19 102 patients, 51 countries, 1139 centersFox K, Ford I, Steg PG, Tardif JC, Tendera M, Ferrari R. 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): A randomized, double-blind, placebo-controlled trial of ivabradine in patients with stable coronary artery disease without clinical heart failure. Am Heart J. 2013;166:654-661.

The SIGNIFY studyThe SIGNIFY study

Study designStudy design

Mean follow-up of 2.75 years

Fox K, Ford I, Steg PG, Tardif JC, Tendera M, Ferrari R. 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): A randomized, double-blind, placebo-controlled trial of ivabradine in patients with stable coronary artery disease without clinical heart failure. Am Heart J. 2013;166:654-661.

Study populationStudy population

• Proven stable CADProven stable CAD• Age >55 years Age >55 years • Without LVSD (EF >40%, no clinical signs of HF)Without LVSD (EF >40%, no clinical signs of HF)• In sinus rhythm, with a resting heart rate >70 bpmIn sinus rhythm, with a resting heart rate >70 bpm• Receiving appropriate stable conventional Receiving appropriate stable conventional

cardiovascular medicationcardiovascular medication• With one or more other cardiovascular risk factorsWith one or more other cardiovascular risk factors

Fox K, Ford I, Steg PG, Tardif JC, Tendera M, Ferrari R. 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): A randomized, double-blind, placebo-controlled trial of ivabradine in patients with stable coronary artery disease without clinical heart failure. Am Heart J. 2013;166:654-661.

Study end pointsStudy end points

Cardiovascular death or nonfatal myocardial infarctionPrimary composite end pointPrimary composite end point

Secondary end pointsSecondary end pointsAll-cause deathCardiovascular deathCoronary deathNonfatal myocardial infarctionCoronary revascularizationElective coronary revascularizationNew-onset or worsening heart failure

Fox K, Ford I, Steg PG, Tardif JC, Tendera M, Ferrari R. 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): A randomized, double-blind, placebo-controlled trial of ivabradine in patients with stable coronary artery disease without clinical heart failure. Am Heart J. 2013;166:654-661.

Fox K, Ford I, Steg PG, Tardif JC, Tendera M, Ferrari R. 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): A randomized, double-blind, placebo-controlled trial of ivabradine in patients with stable coronary artery disease without clinical heart failure. Am Heart J. 2013;166:654-661.

Baseline characteristicsBaseline characteristics

Whole population (N = 19 102)Demographic characteristicsAge (y)<70≥70≥75Body mass index (kg/m2)Heart rate (beats/min)MaleEthnic originWhiteAsianOtherSystolic blood pressure (mm Hg)Diastolic blood pressure (mm Hg)CAD duration (y)

65.0 ± 7.213 669 (72)5433 (28)2227 (12)28.8 ± 4.677.2 ± 7.013 840 (72) 15 532 (81)2547 (13)1022 (5)130.5 ± 13.678.2 ± 8.26.2 ± 6.3

Values are means SD or n (%).

Fox K, Ford I, Steg PG, Tardif JC, Tendera M, Ferrari R. 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): A randomized, double-blind, placebo-controlled trial of ivabradine in patients with stable coronary artery disease without clinical heart failure. Am Heart J. 2013;166:654-661.

Baseline characteristicsBaseline characteristics

Fox K, Ford I, Steg PG, Tardif JC, Tendera M, Ferrari R. 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): A randomized, double-blind, placebo-controlled trial of ivabradine in patients with stable coronary artery disease without clinical heart failure. Am Heart J. 2013;166:654-661.

Baseline characteristicsBaseline characteristics

Planned substudiesPlanned substudies

Fox K, Ford I, Steg PG, Tardif JC, Tendera M, Ferrari R. 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): A randomized, double-blind, placebo-controlled trial of ivabradine in patients with stable coronary artery disease without clinical heart failure. Am Heart J. 2013;166:654-661.

• The Quality of Life Substudy is designed to evaluate changes in the Seattle Angina Questionnaire in 4500 patients with angina pectoris at baseline (CCS class II or higher), depending on the availability of an approved translation of the questionnaire.

• The aim of the Biomarkers Substudy is to detect changes in circulating von Willebrand factor, as well as high-sensitivity troponin T and other biomarkers of CAD progression and endothelial function, in a group of 380 patients at baseline and at 3 and 12 months, in centers that meet the technical requirements.

• The Pharmacogenomics Substudy will analyze whether genetic variations in candidate genes and in the whole genome are associated with clinical outcomes in about 5000 patients in countries where such studies receive ethical/regulatory approval.

Official study websiteOfficial study website

Read more about SIGNIFY atRead more about SIGNIFY atwww.signify-study.com