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Angiotensin receptor neprilysin inhibition compared with enalapril on the risk of clinical progression in surviving patients with heart failure
Packer, Milton McMurray, John J. V. Desai, Akshay S. Gong, Jianjian Lefkowitz, Martin P. Rizkala, Adel R. Rouleau, Jean L. Shi, Victor C. Solomon, Scott D. Swedberg, Karl
Packer, Milton
McMurray, John J. V.
Desai, Akshay S.
Gong, Jianjian
Lefkowitz, Martin P.
Rizkala, Adel R.
Rouleau, Jean L.
Shi, Victor C.
Solomon, Scott D.
Swedberg, Karl
Author
Packer, Milton
McMurray, John J. V.
Desai, Akshay S.
Gong, Jianjian
Lefkowitz, Martin P.
Rizkala, Adel R.
Rouleau, Jean L.
Shi, Victor C.
Solomon, Scott D.
Swedberg, Karl
Zile, Michael R.
Andersen, Karl
Arango, Juan Luis
Arnold, J. Malcolm
Belohlávek, Jan
Bohm, Michael
Boytsov, Sergey
Burgess, Lesley J.
Cabrera, Walter
Calvo, Carlos
Chen, -Huan Chen
Dukat, Andrej
Duarte, Yan Carlos
Erglis, Andrejs
Fu, Michael
Gomez, Efrain
Gonzàlez-Medina, Angel
Hagege, Albert Alain
Huang, Jun
Katova, Tzventana
Kiatchoosakun, Songsak
Kim, Kee-Sik
Kozan, Ömer
Llamas, Edmundo Bayram
Martinez, Felipe
Merkely, Bela
Mendoza, Iván
Mosterd, Arend
Negrusz-Kawecka, Marta
Peuhkurinen, Keijo
Ramires, Felix J. A.
Refsgaard, Jens
Rosenthal, Arvo
Senni, Michele
Sibulo, Antonio S.
Silva-Cardoso, José
Squire, Iain B.
Starling, Randall C.
Teerlink, John R.
Vanhaecke, Johan
Vinereanu, Dragos
Wong, Raymond Ching-Chiew
McMurray, John J. V.
Desai, Akshay S.
Gong, Jianjian
Lefkowitz, Martin P.
Rizkala, Adel R.
Rouleau, Jean L.
Shi, Victor C.
Solomon, Scott D.
Swedberg, Karl
Zile, Michael R.
Andersen, Karl
Arango, Juan Luis
Arnold, J. Malcolm
Belohlávek, Jan
Bohm, Michael
Boytsov, Sergey
Burgess, Lesley J.
Cabrera, Walter
Calvo, Carlos
Chen, -Huan Chen
Dukat, Andrej
Duarte, Yan Carlos
Erglis, Andrejs
Fu, Michael
Gomez, Efrain
Gonzàlez-Medina, Angel
Hagege, Albert Alain
Huang, Jun
Katova, Tzventana
Kiatchoosakun, Songsak
Kim, Kee-Sik
Kozan, Ömer
Llamas, Edmundo Bayram
Martinez, Felipe
Merkely, Bela
Mendoza, Iván
Mosterd, Arend
Negrusz-Kawecka, Marta
Peuhkurinen, Keijo
Ramires, Felix J. A.
Refsgaard, Jens
Rosenthal, Arvo
Senni, Michele
Sibulo, Antonio S.
Silva-Cardoso, José
Squire, Iain B.
Starling, Randall C.
Teerlink, John R.
Vanhaecke, Johan
Vinereanu, Dragos
Wong, Raymond Ching-Chiew
Abstract
Background: Clinical 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. Methods and Results: 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. Conclusions: Angiotensin-neprilysin inhibition prevents the clinical progression of surviving patients with heart failure more effectively than angiotensin-converting enzyme inhibition.
Keywords
heart failure, neprilysin, receptors, angiotensin
Date
2015
Type
Journal article
Journal
Circulation
Book
Volume
131
Issue
1
Page Range
54-61
Article Number
ACU Department
Collections
Relation URI
Source URL
Event URL
Open Access Status
Open access
License
File Access
Controlled