Early Treatment of ARNI on Myocardial Remodeling and Progress

Overview

Myocardial remodeling following myocardial infarction (MI) is an important prognostic factor for heart function and adverse cardiovascular events, especially are intimately linked with heart failure. MI often causes deleterious changes in ventricular size, shape, and function. This adverse remodeling and progress is mediated by neurohormonal and hemodynamic alterations. The angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan was shown to be superior to an ACE inhibitor in patients with heart failure with reduced ejection fraction (HF-REF), reduce the risk of both death (from cardiovascular and all-causes) and heart failure hospitalization, may be a new approach to the treatment of heart failure. However, the impact of early treatment of ARNI on myocardial remodeling and progress, and aerobic exercise capacity in patients with prior MI has yet to be assessed. The aim of this study is to evaluate the efficacy and the safety of early treatment of ARNI on myocardial remodeling and progress, and aerobic exercise capacity in patients following MI.

Full Title of Study: “Early Treatment of ARNI on Myocardial Remodeling and Progress in Patients With Post-AMI (EARLYmyo-CRPⅠ)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: May 1, 2021

Detailed Description

Myocardial remodeling following myocardial infarction (MI) is an important prognostic factor for heart function and adverse cardiovascular events. The angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan was shown to reduce the risk of both death (from cardiovascular and all-causes) and heart failure hospitalization. However, whether early treatment of ARNI following post-MI could alter myocardial remodeling or aerobic exercise capacity has yet to be assessed. The patients with MI within one month were enrolled in the treatment of ARNI group or ACEI group. The study proposes to perform serial Cardiopulmonary Exercise Tests (CPET) to prospectively measure changes in aerobic exercise capacity in patients with prior myocardial infarction (MI), echocardiographic measures of LV end-diastolic/ systolic volumes, LV ejection fraction (LVEF), BNP and protein plasma levels, symptomatic heart failure, and life quality.

Interventions

  • Drug: sacubitril/valsartan
    • sacubitril/valsartan will be applied from 25mg/b.i.d for 1-2 weeks,50mg b.i.d for 2 weeks, to target dosage 100mg b.i.d for 3 months unless severe safety outcome occurs
  • Drug: perindopril
    • Drug: perindopril will be applied from 2mg for q.d for 1-2 weeks, 4mg q.d 2 weeks, to target dosage 8mg q.d for 3 months unless severe safety outcome occur
  • Other: Cardiopulmonary Exercise Test
    • All patients will undergo a first CPET prior to initiation of treatment, a second one after 3 months, and a third one after 6 months of treatment.
  • Other: Echocardiogram
    • An echocardiogram (ultrasound of the heart) will be performed prior to initiation of treatment and then again 3 months, 6 months later.

Arms, Groups and Cohorts

  • Experimental: Experimental: sacubitril/valsartan
    • sacubitril/valsartan will be applied from 25mg b.i.d to 100mg b.i.d. for 3 months
  • Active Comparator: Active Comparator: perindopril
    • perindopril will be applied from 2mg q.d, to 8mg q.d for 3 months

Clinical Trial Outcome Measures

Primary Measures

  • Peak oxygen consumption (VO2)/kg
    • Time Frame: 3 months
    • Difference in the interval change from baseline in peak VO2/kg at 3 months following sacubitril/valsartan from 25mg/b.i.d, 50mg b.i.d, to target dosage 100mg b.i.d for 3 months, when compared with the interval change in perindopril from 2mg q.d, 4mg q.d, to target dosage 8mg q.d for 3 months.
  • Peak Oxygen Pulse (O2-Pulse)
    • Time Frame: 3 months
    • Difference in the interval change from baseline in peak O2-Pulse at 3 months following sacubitril/valsartan or perindopril.
  • LVEF
    • Time Frame: 3 months
    • Difference in the interval changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV) by echocardiography assessment at 3 months, comparing sacubitril/valsartan with perindopril.

Secondary Measures

  • Peak VO2/kg change
    • Time Frame: 6 months
    • Difference in the interval changes from baseline and 6 months in peak VO2 comparing sacubitril/valsartan with perindopril.
  • Peak Oxygen Pulse change
    • Time Frame: 6 months
    • Difference in the interval changes from baseline and 6 months in peak O2-Pulse comparing sacubitril/valsartan with perindopril.
  • Ventilatory efficiency (VE/VCO2 slope) change
    • Time Frame: 6 months
    • Difference in the interval changes from baseline and 6 months in the VE/VCO2 slope comparing sacubitril/valsartan with perindopril.
  • LVEF change
    • Time Frame: 6 months
    • Difference in the interval changes from baseline in LVEF, LVESV, and left LVEDV at 6 months, comparing sacubitril/valsartan with perindopril.
  • N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) change
    • Time Frame: Baseline, 3, 6 months
    • Change in concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline to 3 months , 6 months.
  • The MOS item short form health survey, SF-36
    • Time Frame: baseline and 6 months
    • A 36-item short-form (SF-36) was constructed to survey health status in the Medical Outcomes Study. The SF-36 was designed for use in clinical practice and research, health policy evaluations, and general population surveys. The SF-36 includes one multi-item scale that assesses eight health concepts. The higher scores mean a better outcome.

Participating in This Clinical Trial

Inclusion Criteria

1. Acute myocardial infarction (AMI) within 1 months prior to recruitment;

2. Aged 18 years or over and under 80 years;

3. Randomized patients will have been hemodynamically stable, SBP ≥100mmHg, no symptomatic hypotension;

4. NYHA Class Ⅱ-Ⅳ, HFrEF or HFpEF;

5. Elevated NT-proBNP or BNP at the time of screening;

6. Peak VO2/kg<16 ml/kg/min by CPET

Exclusion Criteria

1. Inability to complete a CPET;

2. Symptomatic hypotension and/or systolic blood pressure <100mmHg;

3. eGFR < 30 mL/min/1.73m2 and/or serum potassium >5.2mmol/L;

4. History of hypersensitivity or allergy to ACE-inhibitors/ARB

5. History of angioedema;

6. Pregnancy, planning pregnancy, or breast feeding;

7. Life-threatening diseases with limited life expectancy <1 year

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 80 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • RenJi Hospital
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Qin Shao, M.D,Ph.D, Study Chair, RenJi Hospital
    • Jun Ma, M.D,Ph.D, Study Director, RenJi Hospital
  • Overall Contact(s)
    • Qin Shao, M.D,Ph.D, 86-21-68385225, shaoqindr@126.com

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