Abstract
Increased heart rate (HR) is an independent risk factor for cardiovascular outcomes in chronic heart failure (HF). Ivabradine, anIfinhibitor, improved outcomes in patients with HF and reduced ejection fraction (HFrEF) in the SHIFT study. We evaluated its efficacy and safety in Japanese HFrEF patients in a randomized, double-blind, placebo-controlled phase III study: the J-SHIFT study. The main objective was to confirm a hazard ratio of <1 in the primary composite endpoint of cardiovascular death or hospital admission for worsening HF.Methods and Results:Patients with NYHA functional class II-IV, left ventricular EF ≤35%, and resting HR ≥75 beats/min in sinus rhythm under optimal medical therapy received ivabradine (n=127) or placebo (n=127). Mean reduction in resting HR was significantly greater in the ivabradine group (15.2 vs. 6.1 beats/min, P<0.0001). However, symptomatic bradycardia did not occur. A total of 26 (20.5%) patients in the ivabradine group and 37 (29.1%) patients in the placebo group had the primary endpoint event (hazard ratio 0.67, 95% CI 0.40-1.11, P=0.1179) during median follow-up of 589 days. Mild phosphenes were reported in 8 (6.3%) patients in the ivabradine group and 4 (3.1%) patients in the placebo grou...Continue Reading
References
Oct 13, 2005·European Heart Journal·Stuart J PocockChristopher B Granger
Jan 11, 2007·British Journal of Pharmacology·L CervettoC Gargini
Jun 15, 2007·Annals of Medicine·Richard W TroughtonM Gary Nicholls
Mar 1, 2008·Cardiovascular Drugs and Therapy·Jens RosenbergPer Rossen Hildebrandt
Aug 31, 2010·Lancet·Karl SwedbergUNKNOWN SHIFT Investigators
Nov 30, 2010·International Journal of Cardiology·C CeconiUNKNOWN BEAUTIFUL Echo-BNP Investigators
Aug 31, 2011·European Heart Journal·Jean-Claude TardifUNKNOWN SHIFT Investigators
May 12, 2012·Clinical Research in Cardiology : Official Journal of the German Cardiac Society·Michael BöhmLuigi Tavazzi
Dec 4, 2012·The EPMA Journal·Nobuyuki Shiba, Hiroaki Shimokawa
Feb 23, 2013·International Heart Journal·Yoshihiro MoriKatsutoshi Hiramatsu
Apr 6, 2013·Heart and Vessels·Masatsugu HoriMasunori Matsuzaki
Jan 15, 2016·Circulation Journal : Official Journal of the Japanese Circulation Society·Hiroyuki TsutsuiUNKNOWN study investigators
Aug 22, 2017·Circulation Journal : Official Journal of the Japanese Circulation Society·Hiroyuki TsutsuiUNKNOWN J-EMPHASIS-HF Study Group
Jan 5, 2019·Circulation Journal : Official Journal of the Japanese Circulation Society·Tomomi IdeHiroyuki Tsutsui
Citations
Aug 30, 2019·Circulation Journal : Official Journal of the Japanese Circulation Society·Yoshihiro Seo, Nobuyuki Ohte
May 29, 2020·Internal Medicine·Teruhiko Imamura
Jun 28, 2020·ESC Heart Failure·Toshihide IzumidaKoichiro Kinugawa
Feb 18, 2020·Circulation Journal : Official Journal of the Japanese Circulation Society·Toyoaki Murohara
Apr 1, 2020·International Heart Journal·Hisataka Maki, Norihiko Takeda
Aug 4, 2020·Circulation Journal : Official Journal of the Japanese Circulation Society·Sho OkadaYoshio Kobayashi
Aug 10, 2020·Current Cardiology Reports·Domenico D'AmarioGianluigi Savarese
Aug 4, 2020·Circulation Journal : Official Journal of the Japanese Circulation Society·Hiroyuki TsutsuiYasushi Kawasaki
Oct 3, 2020·Cardiology and Therapy·Ajit Mullasari, UNKNOWN PROFICIENT investigators
Oct 23, 2020·Internal Medicine·Masakazu HoriKoichiro Kinugawa
Nov 5, 2020·The Cochrane Database of Systematic Reviews·Carina BenstoemVincent Brandenburg
Nov 9, 2020·Clinical Therapeutics·Hongbing WanQinghua Wu
Jan 28, 2021·Clinical Drug Investigation·Shunsuke KiuchiTakanori Ikeda
Feb 5, 2021·Journal of Cardiac Surgery·Teruhiko ImamuraKoichiro Kinugawa
Feb 28, 2021·Clinical Cardiology·Sasmita Bryan RichardSuxin Luo
Mar 12, 2021·Circulation Reports·Yuji NagatomoUNKNOWN J-CHF Investigators
Mar 30, 2021·Internal Medicine·Keisuke Kida
Jan 5, 2021·Journal of cardiology·Hidekazu TanakaKen-Ichi Hirata
Apr 13, 2021·Journal of Cardiology Cases·Takahiro OkumuraToyoaki Murohara
Apr 13, 2021·Journal of Cardiology Cases·Masakazu HoriKoichiro Kinugawa
Apr 24, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Toru KawadaMasaru Sugimachi
Oct 1, 2021·Circulation Journal : Official Journal of the Japanese Circulation Society·Hiroyuki TsutsuiUNKNOWN Japanese Circulation Society and the Japanese Heart Failure Society Joint Working Group
Dec 11, 2021·Physiological Reports·Toru KawadaKeita Saku