaprilEuropeFemaleHeart FailureHumansMaleMiddle AgedMorbidityProspective StudiesAminobutyratesAngiotensin-Converting Enzyme InhibitorsAngiotensin Receptor AntagonistsBiphenyl CompoundsDrug CombinationsEnalaprilsacubitril and valsartan sodium hydrate drug combinationTetrazolesValsartanHeart failureHospitalizationNeprilysin inhibitorRecurrent events

Identifiers

PMID29431251
PMCPMC6607507
OpenAlexW2793844490

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.