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Trial Summary

PARAGON-HF: Prospective comparison of ARni with Arb Global Outcomes in heart failure with preserved ejectioN fraction

'Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction'

PARAGON-HF was presented at the ESC Congress in Paris on 1 September. This trial, sponsored by Novartis, ran from July 2014 to June 2019 and was led by Professor Scott Solomon of the Brigham and Women’s Hospital and Harvard Medical School, Boston, and Professor John McMurray .

Its purpose was to evaluate the effect of sacubitril/valsartan (LCZ696) compared to valsartan in the reduction of cardiovascular death and heart failure (HF) hospitalizations in patients with HF with preserved ejection fraction. Whilst the angiotensin neprilysin inhibitor sacubitril/valsartan narrowly missed its primary endpoint of reducing total hospitalisation and cardiovascular death in patients with heart failure with preserved ejection fraction (HFpEF), the data suggests there may be benefit in some patient groups, i.e. women and patients with lower ejection fraction.

Papers have been published in New England Journal of Medicine, Journal of the American College of Cardiology, Circulation and Circulation Heart Failure.


Co-principal Investigators: 

Internal Investigators: 

External Co-Investigators:            

  • Milton Packer, M.D., 
  • Akshay S. Desai, M.D., M.P.H., 
  • Jianjian Gong, Ph.D., 
  • Martin P. Lefkowitz, M.D., 
  • Adel R. Rizkala, Pharm.D., 
  • Jean L. Rouleau, M.D., 
  • Victor C. Shi, M.D., 
  • Scott D. Solomon, M.D., 
  • Karl Swedberg, M.D., Ph.D., 
  • and Michael R. Zile, M.D.

Trial Co-Ordinator:        



MARCH 2020

While presenting DAPA-HF at The American College of Cardiology virtual Congress the HF group simultaneous had PARAGON-HF publications in the top journals including JACC and the European Heart Journal.

  1. Systolic Blood Pressure in Heart Failure With Preserved Ejection Fraction Treated With Sacubitril/Valsartan.
    Senthil SelvarajBrian L ClaggettMichael BöhmStefan D AnkerMuthiah VaduganathanFaiez ZannadBurkert PieskeCarolyn S P LamInder S AnandVictor C ShiMartin P LefkowitzJohn J V McMurrayScott D Solomon

    Journal of the American College of Cardiology -

  2. A putative placebo analysis of the effects of sacubitril/valsartan in heart failure across the full range of ejection fraction.
    Muthiah VaduganathanPardeep S JhundBrian L ClaggettMilton PackerJiri WidimskýPetar SeferovicAdel RizkalaMartin LefkowitzVictor ShiJohn J V McMurrayScott D Solomon

    European heart journal - 


SCMH Heart failure group published 3 papers from PARAGON-HF in leading cardiology journals simultaneously with presentations at the Scientific Sessions of the American Heart Association in Philadelphia, November 16–18

  1. Effects of sacubitril-valsartan, versus valsartan, in women compared to men with heart failure and preserved ejection fraction: Insights from PARAGON-HF.
    John J V McMurrayAlice M JacksonCarolyn S P LamMargaret M RedfieldInder S AnandJunbo GeMarty P LefkowitzAldo P MaggioniFelipe Martinez Milton PackerMarc A PfefferBurkert PieskeAdel R RizkalaShalini V SabarwalAmil M ShahSanjiv J ShahVictor C ShiDirk J van VeldhuisenFaiez ZannadMichael R ZileMaja CikesEva GoncalvesovaTzvetana KatovaAnamaria KosztinMalgorzata LelonekNancy SweitzerOrly VardenyBrian ClaggettPardeep S JhundScott D Solomon.

    Circulation -

  2. Sacubitril/Valsartan Across the Spectrum of Ejection Fraction in Heart Failure.
    Scott D SolomonMuthiah VaduganathanBrian L ClaggettMilton PackerMichael Zile Karl SwedbergJean RouleauMarc A PfefferAkshay DesaiLars H LundLars KoberInder AnandNancy SweitzerGerard LinssenBela MerkelyJuan Luis ArangoDragos VinereanuChen-Huan ChenMichele SenniAntonio Sibulo Sergey BoytsovVictor ShiAdel RizkalaMartin LefkowitzJohn J V McMurray.

    Circulation -
  1. Prior Heart Failure Hospitalization, Clinical Outcomes, and Response to Sacubitril/Valsartan Compared With Valsartan in HFpEF.
    Muthiah VaduganathanBrian L ClaggettAkshay S DesaiStefan D AnkerSergio V PerroneStefan JanssensDavor MilicicJuan L ArangoMilton PackerVictor C ShiMartin P LefkowitzJohn J V McMurrayScott D Solomon.

    Journal of the American College of Cardiology -


  1. Efficacy and Safety of Dapagliflozin in Heart Failure With Reduced Ejection Fraction According to Age.
    Insights From DAPA-HF
    Felipe A MartinezMatteo SerenelliJose C NicolauMark C PetrieChern-En ChiangSergey TereshchenkoScott D SolomonSilvio E InzucchiLars KøberMikhail N KosiborodPiotr PonikowskiMarc S SabatineDavid L DeMetsMonikaDutkiewicz-PiaseckaOlofBengtssonMikaela SjöstrandAnna Maria LangkildePardeep S JhundJohn J V McMurray.

    Circulation -

  2. Effects of dapagliflozin on symptoms, function and quality of life in patients with heart failure and reduced ejection fraction: results from the DAPA-HF Trial.
    Mikhail N KosiborodPardeep S JhundKieran F DochertyMirta DiezMark C PetrieSubodh VermaJose C NicolauBéla MerkelyMasafumi KitakazeDavid L DeMetsSilvio E InzucchiLars KøberFelipe A MartinezPiotr PonikowskiMarc S SabatineScott D SolomonOlof BengtssonDaniel LindholmAnna NiklassonMikaela SjöstrandAnna Maria LangkildeJohn J V McMurray.  

    Circulation -

SEPT 2019

PARAGON-HF was also presented at the ESC Congress in Paris on 1 September. This trial, sponsored by Novartis, ran from July 2014 to June 2019 and was led by Professor John McMurray and Professor Scott Solomon, of Harvard Medical School in Boston.

'Preserved Heart Failure Trial Misses Endpoint, But Drug May Benefit Some Patients Overall.'

sacubitril-valsartan did not significantly reduce hospitalizations and cardiovascular death in patients with heart failure with preserved ejection fraction; however, some patient groups benefited from the therapy i.e. women and patients with lower ejection fraction.

Link to full list of publications