SCMH Clinical Trials: DAPA-HF & PARAGON-HF

Two major heart failure studies came to fruition in 2019:

  1. Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure (DAPA-HF).
  2. Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction (PARAGON-HF).

DAPA-HF: Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure

'Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients with Chronic Heart Failure with Reduced Ejection Fraction'

1 Sept 2019:

Dapagliflozin reduces death and hospitalisation in patients with heart failure and reduced ejection fraction with and without diabetes. The late breaking results of the DAPA-HF trial were presented in a Hot Line Session at ESC Congress 2019 together with the World Congress of Cardiology.

dapa HF results

Principal investigator Professor John McMurray said: “The most important finding of all is the benefit in patients without diabetes. This is truly a treatment for heart failure and not just a drug for diabetes.”

Full UofG news story https://www.gla.ac.uk/news/headline_669254_en.html
NEJM Paper : https://www.nejm.org/doi/full/10.1056/NEJMoa1911303

16 Nov 2019:

SCMH Heart failure group published 2 papers from DAPA-HF in a leading cardiology journal simultaneously with presentations at the Scientific Sessions of the American Heart Association in Philadelphia, November 16–18

  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 - https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.119.044133

  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 - https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.044138

28 March 2020:

The American College of Cardiology Congress –Virtual, included presentations and posters from the HF group, 

  1. Effect of Dapagliflozin on Worsening Heart Failure and Cardiovascular Death in Patients With Heart Failure With and Without Diabetes. view online here:  https://jamanetwork.com/journals/jama/fullarticle/2763950
  2. Effects of dapagliflozin in DAPA-HF according to background heart failure therapy. View online here: https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehaa183/5813081

21 May 2020:

Estimating the cumulative survival advantage of the 3 newest life-saving treatments in Heart Failure - each shown to be of benefit in trials the HF group were involved in leading.

Estimating lifetime benefits of comprehensive disease-modifying pharmacological therapies in patients with heart failure with reduced ejection fraction: a comparative analysis of three randomised controlled trials
Online - https://www.sciencedirect.com/science/article/pii/S0140673620307480#!

overall survival stats 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'

1 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.

paragon-hf outcome chart

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

The New England Journal of Medicine (NEJM) - https://www.nejm.org/doi/full/10.1056/NEJMoa1409077

Press releases:
https://www.brighamandwomens.org
https://www.escardio.org/

UofG News story: https://www.gla.ac.uk/news/headline_669241_en.html

16 Nov 2019:

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 - https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.044586

  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 - https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.044586

  3. 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 Perrone Stefan JanssensDavor MilicicJuan L ArangoMilton PackerVictor C ShiMartin P LefkowitzJohn J V McMurrayScott D Solomon.

    Journal of the American College of Cardiology - https://www.onlinejacc.org/content/75/3/245

 

28 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 - https://www.onlinejacc.org/content/75/14/1644

  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 - https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehaa184/5813082

 


First published: 5 June 2020