Efficacy and safety of sacubitril/valsartan (LCZ696) in Japanese patients with chronic heart failure and reduced ejection fraction

Rationale for and design of the randomized, double-blind PARALLEL-HF study

Hiroyuki Tsutsui, Shinichi Momomura, Yoshihiko Saito, Hiroshi Itoh, Kazuhiro Yamamoto, Tomomi Ohishi, Naoko Okino, Weinong Guo

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background The prognosis of heart failure patients with reduced ejection fraction (HFrEF) in Japan remains poor, although there is growing evidence for increasing use of evidence-based pharmacotherapies in Japanese real-world HF registries. Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor shown to reduce mortality and morbidity in the recently completed largest outcome trial in patients with HFrEF (PARADIGM-HF trial). The prospectively designed phase III PARALLEL-HF (Prospective comparison of ARNI with ACE inhibitor to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients) study aims to assess the clinical efficacy and safety of LCZ696 in Japanese HFrEF patients, and show similar improvements in clinical outcomes as the PARADIGM-HF study enabling the registration of LCZ696 in Japan. Methods and design This is a multicenter, randomized, double-blind, parallel-group, active controlled study of 220 Japanese HFrEF patients. Eligibility criteria include a diagnosis of chronic HF (New York Heart Association Class II-IV) and reduced ejection fraction (left ventricular ejection fraction ≤35%) and increased plasma concentrations of natriuretic peptides [N-terminal pro B-type natriuretic peptide (NT-proBNP) ≥600 pg/mL, or NT-proBNP ≥400 pg/mL for those who had a hospitalization for HF within the last 12 months] at the screening visit. The study consists of three phases: (i) screening, (ii) single-blind active LCZ696 run-in, and (iii) double-blind randomized treatment. Patients tolerating LCZ696 50 mg bid during the treatment run-in are randomized (1:1) to receive LCZ696 100 mg bid or enalapril 5 mg bid for 4 weeks followed by up-titration to target doses of LCZ696 200 mg bid or enalapril 10 mg bid in a double-blind manner. The primary outcome is the composite of cardiovascular death or HF hospitalization and the study is an event-driven trial. Conclusions The design of the PARALLEL-HF study is aligned with the PARADIGM-HF study and aims to assess the efficacy and safety of LCZ696 in Japanese HFrEF patients.

Original languageEnglish
Pages (from-to)225-231
Number of pages7
JournalJournal of Cardiology
Volume70
Issue number3
DOIs
Publication statusPublished - Sep 1 2017

Fingerprint

Heart Failure
Safety
Enalapril
Brain Natriuretic Peptide
Japan
Hospitalization
LCZ 696
Neprilysin
Natriuretic Peptides
Angiotensin Receptors
Angiotensin-Converting Enzyme Inhibitors
Stroke Volume
Registries
Therapeutics
Morbidity
Drug Therapy
Mortality

Keywords

  • Heart failure with reduced ejection fraction
  • Japanese
  • LCZ696
  • Neprilysin
  • Sacubitril/valsartan

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Efficacy and safety of sacubitril/valsartan (LCZ696) in Japanese patients with chronic heart failure and reduced ejection fraction : Rationale for and design of the randomized, double-blind PARALLEL-HF study. / Tsutsui, Hiroyuki; Momomura, Shinichi; Saito, Yoshihiko; Itoh, Hiroshi; Yamamoto, Kazuhiro; Ohishi, Tomomi; Okino, Naoko; Guo, Weinong.

In: Journal of Cardiology, Vol. 70, No. 3, 01.09.2017, p. 225-231.

Research output: Contribution to journalArticle

Tsutsui, Hiroyuki ; Momomura, Shinichi ; Saito, Yoshihiko ; Itoh, Hiroshi ; Yamamoto, Kazuhiro ; Ohishi, Tomomi ; Okino, Naoko ; Guo, Weinong. / Efficacy and safety of sacubitril/valsartan (LCZ696) in Japanese patients with chronic heart failure and reduced ejection fraction : Rationale for and design of the randomized, double-blind PARALLEL-HF study. In: Journal of Cardiology. 2017 ; Vol. 70, No. 3. pp. 225-231.
@article{f522c3b6b6374d28bbcf91ef709d8ea7,
title = "Efficacy and safety of sacubitril/valsartan (LCZ696) in Japanese patients with chronic heart failure and reduced ejection fraction: Rationale for and design of the randomized, double-blind PARALLEL-HF study",
abstract = "Background The prognosis of heart failure patients with reduced ejection fraction (HFrEF) in Japan remains poor, although there is growing evidence for increasing use of evidence-based pharmacotherapies in Japanese real-world HF registries. Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor shown to reduce mortality and morbidity in the recently completed largest outcome trial in patients with HFrEF (PARADIGM-HF trial). The prospectively designed phase III PARALLEL-HF (Prospective comparison of ARNI with ACE inhibitor to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients) study aims to assess the clinical efficacy and safety of LCZ696 in Japanese HFrEF patients, and show similar improvements in clinical outcomes as the PARADIGM-HF study enabling the registration of LCZ696 in Japan. Methods and design This is a multicenter, randomized, double-blind, parallel-group, active controlled study of 220 Japanese HFrEF patients. Eligibility criteria include a diagnosis of chronic HF (New York Heart Association Class II-IV) and reduced ejection fraction (left ventricular ejection fraction ≤35{\%}) and increased plasma concentrations of natriuretic peptides [N-terminal pro B-type natriuretic peptide (NT-proBNP) ≥600 pg/mL, or NT-proBNP ≥400 pg/mL for those who had a hospitalization for HF within the last 12 months] at the screening visit. The study consists of three phases: (i) screening, (ii) single-blind active LCZ696 run-in, and (iii) double-blind randomized treatment. Patients tolerating LCZ696 50 mg bid during the treatment run-in are randomized (1:1) to receive LCZ696 100 mg bid or enalapril 5 mg bid for 4 weeks followed by up-titration to target doses of LCZ696 200 mg bid or enalapril 10 mg bid in a double-blind manner. The primary outcome is the composite of cardiovascular death or HF hospitalization and the study is an event-driven trial. Conclusions The design of the PARALLEL-HF study is aligned with the PARADIGM-HF study and aims to assess the efficacy and safety of LCZ696 in Japanese HFrEF patients.",
keywords = "Heart failure with reduced ejection fraction, Japanese, LCZ696, Neprilysin, Sacubitril/valsartan",
author = "Hiroyuki Tsutsui and Shinichi Momomura and Yoshihiko Saito and Hiroshi Itoh and Kazuhiro Yamamoto and Tomomi Ohishi and Naoko Okino and Weinong Guo",
year = "2017",
month = "9",
day = "1",
doi = "10.1016/j.jjcc.2016.11.011",
language = "English",
volume = "70",
pages = "225--231",
journal = "Journal of cardiography. Supplement",
issn = "0914-5087",
publisher = "Japanese College of Cardiology (Nippon-Sinzobyo-Gakkai)",
number = "3",

}

TY - JOUR

T1 - Efficacy and safety of sacubitril/valsartan (LCZ696) in Japanese patients with chronic heart failure and reduced ejection fraction

T2 - Rationale for and design of the randomized, double-blind PARALLEL-HF study

AU - Tsutsui, Hiroyuki

AU - Momomura, Shinichi

AU - Saito, Yoshihiko

AU - Itoh, Hiroshi

AU - Yamamoto, Kazuhiro

AU - Ohishi, Tomomi

AU - Okino, Naoko

AU - Guo, Weinong

PY - 2017/9/1

Y1 - 2017/9/1

N2 - Background The prognosis of heart failure patients with reduced ejection fraction (HFrEF) in Japan remains poor, although there is growing evidence for increasing use of evidence-based pharmacotherapies in Japanese real-world HF registries. Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor shown to reduce mortality and morbidity in the recently completed largest outcome trial in patients with HFrEF (PARADIGM-HF trial). The prospectively designed phase III PARALLEL-HF (Prospective comparison of ARNI with ACE inhibitor to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients) study aims to assess the clinical efficacy and safety of LCZ696 in Japanese HFrEF patients, and show similar improvements in clinical outcomes as the PARADIGM-HF study enabling the registration of LCZ696 in Japan. Methods and design This is a multicenter, randomized, double-blind, parallel-group, active controlled study of 220 Japanese HFrEF patients. Eligibility criteria include a diagnosis of chronic HF (New York Heart Association Class II-IV) and reduced ejection fraction (left ventricular ejection fraction ≤35%) and increased plasma concentrations of natriuretic peptides [N-terminal pro B-type natriuretic peptide (NT-proBNP) ≥600 pg/mL, or NT-proBNP ≥400 pg/mL for those who had a hospitalization for HF within the last 12 months] at the screening visit. The study consists of three phases: (i) screening, (ii) single-blind active LCZ696 run-in, and (iii) double-blind randomized treatment. Patients tolerating LCZ696 50 mg bid during the treatment run-in are randomized (1:1) to receive LCZ696 100 mg bid or enalapril 5 mg bid for 4 weeks followed by up-titration to target doses of LCZ696 200 mg bid or enalapril 10 mg bid in a double-blind manner. The primary outcome is the composite of cardiovascular death or HF hospitalization and the study is an event-driven trial. Conclusions The design of the PARALLEL-HF study is aligned with the PARADIGM-HF study and aims to assess the efficacy and safety of LCZ696 in Japanese HFrEF patients.

AB - Background The prognosis of heart failure patients with reduced ejection fraction (HFrEF) in Japan remains poor, although there is growing evidence for increasing use of evidence-based pharmacotherapies in Japanese real-world HF registries. Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor shown to reduce mortality and morbidity in the recently completed largest outcome trial in patients with HFrEF (PARADIGM-HF trial). The prospectively designed phase III PARALLEL-HF (Prospective comparison of ARNI with ACE inhibitor to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients) study aims to assess the clinical efficacy and safety of LCZ696 in Japanese HFrEF patients, and show similar improvements in clinical outcomes as the PARADIGM-HF study enabling the registration of LCZ696 in Japan. Methods and design This is a multicenter, randomized, double-blind, parallel-group, active controlled study of 220 Japanese HFrEF patients. Eligibility criteria include a diagnosis of chronic HF (New York Heart Association Class II-IV) and reduced ejection fraction (left ventricular ejection fraction ≤35%) and increased plasma concentrations of natriuretic peptides [N-terminal pro B-type natriuretic peptide (NT-proBNP) ≥600 pg/mL, or NT-proBNP ≥400 pg/mL for those who had a hospitalization for HF within the last 12 months] at the screening visit. The study consists of three phases: (i) screening, (ii) single-blind active LCZ696 run-in, and (iii) double-blind randomized treatment. Patients tolerating LCZ696 50 mg bid during the treatment run-in are randomized (1:1) to receive LCZ696 100 mg bid or enalapril 5 mg bid for 4 weeks followed by up-titration to target doses of LCZ696 200 mg bid or enalapril 10 mg bid in a double-blind manner. The primary outcome is the composite of cardiovascular death or HF hospitalization and the study is an event-driven trial. Conclusions The design of the PARALLEL-HF study is aligned with the PARADIGM-HF study and aims to assess the efficacy and safety of LCZ696 in Japanese HFrEF patients.

KW - Heart failure with reduced ejection fraction

KW - Japanese

KW - LCZ696

KW - Neprilysin

KW - Sacubitril/valsartan

UR - http://www.scopus.com/inward/record.url?scp=85008193284&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85008193284&partnerID=8YFLogxK

U2 - 10.1016/j.jjcc.2016.11.011

DO - 10.1016/j.jjcc.2016.11.011

M3 - Article

VL - 70

SP - 225

EP - 231

JO - Journal of cardiography. Supplement

JF - Journal of cardiography. Supplement

SN - 0914-5087

IS - 3

ER -