Joanne Simpson1, Pardeep S Jhund1, Jose Silva Cardoso2, Felipe Martinez3, Arend Mosterd4, Felix Ramires5, Adel R Rizkala6, Michele Senni7, Iain Squire8, Jianjian Gong6, Martin P Lefkowitz6, Victor C Shi6, Akshay S Desai9, Jean L Rouleau10, Karl Swedberg11, Michael R Zile12, John J V McMurray13, Milton Packer14, Scott D Solomon9. 1. BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom. 2. Department of Cardiology, Porto Medical School, São João Hospital, Porto, Portugal. 3. Instituto DAMIC, Cordoba National University, Córdoba, Argentina. 4. Meander Medical Center, Amersfoort and WCN-Dutch Network for Cardiovascular Research, Utrecht, the Netherlands. 5. Heart Institute, University of São Paulo, São Paulo, Brazil. 6. Novartis Pharmaceutical Corporation, East Hanover, New Jersey. 7. Cardiology, Heart Failure and Heart Transplantation Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy. 8. University of Leicester, Department of Cardiovascular Sciences and NIHR Cardiovascular, Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom. 9. Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts. 10. Institut de Cardiologie, Université de Montréal, Montréal, Québec, Canada. 11. Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden. 12. Medical University of South Carolina and RHJ Department of Veterans Administration Medical Center, Charleston, South Carolina. 13. BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom. Electronic address: john.mcmurray@glasgow.ac.uk. 14. Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas.
Abstract
BACKGROUND: Although most patients in the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial had mild symptoms, there is a poor correlation between reported functional limitation and prognosis in heart failure. OBJECTIVES: The aim of this study was to examine the spectrum of risk in PARADIGM-HF and the effect of LCZ696 across that spectrum. METHODS: This study analyzed rates of the primary composite outcome of cardiovascular death or heart failure hospitalization, its components, and all-cause mortality using the MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) and EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) risk scores to categorize patients. The authors determined whether risk, on the basis of these scores, modified the treatment effect of LCZ696. RESULTS: The complete MAGGIC risk score was available for 8,375 of the 8,399 patients in PARADIGM-HF. The median MAGGIC score was 20 (IQR: 16 to 24). An increase of 1 point was associated with a 6% increased risk for the primary endpoint (p < 0.001) and a 7% increased risk for cardiovascular death (p < 0.001). The benefit of LCZ696 over enalapril for the primary endpoint was similar across the spectrum of risk (p = 0.159). Treating 100 patients for 2 years with LCZ696 instead of enalapril led to 7 fewer patients in the highest quintile of risk experiencing primary outcomes, compared with 3 in the lowest quintile. Analyses using the EMPHASIS-HF risk score gave similar findings. CONCLUSIONS: Although most PARADIGM-HF patients had mild symptoms, many were at high risk for adverse outcomes and obtained a large absolute benefit from LCZ696, compared with enalapril, over a relatively short treatment period. LCZ696's benefit was consistent across the spectrum of risk. (PARADIGM-HF trial [Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure]; NCT01035255).
RCT Entities:
BACKGROUND: Although most patients in the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial had mild symptoms, there is a poor correlation between reported functional limitation and prognosis in heart failure. OBJECTIVES: The aim of this study was to examine the spectrum of risk in PARADIGM-HF and the effect of LCZ696 across that spectrum. METHODS: This study analyzed rates of the primary composite outcome of cardiovascular death or heart failure hospitalization, its components, and all-cause mortality using the MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) and EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) risk scores to categorize patients. The authors determined whether risk, on the basis of these scores, modified the treatment effect of LCZ696. RESULTS: The complete MAGGIC risk score was available for 8,375 of the 8,399 patients in PARADIGM-HF. The median MAGGIC score was 20 (IQR: 16 to 24). An increase of 1 point was associated with a 6% increased risk for the primary endpoint (p < 0.001) and a 7% increased risk for cardiovascular death (p < 0.001). The benefit of LCZ696 over enalapril for the primary endpoint was similar across the spectrum of risk (p = 0.159). Treating 100 patients for 2 years with LCZ696 instead of enalapril led to 7 fewer patients in the highest quintile of risk experiencing primary outcomes, compared with 3 in the lowest quintile. Analyses using the EMPHASIS-HF risk score gave similar findings. CONCLUSIONS: Although most PARADIGM-HF patients had mild symptoms, many were at high risk for adverse outcomes and obtained a large absolute benefit from LCZ696, compared with enalapril, over a relatively short treatment period. LCZ696's benefit was consistent across the spectrum of risk. (PARADIGM-HF trial [Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure]; NCT01035255).
Authors: Kishan S Parikh; Steven J Lippmann; Melissa Greiner; Paul A Heidenreich; Clyde W Yancy; Gregg C Fonarow; Adrian F Hernandez Journal: Circulation Date: 2017-05-23 Impact factor: 29.690