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01.06.2014 | Original Paper | Ausgabe 6/2014

Clinical Research in Cardiology 6/2014

Ivabradine therapy to unmask heart rate-independent effects of β-blockers on pulse wave reflections

Clinical Research in Cardiology > Ausgabe 6/2014
Ulrich Fischer-Rasokat, Jörg Honold, Denise Lochmann, Christoph Liebetrau, Jürgen Leick, Christian Hamm, Stephan Fichtlscherer, Helge Möllmann, Ioakim Spyridopoulos



Prior studies suggest that β-blockers lead to increased pulse wave reflections, thereby negating the blood pressure lowering effects on cardiovascular mortality. Parts of these effects may be induced by the heart rate reduction under β-blockade. The aim of this study was to unmask heart rate-independent effects of β-blockade on pulse wave reflections by switching therapy from β-blockers to ivabradine, an I f channel inhibitor without impact on systemic hemodynamics.


14 male patients (age 61 ± 3 years, LVEF 62 ± 1 %) with arterial hypertension and coronary artery disease (CAD) under chronic β-blocker therapy at moderate dosage and additional renin-angiotensin system-blocking therapy were included. We determined radial augmentation index (rAI) by radial applanation tonometry in patients under β-blockade both at rest and during early recovery after exercise. β-Blockers were then replaced by ivabradine. Six weeks later, patients were re-tested at rest and after exercise under ivabradine therapy.


Mean heart rate (68 ± 3 vs. 63 ± 3 bpm; p = ns) and resting mean arterial pressure (98 ± 2 vs. 98 ± 2 mmHg; p = ns) were not different between β-blocker or ivabradine therapy, respectively. The rAI remained unchanged after switching therapy from β-blocker to ivabradine (86 ± 2 vs. 84 ± 4 %; p = ns). Post exercise, the rAI revealed an identical decrease in both groups (−7.2 ± 2.4 vs. −5.4 ± 2.5 %, p = ns). The increase in heart rate between resting conditions and early recovery post exercise was inversely correlated with the decrease of rAI under β-blockade (r = −0.70; p < 0.01) and showed a trend towards correlation under ivabradine (r = −0.52; p = 0.07).


In men at the age of 60 years and CAD, β-blockade does not exert heart rate-independent, pleiotropic effects on peripheral pulse wave reflections, both at rest or after exercise. Our results fit well within recent studies, demonstrating the fundamental influence of heart rate on rAI.

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