1. Camm J, et al. On Behalf of The SHIFT Gothenburg, Cardiac safety of selective heart rate reduction with Ivabradine in chronic heart failure. Poster, Heart Failure Congress; 2011 May. Hot Topic from Gothenburg heart failure congress Insights from the SHIFT ECG-Holter Substudy Cardiac Safety of Selective Heart Rate Reduction with Ivabradine in Chronic Heart Failure

2. Rational & objective The results of the SHIFT study showed that the addition of ivabradine to guideline-based treatment significantly reduced the primary end point of cardiovascular death and hospitalization for heart failure with an excellent safety profile. 1 To complete the safety assessment, it was investigated whether specific heart rate lowering with ivabradine was associated with effects on the heart rhythm safety profile; this was explored over a 24-hour period in a prespecified ECG Holter ancillary study of the SHIFT study. 2 1- Swedberg K, Komajda M, Böhm M, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010;376:875-885. 2 - Camm. J, et al. On Behalf of The SHIFT Gothenburg, Cardiac safety of selective heart rate reduction with Ivabradine in chronic heart failure. Poster, Heart Failure Congress. 2011 May. ECG-Holter

3. Holter ECG analysis was performed at baseline and after 8 months Run-in 7 to 30 days D014 D028 ASSE HR and tolerability Ivabradine 5 mg, bid Matching placebo, bid Run-in 7 to 30 days D014 D028 ASSE Ivabradine 2.5, 5 or 7.5 mg bid according to M008 Holter ECG D000 Holter ECG M004 ECG-Holter

4. Heart rate reduction with ivabradine compared with placebo at baseline and at month Heart rate reduction with ivabradine tends to be greater during the waking hours than at night 24-hour heart rate control with ivabradine ECG-Holter Heart rate reduction with ivabradine at night and during the day, at month 8 compared with baseline Camm J et al. Eur of HF supplements 2011; 10(51), S134; abstract P797

5. Ivabradine offers good cardiac safety Table I. Results from ambulatory 24-hour electrocardiographic Holter monitoring after 8 months of treatment. ECG-Holter Camm J et al. Eur of HF supplements 2011; 10(51), S134; abstract P797

6. Conclusion The electrocardiographic safety profile of ivabradine in chronic heart failure patients treated with recommended therapy, including β-blockers is confirmed. Ivabradine provides effective heart rate reduction over 24 hours with good cardiac safety. Those results are reassuring with respect to use of ivabradine in clinical practice and complement the wide cardiac safety assessment of ivabradine.