Ivabradine in stable coronary artery disease without clinical heart failure

Fox, Kim, Ford, Ian, Steg, Philippe Gabriel, Tardif, Jean-Claude, Tendera, Michal, Ferrari, Roberto, SIGNIFY Investigators and Colquhoun, David (2014) Ivabradine in stable coronary artery disease without clinical heart failure. New England Journal of Medicine, 371 12: 1091-1099. doi:10.1056/NEJMoa1406430

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Author Fox, Kim
Ford, Ian
Steg, Philippe Gabriel
Tardif, Jean-Claude
Tendera, Michal
Ferrari, Roberto
SIGNIFY Investigators
Colquhoun, David
Title Ivabradine in stable coronary artery disease without clinical heart failure
Journal name New England Journal of Medicine   Check publisher's open access policy
ISSN 1533-4406
Publication date 2014-09-18
Year available 2014
Sub-type Article (original research)
DOI 10.1056/NEJMoa1406430
Open Access Status File (Publisher version)
Volume 371
Issue 12
Start page 1091
End page 1099
Total pages 9
Place of publication Waltham, United States
Publisher Massachussetts Medical Society
Language eng
Formatted abstract
An elevated heart rate is an established marker of cardiovascular risk. Previous analyses have suggested that ivabradine, a heart-rate–reducing agent, may improve outcomes in patients with stable coronary artery disease, left ventricular dysfunction, and a heart rate of 70 beats per minute or more.

We conducted a randomized, double-blind, placebo-controlled trial of ivabradine, added to standard background therapy, in 19,102 patients who had both stable coronary artery disease without clinical heart failure and a heart rate of 70 beats per minute or more (including 12,049 patients with activity-limiting angina [class ≥II on the Canadian Cardiovascular Society scale, which ranges from I to IV, with higher classes indicating greater limitations on physical activity owing to angina]). We randomly assigned patients to placebo or ivabradine, at a dose of up to 10 mg twice daily, with the dose adjusted to achieve a target heart rate of 55 to 60 beats per minute. The primary end point was a composite of death from cardiovascular causes or nonfatal myocardial infarction.

At 3 months, the mean (±SD) heart rate of the patients was 60.7±9.0 beats per minute in the ivabradine group versus 70.6±10.1 beats per minute in the placebo group. After a median follow-up of 27.8 months, there was no significant difference between the ivabradine group and the placebo group in the incidence of the primary end point (6.8% and 6.4%, respectively; hazard ratio, 1.08; 95% confidence interval, 0.96 to 1.20; P=0.20), nor were there significant differences in the incidences of death from cardiovascular causes and nonfatal myocardial infarction. Ivabradine was associated with an increase in the incidence of the primary end point among patients with activity-limiting angina but not among those without activity-limiting angina (P=0.02 for interaction). The incidence of bradycardia was higher with ivabradine than with placebo (18.0% vs. 2.3%, P<0.001). 

Among patients who had stable coronary artery disease without clinical heart failure, the addition of ivabradine to standard background therapy to reduce the heart rate did not improve outcomes. (Funded by Servier; SIGNIFY Current Controlled Trials number, ISRCTN61576291.) 
Keyword Medicine, General & Internal
General & Internal Medicine
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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