Research

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: 

• Scott D. Solomon (Brigham and Women’s Hospital)    
• John J.V. McMurray (University of Glasgow)

Internal Investigators: 

• Prof John Cleland - UK National Leader
• Dr Pardeep Jhund

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:        

PUBLICATION:
https://www.nejm.org/doi/full/10.1056/NEJMoa1409077

PI:
Prof John McMurray 

Press releases:

https://www.brighamandwomens.org

https://www.escardio.org/

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

SCMH News: 
https://www.gla.ac.uk/schools/cardiovascularmetabolic/newsandevents/march-may2020/headline_725046_en.html

PARAGON-HF: https://www.nejm.org/doi/full/10.1056/NEJMoa1409077 

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 Selvaraj, Brian L Claggett, Michael Böhm, Stefan D Anker, Muthiah Vaduganathan, Faiez Zannad, Burkert Pieske, Carolyn S P Lam, Inder S Anand, Victor C Shi, Martin P Lefkowitz, John J V McMurray, Scott 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 Vaduganathan, Pardeep S Jhund, Brian L Claggett, Milton Packer, Jiri Widimský, Petar Seferovic, Adel Rizkala, Martin Lefkowitz, Victor Shi, John J V McMurray, Scott D Solomon
   
   European heart journal - https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehaa184/5813082 

NOVEMBER 2020

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 McMurray, Alice M Jackson, Carolyn S P Lam, Margaret M Redfield, Inder S Anand, Junbo Ge, Marty P Lefkowitz, Aldo P Maggioni, Felipe Martinez , Milton Packer, Marc A Pfeffer, Burkert Pieske, Adel R Rizkala, Shalini V Sabarwal, Amil M Shah, Sanjiv J Shah, Victor C Shi, Dirk J van Veldhuisen, Faiez Zannad, Michael R Zile, Maja Cikes, Eva Goncalvesova, Tzvetana Katova, Anamaria Kosztin, Malgorzata Lelonek, Nancy Sweitzer, Orly Vardeny, Brian Claggett, Pardeep S Jhund, Scott 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 Solomon, Muthiah Vaduganathan, Brian L Claggett, Milton Packer, Michael Zile , Karl Swedberg, Jean Rouleau, Marc A Pfeffer, Akshay Desai, Lars H Lund, Lars Kober, Inder Anand, Nancy Sweitzer, Gerard Linssen, Bela Merkely, Juan Luis Arango, Dragos Vinereanu, Chen-Huan Chen, Michele Senni, Antonio Sibulo , Sergey Boytsov, Victor Shi, Adel Rizkala, Martin Lefkowitz, John J V McMurray.
   
   Circulation - https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.044586

1. Prior Heart Failure Hospitalization, Clinical Outcomes, and Response to Sacubitril/Valsartan Compared With Valsartan in HFpEF.
   Muthiah Vaduganathan, Brian L Claggett, Akshay S Desai, Stefan D Anker, Sergio V Perrone, Stefan Janssens, Davor Milicic, Juan L Arango, Milton Packer, Victor C Shi, Martin P Lefkowitz, John J V McMurray, Scott D Solomon.
   
   Journal of the American College of Cardiology - https://www.onlinejacc.org/content/75/3/245

SEPTEMBER 2019

1. Efficacy and Safety of Dapagliflozin in Heart Failure With Reduced Ejection Fraction According to Age.
   Insights From DAPA-HF
   Felipe A Martinez, Matteo Serenelli, Jose C Nicolau, Mark C Petrie, Chern-En Chiang, Sergey Tereshchenko, Scott D Solomon, Silvio E Inzucchi, Lars Køber, Mikhail N Kosiborod, Piotr Ponikowski, Marc S Sabatine, David L DeMets, MonikaDutkiewicz-Piasecka, OlofBengtsson, Mikaela Sjöstrand, Anna Maria Langkilde, Pardeep S Jhund, John 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 Kosiborod, Pardeep S Jhund, Kieran F Docherty, Mirta Diez, Mark C Petrie, Subodh Verma, Jose C Nicolau, Béla Merkely, Masafumi Kitakaze, David L DeMets, Silvio E Inzucchi, Lars Køber, Felipe A Martinez, Piotr Ponikowski, Marc S Sabatine, Scott D Solomon, Olof Bengtsson, Daniel Lindholm, Anna Niklasson, Mikaela Sjöstrand, Anna Maria Langkilde, John J V McMurray.  
   
   Circulation - https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.044138

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