Abstract | Importance: The addition of receptor- neprilysin inhibition to standard therapy, including a renin-angiotensin system blocker, has been demonstrated to improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF) compared with standard therapy alone. The long-term absolute risk reduction from angiotensin receptor neprilysin inhibitor (ARNI) therapy, and whether it merits widespread use among diverse subpopulations, has not been well described. Objective: To calculate estimated 5-year number needed to treat (NNT) values overall and for different subpopulations for the Prospective Comparison of ARNI with Angiotensin-Converting Enzyme Inhibitor (ACEI) to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) cohort. Design, Setting, and Participants: Overall and subpopulation 5-year NNT values were estimated for different end points using data from PARADIGM-HF, a double-blind, randomized trial of sacubitril-valsartan vs enalapril. This multicenter, international study included 8399 men and women with HFrEF (ejection fraction, ≤40%). The study began in December 2009 and ended in March 2014. Analyses began in March 2018. Interventions: Main Outcomes and Measures: Cardiovascular death or HF hospitalization, cardiovascular death, and all-cause mortality. Results: The final cohort of 8399 individuals included 1832 women (21.8%) and 5544 white individuals (66.0%), with a mean (SD) age of 63.8 (11.4) years. The 5-year estimated NNT for the primary outcome of cardiovascular death or HF hospitalization with ARNI therapy incremental to ACEI therapy in the overall cohort was 14. The 5-year estimated NNT values were calculated for different clinically relevant subpopulations and ranged from 12 to 19. The 5-year estimated NNT for all-cause mortality in the overall cohort with ARNI incremental to ACEI was 21, with values ranging from 16 to 31 among different subgroups. Compared with imputed placebo, the 5-year estimated NNT for all-cause mortality with ARNI was 11. The 5-year estimated NNT values were also calculated for other HFrEF therapies compared with controls from landmark trials for all-cause mortality and were found to be 18 for ACEI, 24 for angiotensin receptor blockers, 8 for β-blockers, 15 for mineralocorticoid antagonists, 14 for implantable cardioverter defibrillator, and 14 for cardiac resynchronization therapy. Conclusions and Relevance: The 5-year estimated NNT with ARNI therapy incremental to ACEI therapy overall and for clinically relevant subpopulations of patients with HFrEF are comparable with those for well-established HF therapeutics. These data further support guideline recommendations for use of ARNI therapy among eligible patients with HFrEF.
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Authors | Pratyaksh K Srivastava, Brian L Claggett, Scott D Solomon, John J V McMurray, Milton Packer, Michael R Zile, Akshay S Desai, Jean L Rouleau, Karl Swedberg, Gregg C Fonarow |
Journal | JAMA cardiology
(JAMA Cardiol)
Vol. 3
Issue 12
Pg. 1226-1231
(12 01 2018)
ISSN: 2380-6591 [Electronic] United States |
PMID | 30484837
(Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Aminobutyrates
- Angiotensin Receptor Antagonists
- Angiotensin-Converting Enzyme Inhibitors
- Biphenyl Compounds
- Drug Combinations
- Tetrazoles
- Enalapril
- Valsartan
- Neprilysin
- sacubitril and valsartan sodium hydrate drug combination
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Topics |
- Aged
- Aminobutyrates
(therapeutic use)
- Angiotensin Receptor Antagonists
(therapeutic use)
- Angiotensin-Converting Enzyme Inhibitors
(therapeutic use)
- Biphenyl Compounds
- Cause of Death
(trends)
- Double-Blind Method
- Drug Combinations
- Enalapril
(therapeutic use)
- Female
- Follow-Up Studies
- Heart Arrest
(epidemiology, prevention & control)
- Heart Failure
(drug therapy, mortality, physiopathology)
- Hospitalization
(trends)
- Humans
- Male
- Middle Aged
- Neprilysin
(antagonists & inhibitors)
- Prognosis
- Prospective Studies
- Quebec
(epidemiology)
- Stroke Volume
(physiology)
- Survival Rate
(trends)
- Sweden
(epidemiology)
- Tetrazoles
(therapeutic use)
- Time Factors
- United Kingdom
(epidemiology)
- United States
(epidemiology)
- Valsartan
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