Angiotensin receptor neprilysin inhibition compared with enalapril on the risk of clinical progression in surviving patients with heart failure.
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McMurray, John J V
Desai, Akshay S
Lefkowitz, Martin P
Rizkala, Adel R
Rouleau, Jean L
Shi, Victor C
Solomon, Scott D
Arango, Juan Luis
Arnold, J Malcolm
Burgess, Lesley J
Duarte, Yan Carlos
Hagège, Albert A
Llamas, Edmundo Bayram
Ramires, Felix J A
Sibulo, Antonio S
Squire, Iain B
Starling, Randall C
Teerlink, John R
Wong, Raymond Ching-Chiew
MetadataShow full item record
CitationCirculation 2015, 131 (1):54-61
AbstractClinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk of clinical deterioration in surviving patients.
We compared the angiotensin-neprilysin inhibitor LCZ696 (400 mg daily) with the angiotensin-converting enzyme inhibitor enalapril (20 mg daily) in 8399 patients with heart failure and reduced ejection fraction in a double-blind trial. The analyses focused on prespecified measures of nonfatal clinical deterioration. In comparison with the enalapril group, fewer LCZ696-treated patients required intensification of medical treatment for heart failure (520 versus 604; hazard ratio, 0.84; 95% confidence interval, 0.74-0.94; P=0.003) or an emergency department visit for worsening heart failure (hazard ratio, 0.66; 95% confidence interval, 0.52-0.85; P=0.001). The patients in the LCZ696 group had 23% fewer hospitalizations for worsening heart failure (851 versus 1079; P<0.001) and were less likely to require intensive care (768 versus 879; 18% rate reduction, P=0.005), to receive intravenous positive inotropic agents (31% risk reduction, P<0.001), and to have implantation of a heart failure device or cardiac transplantation (22% risk reduction, P=0.07). The reduction in heart failure hospitalization with LCZ696 was evident within the first 30 days after randomization. Worsening of symptom scores in surviving patients was consistently more common in the enalapril group. LCZ696 led to an early and sustained reduction in biomarkers of myocardial wall stress and injury (N-terminal pro-B-type natriuretic peptide and troponin) versus enalapril.
Angiotensin-neprilysin inhibition prevents the clinical progression of surviving patients with heart failure more effectively than angiotensin-converting enzyme inhibition.
http://www.clinicaltrials.gov. Unique identifier: NCT01035255.
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RightsArchived with thanks to Circulation
- Angiotensin-neprilysin inhibition versus enalapril in heart failure.
- Authors: McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR, PARADIGM-HF Investigators and Committees.
- Issue date: 2014 Sep 11
- Factors Associated With Noncompletion During the Run-In Period Before Randomization and Influence on the Estimated Benefit of LCZ696 in the PARADIGM-HF Trial.
- Authors: Desai AS, Solomon S, Claggett B, McMurray JJ, Rouleau J, Swedberg K, Zile M, Lefkowitz M, Shi V, Packer M
- Issue date: 2016 Jun
- Influence of Ejection Fraction on Outcomes and Efficacy of Sacubitril/Valsartan (LCZ696) in Heart Failure with Reduced Ejection Fraction: The Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) Trial.
- Authors: Solomon SD, Claggett B, Desai AS, Packer M, Zile M, Swedberg K, Rouleau JL, Shi VC, Starling RC, Kozan Ö, Dukat A, Lefkowitz MP, McMurray JJ
- Issue date: 2016 Mar
- Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure: rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF).
- Authors: McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau J, Shi VC, Solomon SD, Swedberg K, Zile MR, PARADIGM-HF Committees and Investigators.
- Issue date: 2013 Sep
- Elevation in high-sensitivity troponin T in heart failure and preserved ejection fraction and influence of treatment with the angiotensin receptor neprilysin inhibitor LCZ696.
- Authors: Jhund PS, Claggett BL, Voors AA, Zile MR, Packer M, Pieske BM, Kraigher-Krainer E, Shah AM, Prescott MF, Shi V, Lefkowitz M, McMurray JJ, Solomon SD, PARAMOUNT Investigators.
- Issue date: 2014 Nov