2. 19 102 patients, 51 countries, 1139 centers 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 I f 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 study

3. Study 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 I f 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.

4. Study population Proven stable CAD Proven 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 bpm In sinus rhythm, with a resting heart rate >70 bpm Receiving appropriate stable conventional cardiovascular medication Receiving appropriate stable conventional cardiovascular medication With one or more other cardiovascular risk factors With 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 I f 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.

5. Study end points Cardiovascular death or nonfatal myocardial infarction Primary composite end point Secondary end points All-cause death Cardiovascular death Coronary death Nonfatal myocardial infarction Coronary revascularization Elective coronary revascularization New-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 I f 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.

6. Baseline characteristics Whole population (N = 19 102) Demographic characteristics Age (y) <70 70 75 Body mass index (kg/m 2 ) Heart rate (beats/min) Male Ethnic origin White Asian Other Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) CAD duration (y) 65.0 ± 7.2 13 669 (72) 5433 (28) 2227 (12) 28.8 ± 4.6 77.2 ± 7.0 13 840 (72) 15 532 (81) 2547 (13) 1022 (5) 130.5 ± 13.6 78.2 ± 8.2 6.2 ± 6.3 Values are means SD or n (%).

7. 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 I f 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 characteristics

8. 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 I f 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 characteristics

9. Planned 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 I f 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.

10. Official study website Read more about SIGNIFY at www.signify-study.com