Effect of ivabradine-induced heart rate reduction on flow-mediated dilation measured with high-sensitivity ultrasound in patients with stable coronary heart disease.
BACKGROUND
Experimental data suggests that exclusive heart rate reduction with ivabradine is associated with the amelioration of the endothelial function. Since it is presently unknown whether this also applies to humans, the aim of this pilot study was to investigate whether heart rate reduction with ivabradine modulates the endothelial function in humans with an established coronary heart disease.


METHODS
Using high-sensitivity ultrasound, we analysed the flow-mediated (FMD) and nitro-mediated dilation (NMD) of the brachial artery in 25 patients (62.9 ± 8.4 years) with a stable coronary heart disease and a resting heart rate of ≥70 beats per minute (bpm). To assess acute effects, measurements were performed before and 4 hours after the first intake of ivabradine 7.5 mg. Sustained effects of an ivabradine therapy (5 mg to 7.5 mg twice daily) were investigated after 4 weeks.


RESULTS
We found a significant decrease in heart rate, both 4 hours after the intake of 7.5 mg of ivabradine (median -8 [interquartile range (IQR) -14 to -4] bpm) and after 4 weeks of twice daily intake (median -10 [IQR-17 to -5] bpm) (p < 0.05). However, the FMD did not change significantly: neither after first dose of ivabradine nor after sustained therapy (baseline FMD: median 5.0 [IQR 2.4 to 7.9]%; FMD 4 hours after 7.5 mg of ivabradine: median 4.9 [IQR 2.7 to 9.8]%; FMD after 4 weeks of ivabradine therapy: median 6.1 [IQR 4.3 to 8.2]%). No significant changes of the NMD were observed. In regression analysis, the heart rate and FMD did not correlated, irrespective of the ivabradine intake (r2 = 0.086).


CONCLUSIONS
In conclusion, in our study heart rate reduction through ivabradine does not improve the endothelial function in patients with a stable coronary heart disease. Moreover, we found no correlation between the heart rate and the endothelial function.
Asklepios Klinik St, Georg, Klinische und interventionelle Angiologie, Lohmühlenstraße 5, 20099 Hamburg, Germany. n.jochmann@asklepios.com.
Nicoline
N
Jochmann
Franziska
F
Schröter
Fabian
F
Knebel
Robert
R
Hättasch
Christine
C
Gericke
Karl
K
Stangl
Gert
G
Baumann
Verena
V
Stangl
D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D001552:Benzazepines / Q000627:therapeutic use*; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology*; D003326:Coronary Circulation / Q000187:drug effects*; D004452:Echocardiography / Q000379:methods; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D000077550:Ivabradine; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D000889:Anti-Arrhythmia Agents; D001552:Benzazepines; D000077550:Ivabradine