# PARADIGM-HF

Study · id `cardio:paradigm-hf` · Cardiovascular Atlas · release `5dcd9b263fe17744` (public)

> General information from published sources, not medical advice, and not reviewed by clinicians. Check the cited source before relying on anything here.

The atlas's own text and curation may be reused under Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0, https://creativecommons.org/licenses/by-nc/4.0/): credit the atlas, and do not use it commercially. See the atlas About page. Text quoted from a source stays under that source's own terms, given as the source's reuse\_basis. The atlas's reuse terms do not cover it. The downloads list each quotation with its source in third\_party\_quotations.

Also called: LCZ696 versus enalapril in heart failure trial

Browse, organ or system: Heart  
Browse, condition area: Heart failure  

## In plain language

A large trial in adults with heart failure and a reduced ejection fraction (40% or less). It compared LCZ696, a combination of sacubitril and valsartan, with enalapril, an ACE inhibitor, each added to recommended treatment. The trial was stopped early, because the prespecified boundary for overwhelming benefit with LCZ696 was crossed. Fewer people on LCZ696 died from cardiovascular causes or were admitted to hospital for heart failure. Low blood pressure and nonserious angioedema were more common with LCZ696.

## Technical summary

Novartis-sponsored, randomized, double-blind, active-controlled phase 3 trial (NCT01035255) of 8442 patients with NYHA class II to IV heart failure and an ejection fraction of 40% or less. Stopped early after a median follow-up of 27 months. Primary outcome: cardiovascular death or hospitalization for heart failure in 914 patients (21.8%) with LCZ696 and 1117 (26.5%) with enalapril, hazard ratio 0.80 (95% CI 0.73 to 0.87), from the PubMed abstract. The PubMed record indexes LCZ696 as the sacubitril and valsartan drug combination. The registry status is terminated and the registry gives no start-date type. The full text was not read. Funding is stated in the abstract as Novartis. The registry lists Novartis Pharmaceuticals as lead sponsor, and this record links to the Novartis organization record.

## Key facts

- Design: Randomized, parallel-group, double-blind, active-controlled phase 3 trial comparing LCZ696 200 mg twice daily with enalapril 10 mg twice daily, each added to recommended therapy. The registry records masking as double and describes a single-blind run-in period before randomization.
- Phase: Phase 3
- Enrolled: 8442 patients (randomized count; Angiotensin-neprilysin inhibition versus enalapril in heart failure, snapshot `cardio:pubmed-25176015-2026-10-14`, retrieved 2026-10-14)
- Started: 2009-12 (This Study Will Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure, snapshot `cardio:ctgov-nct01035255-2026-10-14`, retrieved 2026-10-14)
- Primary completion: 2014-05 (actual) (This Study Will Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure, snapshot `cardio:ctgov-nct01035255-2026-10-14`, retrieved 2026-10-14)
- Completion: 2014-05 (actual) (This Study Will Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure, snapshot `cardio:ctgov-nct01035255-2026-10-14`, retrieved 2026-10-14)
- Results first posted: 2015-09-07 (This Study Will Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure, snapshot `cardio:ctgov-nct01035255-2026-10-14`, retrieved 2026-10-14)
- Countries: United States; Argentina; Belgium; Brazil; Bulgaria; Canada; Chile; China; Colombia; Czechia; Denmark; Dominican Republic; Ecuador; Estonia; Finland; France; Germany; Guatemala; Hungary; Iceland; India; Israel; Italy; Latvia; Lithuania; Malaysia; Mexico; Netherlands; Panama; Peru; Philippines; Poland; Portugal; Romania; Russia; Singapore; Slovakia; South Africa; South Korea; Spain; Sweden; Taiwan; Thailand; United Kingdom; Venezuela; Hong Kong SAR China; Türkiye (This Study Will Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure, snapshot `cardio:ctgov-nct01035255-2026-10-14`, retrieved 2026-10-14)
- Care setting: Not reported
- Registry status: "TERMINATED" (U.S. National Library of Medicine (ClinicalTrials.gov), snapshot `cardio:ctgov-nct01035255-2026-10-14`, retrieved 2026-10-14)
- Stopped early: The trial stopped early, date not reported. The abstract says the trial was stopped early, under prespecified rules and after a median follow-up of 27 months, because the boundary for overwhelming benefit with LCZ696 had been crossed. The registry records the status as terminated and gives the same reason, after a final prespecified interim analysis on 28 March 2014. (Angiotensin-neprilysin inhibition versus enalapril in heart failure, snapshot `cardio:pubmed-25176015-2026-10-14`, retrieved 2026-10-14)

## Connected pages

- Tests LCZ696, which the PubMed record indexes as the sacubitril and valsartan drug combination: Sacubitril/valsartan (combination) (`cardio:sacubitril-valsartan`)
- Studies people with this condition: Heart failure with reduced ejection fraction (HFrEF) (`cardio:hfref`)
- Lead sponsor on the registry record: Novartis (`cardio:novartis`)

## Provenance

Content hash: 8f35e30813b77578c7076affad517bfd7ac4ce30ff4c1d8dbef566ee0b2c0226
Last substantive edit: 2026-10-14
Evidence last checked: 2026-10-14