Comparative Effectiveness of Entresto (Sacubitril/Valsartan) Versus ACEi/ARB in de Novo Heart Failure Patients

This was a non-interventional retrospective cohort study of de novo heart failure with reduced ejection fraction (HFrEF) patients (aged ≥18 years) commencing first-line treatment on either sacubitril/valsartan or commencing or continuing angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blocker (ARB) therapy for HF in the United States (US) using the secondary source of data, Optum Electronic Health Records (EHR).

Study Overview

• Status: Completed
• Conditions: de Novo Heart Failure

• Study Type: Observational
• Enrollment (Actual): 9870

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • East Hanover, New Jersey, United States, 07936
      • Novartis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This was a retrospective, noninterventional cohort study

Description

Inclusion Criteria:

Sacubitril/valsartan cohort:

• Prescribed sacubitril/valsartan within the identification period.
• With at least one International Classification of Diseases, 9th Revision (ICD)-9 or 10th Revision (ICD-10) code for diagnosis of HF within 30 days prior to the index date (including index date), that had non-missing sex and year of birth data.
• Active in the database for 759 days prior to index.
• With left ventricular ejection fraction (LVEF) ≤ 40% known prior to index day (including index date).
• That were treated as part of the integrated delivery network (IDN).

ACEi/ARB cohort:

• Prescribed ACEi or ARB within the identification period.
• With at least one ICD-9 or ICD-10 code for diagnosis of HF within 30 days prior to the index date (including index date), that have non-missing sex and year of birth data.
• Active in the database for 759 days prior to index.
• With LVEF ≤ 40% known prior to index day (including index date).
• That were treated as part of the IDN.

Exclusion Criteria

Sacubitril/valsartan cohort:

• That were < 18 years old at index date.
• That were prescribed sacubitril/valsartan within the baseline period or identification period (whichever was earlier) at any time prior to the index date (excluding).
• With one or more ICD-9 or ICD-10 codes for diagnosis of HF within the baseline period, excluding the 30 days prior to index in which HF was initially identified (patient should have had no prior history of HF).
• That were prescribed ACEi/ARB > 2 days before index date, and within 30 days after a HF diagnosis during the identification period (i.e. any patient included in the ACEi/ARB cohort with an earlier index date, regardless of whether LVEF was ≤ 40% or > 40%)
• With LVEF ≤ 10% as the closest value to index date (including).

ACEi/ARB cohort:

• That were < 18 years old at index date.
• That were prescribed sacubitril/valsartan within the baseline period or identification period (whichever was earlier) at any time prior to the index date, on the index date, or until ≤ 2 days after the index date.
• With one or more ICD-9 or ICD-10 codes for diagnosis of HF within the baseline period, excluding the 30 days prior to index in which HF was initially identified (patient should have had no prior history of HF).
• With LVEF ≤ 10% as the closest value to index date (including).

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Sacubitril/valsartan; Prescribed sacubitril/valsartan
ACEi/ARB; Prescribed ACEi or ARB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Total number of all-cause hospitalizations	Up to approximately 5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to first all-cause hospitalization	Up to approximately 5 years
Number and proportion of HF-specific inpatient hospitalizations	Up to approximately 5 years
Number and proportion of HF-related inpatient hospitalizations	Up to approximately 5 years
Number and proportion of cardiovascular (CV)-specific inpatient hospitalizations	Up to approximately 5 years
Numbers and proportions of first and recurrent (1st, 2nd, 3rd, 4th and 5th) all-cause inpatient hospitalizations	Up to approximately 5 years
Numbers and proportions of first and recurrent (1st, 2nd, 3rd, 4th and 5th) HF-specific inpatient hospitalizations.	Up to approximately 5 years
Number and proportion of patients with ≥1 implantable cardioverter defibrillator (ICD) insertion during a hospitalization or during an emergency room (ER) visit for both the sacubitril/valsartan and ACEi/ARB cohorts	Up to approximately 5 years
Number and proportion of non-HF inpatient hospitalizations	Up to approximately 5 years
Number and proportion of non-CV inpatient hospitalizations	Up to approximately 5 years
Dosages and dose changes of sacubitril/valsartan administered	Up to approximately 5 years

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2021
• Primary Completion (Actual): July 19, 2022
• Study Completion (Actual): July 19, 2022

Study Registration Dates

• First Submitted: July 19, 2023
• First Submitted That Met QC Criteria: July 19, 2023
• First Posted (Actual): July 27, 2023

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 19, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: CLCZ696B2037