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 Komajda M et al. Eur J Heart Fail. 2014;16(7):

<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= for difference between the groups Outcomes in placebo patients grouped according to tertiles of systolic blood pressure and resting heart rate Komajda M et al. Eur J Heart Fail. 2014;16(7):

Time (years) <115 mm Hg to <130 mm Hg ≥130 mm Hg Numbers at risk P= 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), % Komajda M et al. Eur J Heart Fail. 2014;16(7):

Baseline systolic blood pressure <115 mm Hg Placebo Ivabradine 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 Komajda M et al. Eur J Heart Fail. 2014;16(7):

Placebo Ivabradine 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 Komajda M et al. Eur J Heart Fail. 2014;16(7):

Placebo Ivabradine 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 Komajda M et al. Eur J Heart Fail. 2014;16(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 Komajda M et al. Eur J Heart Fail. 2014;16(7): P for interaction =0.68

Adjusted hazard ratio P-value P-value for interaction Cardiovascular mortality <115 mm Hg to <130 mm Hg ≥130 mm Hg Hospitalization for worsening heart failure <115 mm Hg to <130 mm Hg ≥130 mm Hg Heart failure mortality <115 mm Hg to <130 mm Hg ≥130 mm Hg All-cause mortality <115 mm Hg to <130 mm Hg ≥130 mm Hg Effect of ivabradine on other outcomes according to baseline systolic blood pressure Komajda M et al. Eur J Heart Fail. 2014;16(7):

SBP, mm Hg< to <130≥130 IVA, %PL, %PIVA, %PL, %PIVA, %PL, %P Symptomatic bradycardia Asymptomatic bradycardia Atrial fibrillation Phosphenes Hypotension according to systolic blood pressure level Adverse event leading to withdrawal according to systolic blood pressure level Komajda M et al. Eur J Heart Fail. 2014;16(7):