Angiotensin receptor neprilysin inhibition compared with enalapril on the risk of clinical progression in surviving patients with heart failure.
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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, Andersen Karl, Arango Juan Luis, Arnold J Malcolm, Bělohlávek Jan, Böhm Michael, Boytsov Sergey, Burgess Lesley J, Cabrera Walter, Calvo Carlos, Chen Chen-Huan, Dukat Andrej, Duarte Yan Carlos, Erglis Andrejs, Fu Michael, Gomez Efrain, Gonzàlez-Medina Angel, Hagège Albert A, Huang Jun, Katova Tzvetana, 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, PARADIGM-HF Investigators and Coordinators
Аннотация
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.
CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255.