Effectiveness of Entresto (Sacubitril/Valsartan) in Japanese Patients With Hypertension

Effectiveness of Entresto (Sacubitril/Valsartan) to Blood Pressure Control in Japanese Patients With Hypertension: the Database Analysis of Electronic Medical Records

This study is a non-interventional, secondary use of data, retrospective, cohort study, and the data to be extracted in this study will be used as secondary use of collected patient information in the database (Japan Medical Data Survey [JAMDAS]) owned by M3 Inc. JAMDAS is a database that aggregates medical information and is constructed mainly from electronic medical record information of general practices, allowing real-time extraction of information entered in medical records, such as prescription status including drug switching and continuation, laboratory values, clinical evaluation scores, and comorbidities, etc.

Study Overview

• Status: Active, not recruiting
• Conditions: Essential Hypertension

• Study Type: Observational
• Enrollment (Actual): 1405

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: N/A

• Sampling Method: Non-Probability Sample

Study Population

This is a retrospective, noninterventional cohort study.

Description

Inclusion criteria:

1. Diagnosed with essential hypertension (International Classification of Diseases [ICD]-10 code: I10) on the index date.
2. Patients for whom data for the 6 months prior to the index date can be extracted as baseline data.
3. Patients for whom blood pressure (BP) data can be extracted between weeks 8 and 12 after the index date.
4. Patients whose BP data can be extracted on the index date.
5. Patients whose BP value at baseline was 140/90 millimeters of mercury (mmHg) or higher.
6. Patients with the prescription of 100 milligrams (mg) or 200 mg once daily as 100 mg or 200 mg tablets on the index date.

Exclusion criteria:

1. Women with a record of pregnancy-related diagnoses, drugs, or medical procedures before or after the index date, or a record of delivery- or abortion-related diagnoses, drugs, or medical procedures after the index date.
2. Prescription of concomitant angiotensin-converting enzyme inhibitor (ACEi); Anatomical Therapeutic Chemical (ATC) code: C09A on, after, or in the 2 days before the index date.
3. Patients diagnosed with angioedema: ICD-10: D84.1 under prescription of ACEi or angiotensin receptor blocker (ARB); ATC code: C09C.
4. Patients diagnosed with diabetes and under treatment with aliskiren fumarate on the index date.
5. Patients with severe impaired liver functions with Child-Pugh classification C.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Sacubitril/Valsartan Cohort; Adult patients with essential hypertension who were prescribed sacubitril/valsartan.
Conventional Drug-control Cohort; Adult patients with essential hypertension who were prescribed angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Achieving the Guideline-recommended Blood Pressure (BP)	The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019) will be used to establish systolic and diastolic blood pressure goals.	Up to approximately 12 weeks (the BP measurement timepoint closest to 8 weeks between weeks 8 and 12)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Height		Baseline
Weight		Baseline
Percentage of Patients Achieving the Guideline-recommended Blood Pressure (BP) per BP Category	The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019) will be used to establish systolic and diastolic blood pressure goals. BP categories: Grade I: 140-159/90-99 millimeters of mercury (mmHg); Grade II: 160-179/100-109 mmHg; Grade III: 180/110 mmHg or greater	Up to approximately 12 weeks (the BP measurement timepoint closest to 8 weeks between weeks 8 and 12)
Percentage of Patients Achieving the Guideline-recommended BP Categorized by Number of Antihypertensive Medicines Taken Before Starting Sacubitril/Valsartan	The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019) will be used to establish systolic and diastolic blood pressure goals. Number of antihypertensive medicines taken before starting sacubitril/valsartan categories: 0, 1, 2, 3-4, and 5 or more.	Up to approximately 12 weeks (the BP measurement timepoint closest to 8 weeks between weeks 8 and 12)
Percentage of Patients Achieving the Guideline-recommended BP Categorized by Antihypertensive Drug Classes Prescribed With Sacubitril/Valsartan	The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019) will be used to establish systolic and diastolic blood pressure goals. Antihypertensive drug classes include: Calcium channel blockers (CCB); Angiotensin-converting enzyme (ACE) inhibitors; Angiotensin receptor blockers (ARBs); Diuretics; Alpha and beta blockers; Alpha-beta blockers; Aldosterone blockers; Renin inhibitors; Compounding agents	Up to approximately 12 weeks (the BP measurement timepoint closest to 8 weeks between weeks 8 and 12)
Percentage of Patients Achieving the Guideline-recommended BP Categorized by Patient Characteristics	The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019) will be used to establish systolic and diastolic blood pressure goals. Patient characteristics include, but are not limited to, age, gender, body mass index (BMI), comorbidities, and combinations of comorbidities.	Up to approximately 12 weeks (the BP measurement timepoint closest to 8 weeks between weeks 8 and 12)
Number of Patients Categorized by Place of Residence		Baseline
Number of Patients Categorized by Comorbidities	Comorbidities include: Heart disease; Diabetes; Dyslipidemia; Renal disease; Cerebrovascular disease; Other, specify	Baseline
Relative Contribution of Baseline Characteristics in Achieving the Guideline-recommended BP	The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019) will be used to establish systolic and diastolic blood pressure goals. Multivariate logistic regression analysis will be used to determine the association of the following variables in achieving the guideline-recommended BP.; Age; Gender; Comorbidities; Body mass index (BMI); BP category at index date; Number of classes of antihypertensive medicines taken before starting sacubitril/valsartan	Up to approximately 12 weeks (the BP measurement timepoint closest to 8 weeks between weeks 8 and 12)
Persistence on Sacubitril/Valsartan	Proportion of patients remaining on treatment with sacubitril/valsartan and proportion of patients permanently discontinuing sacubitril/valsartan during the study.	Up to 16 weeks
Number of Episodes of Hypotension-related Events	Hypotension-related events include: Orthostatic hypotension; Postural hypotension; Secondary orthostatic hypotension; Hypertension due to the drugs; Episodic hypotension; Hypotension; Vertigo; Feeling dizzy; Dizziness; Sudden dizziness; Syncope	Up to 16 weeks
Number of Episodes of Renal Events	Renal events include: Renal diseases; Chronic kidney disease (CKD); Estimated glomerular filtration rate (eGFR) reduction of 40% or more	Up to 16 weeks
Number of Episodes of Dehydration-related Events	Dehydration-related events include: Dehydration; Isotonic dehydration	Up to 16 weeks
Number of Episodes of Diuresis-related Events	Diuresis-related events include: Polyuria; Idiopathic polyuria; Frequent urination; Nocturnal polyuria; Nocturia	Up to 16 weeks
Number of Episodes of Edema or Angioedema-related Events	Edema or angioedema-related events include: Angioneurotic edema; Quincke's edema	Up to 16 weeks
Percentage of Patients Treated With Sacubitril/Valsartan Achieving the Guideline-recommended BP Compared to the Percentage of Patients Treated With Angiotensin-converting Enzyme Inhibitor/Angiotensin Receptor Blocker (ACEi/ARB)	The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019) will be used to establish systolic and diastolic blood pressure goals.	Up to approximately 12 weeks (the BP measurement timepoint closest to 8 weeks between weeks 8 and 12)

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2023
• Primary Completion (Estimated): March 31, 2025
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: September 17, 2024
• First Submitted That Met QC Criteria: September 17, 2024
• First Posted (Actual): September 20, 2024

Study Record Updates

• Last Update Posted (Actual): September 20, 2024
• Last Update Submitted That Met QC Criteria: September 17, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Essential Hypertension
• Other Study ID Numbers: CLCZ696AJP04