6533b7d3fe1ef96bd1260a6f
RESEARCH PRODUCT
Angiotensin Receptor Neprilysin Inhibition Compared With Enalapril on the Risk of Clinical Progression in Surviving Patients With Heart Failure
Milton PackerJohn J. V. McmurrayAkshay S. DesaiJianjian GongMartin P. LefkowitzAdel R. RizkalaJean L. RouleauVictor C. ShiScott D. SolomonKarl SwedbergMichael ZileKarl AndersenJuan Luis ArangoJ. Malcolm ArnoldJan BelohlávekMichael BöhmSergey BoytsovLesley J. BurgessWalter CabreraCarlos CalvoChen Huan ChenAndrej DukatYan Carlos DuarteAndrejs ErglisFu MichaelEfrain GomezAngel Gonzàlez MedinaAlbert A. HagègeJun HuangTzvetana KatovaSongsak KiatchoosakunKee Sik KimÖMer KozanEdmundo Bayram LlamasFelipe MartinezBela MerkelyIván MendozaArend MosterdMarta Negrusz KaweckaKeijo PeuhkurinenFelix J. A. RamiresJens RefsgaardArvo RosenthalMichele SenniAntonio S. SibuloJosé Silva CardosoIain B. SquireRandall C. StarlingJohn R. TeerlinkJohan VanhaeckeDragos VinereanuRaymond Ching Chiew Wong Paradigm Hf Investigators CoordinatorsGiuseppe Lembosubject
Angiotensin receptorVascular damage Radboud Institute for Health Sciences [Radboudumc 16]receptorsTetrazolesheart failureAngiotensin-Converting Enzyme InhibitorsKaplan-Meier EstimateSacubitrilAngiotensin; Heart failure; Neprilysin; Receptors; Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biomarkers; Double-Blind Method; Enalapril; Heart Failure; Humans; Kaplan-Meier Estimate; Natriuretic Peptide Brain; Neprilysin; Peptide Fragments; Risk Factors; Stroke Volume; Survivors; Tetrazoles; Treatment Outcome; Troponin; Disease Progression; Medicine (all); Cardiology and Cardiovascular Medicine; Physiology (medical)AngiotensinEnalaprilRisk FactorsEnalapril/therapeutic useNatriuretic Peptide BrainHeart Failure/bloodSurvivorsReceptorNeprilysinAminobutyrates: Systèmes cardiovasculaire & respiratoire [D03] [Sciences de la santé humaine]Troponin/bloodTroponinAngiotensin Receptor Antagonists/therapeutic useDrug CombinationsAngiotensin-Converting Enzyme Inhibitors/therapeutic useTreatment OutcomeTetrazoles/therapeutic useCardiologyDisease ProgressionValsartanNeprilysinHeart Failure/blood/drug therapy/physiopathologyCardiology and Cardiovascular Medicinemedicine.drugReceptormedicine.medical_specialtyHeart failureneprilysinAngiotensin Receptor Antagonistsreceptors angiotensinDouble-Blind MethodPhysiology (medical)Internal medicineRenin–angiotensin systemmedicineHumansheart failure neprilysin receptors angiotensinEnalaprilbusiness.industryBiphenyl CompoundsStroke Volumemedicine.diseasePeptide FragmentsEndocrinologyAminobutyrates/therapeutic useStroke Volume/physiologyHeart failureNatriuretic Peptide Brain/blood: Cardiovascular & respiratory systems [D03] [Human health sciences]businessNeprilysin/antagonists & inhibitorsPeptide Fragments/bloodSacubitril ValsartanBiomarkersBiomarkers/blooddescription
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. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01035255.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-01-06 |