TY - JOUR
T1 - Rationale, design, and baseline characteristics of the Study assessInG the morbidity-mortality beNefits of the If inhibitor ivabradine in patients with coronarY artery disease (SIGNIFY trial)
T2 - a randomized, double-blind, placebo-controlled trial of ivabradine in patients with stable coronary artery disease without clinical heart failure
AU - Fox, Kim
AU - Ford, Ian
AU - Steg, Philippe Gabriel
AU - Tardif, Jean-Claude
AU - Tendera, Michal
AU - Ferrari, Roberto
AU - Murray, Gordon
N1 - © 2013.
PY - 2013/10
Y1 - 2013/10
N2 - BACKGROUND: Elevated heart rate in stable coronary artery disease (CAD) is associated with worse outcomes, particularly increased risk of myocardial infarction. Heart rate reduction with the If inhibitor ivabradine confers symptomatic benefits in angina pectoris and reduces coronary events in patients with stable CAD and left ventricular (LV) systolic dysfunction, with a resting heart rate of ≥70 beats/min. The SIGNIFY trial is testing the hypothesis that heart rate reduction using ivabradine reduces mortality and cardiovascular events in patients with stable CAD, but without clinical heart failure.METHODS: The SIGNIFY trial is a randomized, double-blind, parallel-group, placebo-controlled, event-driven study in patients with stable CAD (1,139 centers, 51 countries). Participants are 55 years or older, with stable CAD and an LV ejection fraction >40%, in sinus rhythm, with a baseline resting heart rate of ≥70 beats/min, and with at least 1 additional cardiovascular risk factor. At inclusion, patients receive ivabradine 7.5 mg twice a day or matching placebo, which is adjusted at every visit to a heart rate target of 60 beats/min. Participants should receive the best possible background treatment for stable CAD. The primary end point is a composite of cardiovascular death or nonfatal myocardial infarction.RESULTS: Recruitment lasted from October 2009 to April 2012. The SIGNIFY trial has recruited 19,102 patients (age 65.0 ± 7.2 years, resting heart rate 77.2 ± 7.0 beats/min, 72% male) with no evidence for LV dysfunction (ejection fraction 56.5% ± 8.6%).CONCLUSION: The SIGNIFY trial will shed further light on the role of heart rate lowering with ivabradine in patients with stable CAD without clinical heart failure. The study is expected to end in 2014.
AB - BACKGROUND: Elevated heart rate in stable coronary artery disease (CAD) is associated with worse outcomes, particularly increased risk of myocardial infarction. Heart rate reduction with the If inhibitor ivabradine confers symptomatic benefits in angina pectoris and reduces coronary events in patients with stable CAD and left ventricular (LV) systolic dysfunction, with a resting heart rate of ≥70 beats/min. The SIGNIFY trial is testing the hypothesis that heart rate reduction using ivabradine reduces mortality and cardiovascular events in patients with stable CAD, but without clinical heart failure.METHODS: The SIGNIFY trial is a randomized, double-blind, parallel-group, placebo-controlled, event-driven study in patients with stable CAD (1,139 centers, 51 countries). Participants are 55 years or older, with stable CAD and an LV ejection fraction >40%, in sinus rhythm, with a baseline resting heart rate of ≥70 beats/min, and with at least 1 additional cardiovascular risk factor. At inclusion, patients receive ivabradine 7.5 mg twice a day or matching placebo, which is adjusted at every visit to a heart rate target of 60 beats/min. Participants should receive the best possible background treatment for stable CAD. The primary end point is a composite of cardiovascular death or nonfatal myocardial infarction.RESULTS: Recruitment lasted from October 2009 to April 2012. The SIGNIFY trial has recruited 19,102 patients (age 65.0 ± 7.2 years, resting heart rate 77.2 ± 7.0 beats/min, 72% male) with no evidence for LV dysfunction (ejection fraction 56.5% ± 8.6%).CONCLUSION: The SIGNIFY trial will shed further light on the role of heart rate lowering with ivabradine in patients with stable CAD without clinical heart failure. The study is expected to end in 2014.
KW - Aged
KW - Benzazepines
KW - Coronary Artery Disease
KW - Cyclic Nucleotide-Gated Cation Channels
KW - Dose-Response Relationship, Drug
KW - Double-Blind Method
KW - Female
KW - Follow-Up Studies
KW - Heart Failure
KW - Heart Rate
KW - Humans
KW - Male
KW - Middle Aged
KW - Morbidity
KW - Retrospective Studies
KW - Stroke Volume
KW - Survival Rate
KW - Treatment Outcome
KW - Ventricular Function, Left
KW - World Health
U2 - 10.1016/j.ahj.2013.06.024
DO - 10.1016/j.ahj.2013.06.024
M3 - Article
C2 - 24093844
VL - 166
SP - 654-661.e6
JO - American Heart Journal
JF - American Heart Journal
SN - 0002-8703
IS - 4
ER -