A Cohort Study to Compare the Hospitalization Between Naive Sacubitril/Valsartan and Naive ACEi/ARBs Heart Failure Patients With Reduced Ejection Fraction Using Secondary US Electronic Health Records Data

A non-interventional retrospective cohort study conducted to compare the naive sacubitril/valsartan Heart Failure with reduced Ejection Fraction (HFrEF) patient population to a matched naive ACEi/ARB HFrEF patient population.

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Drug: Sacubitril/valsartan; Drug: ACEi/ARB

Detailed Description

This was a non-interventional retrospective cohort study using the US secondary EHR dataset, Optum EHR, to compare the naive sacubitril/valsartan HFrEF patient population (aged ≥ 18 years) to a matched naive ACEi/ARB HFrEF patient population.

The study comprised of the following periods:

Identification period: 01-Jul-2015 to 31-Mar-2019

Study period

• 01-Jul-2014 to 31-Mar-2020 for primary objective and secondary objective 2 to 6.
• 01-Jul-2008 to 30-Sep-2020 for secondary objective 1.

Follow-up period: Patients were followed up until 31-Mar-2020, death or patient transfer out.

Baseline period: 365 days prior to index

• Study Type: Observational
• Enrollment (Actual): 42269

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 81 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The study included heart failure patients with reduced ejection fraction

Description

Inclusion Criteria:

Sacubitril/valsartan incident cohort Included patients

• Prescribed sacubitril/valsartan within the identification period (01-July-2015 to 31-Mar-2019), that had non-missing gender and year of birth data.
• With at least one ICD-9-CM or ICD-10-CM code for diagnosis of HF within one-year prior to date of first prescription of sacubitril/valsartan (index date), and are treated as part of the integrated delivery network.
• With first month active 365 days prior to index and last date active was greater than or equal to (≥) index, and the month of provider source data was greater than the final date of patient follow-up.
• That were ≥18 years old at index date.
• With a valid LVEF value ≤40%, prior to index (index date included).

Angiotensin-converting enzyme inhibitors (ACEi) and Angiotensin II receptor antagonist (ARB) incident cohort

Included patient:

• Prescribed ACEi or ARBs within the identification period (01-Jul-2015 to 31-Mar-2019), that had non-missing gender and year of birth data.
• With at least one ICD-9-CM or ICD-10-CM code for diagnosis of HF within one-year prior to date of first prescription of ACEi or ARB (index date), and were treated as part of the integrated delivery network.
• With first month active 365 days prior to index and last date active was ≥ index, and the month of provider source data is greater than the final date of patient follow-up.
• That were ≥ 18 years old at index date.
• With a valid LVEF value ≤ 40%, prior to index (index date included).

Exclusion Criteria:

Sacubitril/valsartan incident cohort

Excluded patients for the primary objective and secondary objective 2 to 6:

• Patients who were prescribed sacubitril/valsartan within one-year prior to index date.
• Patients who were prescribed ACEi or ARBs, within one-year prior to index date (index date included).

Exclude patients for secondary objective 1:

• Patients who were prescribed sacubitril/valsartan prior to index date.
• Patients who were prescribed ACEi or ARBs prior to index date (index date included).

Angiotensin-converting enzyme inhibitors (ACEi) and Angiotensin II receptor antagonist (ARB) incident cohort

Exclude patients for the primary objective and secondary objective 2 to 6:

• Patients who were prescribed ACEi or ARBs within one-year prior to index date.
• Patients who were prescribed sacubitril/valsartan within one-year prior to index date (index date included).
• Which had a valid sacubitril/valsartan prescription that enables inclusion in the sacubitril/valsartan cohort.
• Exclude patients for secondary objective 1:
• Patients who were prescribed ACEi or ARBs prior to index date.
• Patients who were prescribed sacubitril/valsartan prior to index date (index date included).
• Which had a valid sacubitril/valsartan prescription that enables inclusion in the sacubitril/valsartan cohort

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Naive Sacubitril/valsartan; Participants who were prescribed with Naive Sacubitril/valsartan	Drug: Sacubitril/valsartan; Participants who were prescribed with Sacubitril/valsartan; Other Names: Entresto®
Naive ACEi/ARB; Participants who were prescribed with Naive Angiotensin-converting enzyme inhibitors/Angiotensin II receptor antagonists (ACEi/ARB)	Drug: ACEi/ARB; Participants who were prescribed with Angiotensin-converting enzyme inhibitors/Angiotensin II receptor antagonists (ACEi/ARB)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Heart Failure (HF) hospitalizations events for both Naive sacubitril/valsartan HFrEF patients and Naive ACEi/ARB Heart Failure with reduced Ejection Fraction (HFrEF) patients	Heart failure hospitalizations were defined by ICD-9-CM (The International Classification of Diseases, 9th Revision, Clinical Modification) and ICD-10-CM (International Classification of Diseases, 10th Revision, Clinical Modifier) codes for HF listed within the primary diagnoses associated with a hospitalization that occurred during the follow-up period.	through study completion, maximum 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of HF hospitalizations events for both Truly naive sacubitril/valsartan HFrEF patients and Truly naive ACEi/ARB HFrEF patients	Heart failure hospitalizations were defined by ICD-9-CM (The International Classification of Diseases, 9th Revision, Clinical Modification) and ICD-10-CM (International Classification of Diseases, 10th Revision, Clinical Modifier) codes for HF listed within the primary diagnoses associated with a hospitalization that occurred during the follow-up period.	through study completion, maximum 5 years
Time to first HF hospitalization for both Naive sacubitril/valsartan HFrEF patients and Naive ACEi/ARB HFrEF patients	Heart failure hospitalizations were defined by ICD-9-CM (The International Classification of Diseases, 9th Revision, Clinical Modification) and ICD-10-CM (International Classification of Diseases, 10th Revision, Clinical Modifier) codes for HF listed within the primary diagnoses associated with a hospitalization that occurred during the follow-up period.	through study completion, maximum 5 years
Rate of HF hospitalizations or Emergency room (ER) visits for both Naive sacubitril/valsartan HFrEF patients and Naive ACEi/ARB HFrEF patients	HF ER visits were defined by ICD-9-CM and ICD-10-CM codes for HF listed within the primary diagnoses associated with ER visits that occurred during the follow-up period.	through study completion, maximum 5 years
Time to first HF hospitalization or HF ER visit for both Naive sacubitril/valsartan HFrEF patients and Naive ACEi/ARB HFrEF patients	HF ER visits were defined by ICD-9-CM and ICD-10-CM codes for HF listed within the primary diagnoses associated with ER visits that occurred during the follow-up period.	through study completion, maximum 5 years
Rate of all-cause hospitalizations events between Naive sacubitril/valsartan HFrEF patients and Naive ACEi/ARB HFrEF patients	All-cause hospitalizations were defined as any hospitalization that occurred during the follow-up period.	through study completion, maximum 5 years
Time to first all-cause hospitalizations events between Naive sacubitril/valsartan HFrEF patients and Naive ACEi/ARB HFrEF patients	All-cause hospitalizations were defined as any hospitalization that occurred during the follow-up period.	through study completion, maximum 5 years
Rates of cardiovascular hospitalization events between Naive sacubitril/valsartan HFrEF patients and Naive ACEi/ARB HFrEF patients	The rate of cardiovascular hospitalization events between Naive sacubitril/valsartan HFrEF patients and Naive ACEi/ARB HFrEF patients was reported	through study completion, maximum 5 years

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for CLCZ696B2036 from the Novartis Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2020
• Primary Completion (Actual): October 19, 2020
• Study Completion (Actual): October 19, 2020

Study Registration Dates

• First Submitted: October 19, 2021
• First Submitted That Met QC Criteria: October 19, 2021
• First Posted (Actual): October 27, 2021

Study Record Updates

• Last Update Posted (Actual): December 21, 2021
• Last Update Submitted That Met QC Criteria: December 15, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: electronic health record; Heart failure hospitalizations,; sacubitril/valsartan,; Angiotensin II receptor antagonist,; United States,
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Valsartan; Sacubitril and valsartan sodium hydrate drug combination
• Other Study ID Numbers: CLCZ696B2036

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No