Ivabradine therapy to unmask heart rate-independent effects of [beta]-blockers on pulse wave reflections

• Published in: Clinical research in cardiology Vol. 103; no. 6; p. 487
• Main Authors: Fischer-rasokat, Ulrich, Honold, Jörg, Lochmann, Denise, Liebetrau, Christoph, Leick, Jürgen, Hamm, Christian, Fichtlscherer, Stephan, Möllmann, Helge, Spyridopoulos, Ioakim
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer Nature B.V 01.06.2014
• ISSN: 1861-0684; 1861-0692
• DOI: 10.1007/s00392-014-0679-1

Prior studies suggest that [beta]-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 [beta]-blockade. The aim of this study was to unmask heart rate-independent effects of [beta]-blockade on pulse wave reflections by switching therapy from [beta]-blockers to ivabradine, an I ^sub 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 [beta]-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 [beta]-blockade both at rest and during early recovery after exercise. [beta]-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 [beta]-blocker or ivabradine therapy, respectively. The rAI remained unchanged after switching therapy from [beta]-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 [beta]-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, [beta]-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.[PUBLICATION ABSTRACT]