The effect of heart rate reduction with ivabradine on renal function in patients with chronic heart failure: an analysis

from SHIFT

Systolic Heart failure treatment with

the If inhibitor ivabradine Trial

www.shift-study.comVoors AA et al. Eur J Heart Fail. 2014 Feb 7. [Epub ahead of print]

Effect of ivabradine on composite of CV death or HF hospitalization

00 6 12 18 24 30

10

20

30

40

50

Pat

ien

ts (

%)

Time (months)

Ivabradine, renal dysfunction

Placebo, renal dysfunction

N at risk

RD (pl) 799 706 612 488 261 95

RD (iva) 780 720 612 489 273 104

NRD (pl) 2293 2119 1847 1551 820 343

NRD (iva) 2288 2166 1963 1662 906 339

Placebo, no renal dysfunction

Ivabradine, no renal dysfunction

] P=0.023

] P <0.001

Voors AA et al. Eur J Heart Fail. 2014 Feb 7. [Epub ahead of print]

Event rate, n (%)Ivabradine Placebo HR P P interaction

Hospitalization for worsening heart failure

eGFR<60 mL/min/1.73 m² 22 27 0.78 0.0170.89

eGFR60 mL/min/1.73 m² 14 18 0.72 <0.001

Heart failure death

eGFR<60 mL/min/1.73 m² 5 6 0.88 0.560.37

eGFR60 mL/min/1.73 m² 2 3 0.68 0.040

Cardiovascular death

eGFR<60 mL/min/1.73 m² 15 16 0.95 0.690.68

eGFR60 mL/min/1.73 m² 10 11 0.89 0.20

Effect of ivabradine on other outcomes

Voors AA et al. Eur J Heart Fail. 2014 Feb 7. [Epub ahead of print]

Months

Placebo

Ivabradine

Cre

atin

ine,

μm

ol/L

140

130

120

110

100

90

80

70

600 5 10 15 20 25 30

Creatinine values over time with ivabradine and placebo

Voors AA et al. Eur J Heart Fail. 2014 Feb 7. [Epub ahead of print]

Conclusions

In a large trial in patients with chronic systolic HF, renal function generally remained stable

However, if renal function worsened, it was strongly associated with an increased risk for events

Baseline heart rate was directly & independently associated with risk of worsening renal function

Treatment with ivabradine had a neutral effect on renal function during 2 years of follow-up

The beneficial prognostic effects and safety of ivabradine were similar in patients with and without renal dysfunction

Voors AA et al. Eur J Heart Fail. 2014 Feb 7. [Epub ahead of print]