1. S ystolic H eart failure treatment with the I f inhibitor ivabradine T rial Efficacy and safety of ivabradine in patients with chronic systolic heart failure according to blood pressure level in SHIFT www.shift-study.com Komajda M et al. Eur J Heart Fail. 2014;16(7):810-816.

2. <74 bpm 74 to <81 bpm ≥81 bpm <115 mm Hg115 to <130 mm Hg≥130 mm Hg Rate of primary end point (cardiovascular mortality or hospitalization for worsening heart failure), % Systolic blood pressure at baseline Heart rate at baseline P=0.0058 for difference between the groups Outcomes in placebo patients grouped according to tertiles of systolic blood pressure and resting heart rate www.shift-study.com Komajda M et al. Eur J Heart Fail. 2014;16(7):810-816.

3. Time (years) <115 mm Hg 10699077595922881176 115 to <130 mm Hg 9918737606463501414 ≥130 mm Hg 120410889708234511817 Numbers at risk P=0.0003 for difference between the groups <115 mm Hg 115 to <130 mm Hg ≥130 mm Hg Outcomes in placebo patients according to tertiles of baseline systolic blood pressure Rate of primary end point (cardiovascular mortality or hospitalization for worsening heart failure), % www.shift-study.com Komajda M et al. Eur J Heart Fail. 2014;16(7):810-816.

4. Baseline systolic blood pressure <115 mm Hg Placebo 10699077595922881176 Ivabradine 10419117846242871153 Numbers at risk Incidence of primary end point (%) Placebo Ivabradine HR 0.84 (95% CI, 0.72 to 0.98), P=0.022 Time (years) Effect of ivabradine on primary outcomes (CV death or HF hospitalization) according to systolic blood pressure level www.shift-study.com Komajda M et al. Eur J Heart Fail. 2014;16(7):810-816.

5. Placebo 9918737606463501414 Ivabradine 9778747826643811314 Numbers at risk Incidence of primary end point (%) HR 0.86 (95% CI, 0.72 to 1.03), P=0.099 Time (years) Baseline systolic blood pressure 115 to <130 mm Hg Effect of ivabradine on primary outcomes (CV death or HF hospitalization) according to systolic blood pressure level Placebo Ivabradine www.shift-study.com Komajda M et al. Eur J Heart Fail. 2014;16(7):810-816.

6. Placebo 120410889708234511817 Ivabradine 1223114310348855232019 Numbers at risk Time (years) Incidence of primary end point (%) HR 0.77 (95% CI, 0.66 to 0.92), P=0.003 Baseline systolic blood pressure ≥130 mm Hg Effect of ivabradine on primary outcomes (CV death or HF hospitalization) according to systolic blood pressure level Placebo Ivabradine www.shift-study.com Komajda M et al. Eur J Heart Fail. 2014;16(7):810-816.

7. Baseline SBP <115 mm Hg HR 0.84 (95% CI, 0.72 to 0.98), P=0.022 Time (years) HR 0.86 (95% CI, 0.72 to 1.03), P=0.099 Time (years) Baseline SBP 115 to <130 mm Hg Time (years) HR 0.77 (95% CI, 0.66 to 0.92), P=0.003 Baseline SBP≥130 mm Hg Effect of ivabradine on primary outcomes (CV death or HF hospitalization) according to systolic blood pressure level Rate of primary end point (cardiovascular mortality or hospitalization for worsening heart failure), % Placebo Ivabradine Placebo Ivabradine Placebo Ivabradine www.shift-study.com Komajda M et al. Eur J Heart Fail. 2014;16(7):810-816. P for interaction =0.68

8. Adjusted hazard ratio P-value P-value for interaction Cardiovascular mortality <115 mm Hg0.890.24 0.91 115 to <130 mm Hg0.960.723 ≥130 mm Hg0.910.42 Hospitalization for worsening heart failure <115 mm Hg0.780.007 0.79 115 to <130 mm Hg0.740.005 ≥130 mm Hg0.710.001 Heart failure mortality <115 mm Hg0.710.046 0.18 115 to <130 mm Hg0.580.033 ≥130 mm Hg1.160.59 All-cause mortality <115 mm Hg0.920.36 0.90 115 to <130 mm Hg0.940.57 ≥130 mm Hg0.870.23 Effect of ivabradine on other outcomes according to baseline systolic blood pressure www.shift-study.com Komajda M et al. Eur J Heart Fail. 2014;16(7):810-816.

9. SBP, mm Hg<115115 to <130≥130 IVA, %PL, %PIVA, %PL, %PIVA, %PL, %P Symptomatic bradycardia 0.30.10.370.90.10.0110.70.20.14 Asymptomatic bradycardia 0.90.20.03110.20.0070.60.10.070 Atrial fibrillation 44.20.43430.25530.030 Phosphenes0.500.02900 0.2 0.69 Hypotension0.10.21.000.100.5000 according to systolic blood pressure level Adverse event leading to withdrawal according to systolic blood pressure level www.shift-study.com Komajda M et al. Eur J Heart Fail. 2014;16(7):810-816.