The effect of heart rate reduction by ivabradine on collateral function in patients with chronic stable coronary artery disease

Gloekler, Steffen; Traupe, Tobias; Stoller, Michael; Schild, D; Steck, Hélène; Khattab, Ahmed A.; Vogel, Rolf; Seiler, Christian

doi:10.1136/heartjnl-2013-304880

Cited by 51 publications

(39 citation statements)

References 23 publications

(21 reference statements)

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“…Diastolic coronary flow was pharmacologically increased in patients with CAD for 6 mo, resulting in a significant increase in coronary flow index compared with placebo control. The treatment group also demonstrated a decrease in the area of the ischemic zone, as indicated by ECG ST segment shift (18).…”

mentioning

confidence: 86%

“…However, prolonged increased FSS achieved by arteriovenous shunt results in continued enlargement of collateral vessels (13,37,44,45). Recently, compelling clinical evidence for the role of FSS in arteriogenesis was provided by Gloekler et al (18). Diastolic coronary flow was pharmacologically increased in patients with CAD for 6 mo, resulting in a significant increase in coronary flow index compared with placebo control.…”

mentioning

confidence: 99%

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Fluid shear stress upregulates placental growth factor in the vessel wall via NADPH oxidase 4

Rashdan

Lloyd

2015

American Journal of Physiology-Heart and Circulatory Physiology

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confidence: 86%

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confidence: 99%

Fluid shear stress upregulates placental growth factor in the vessel wall via NADPH oxidase 4

Rashdan

Lloyd

2015

American Journal of Physiology-Heart and Circulatory Physiology

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“…In addition, ivabradine increases coronary flow reserve and collateral perfusion, promoting the development of coronary collaterals and maintaining endothelial function in patients with chronic stable angina 47,48 . The antianginal effects of ivabradine have been documented in several randomized clinical trials against placebo, various active comparators, and in addition to β-blockers, as well as in unselected studies reflecting routine clinical practice 29,49 .…”

Section: Key Points For Nicorandilmentioning

confidence: 99%

“…Subsequently, in a double-blind, placebo-controlled, crossover study conducted in women with effort angina but no obstructive coronary artery disease, ranolazine produced no significant benefits except in some patients with impaired coronary flow reserve 65 . Analogously, ivabradine has been shown to improve coronary collateral flow and coronary flow reserve in patients with microvascular angina 47,48 . The effects of ivabradine were superior to those of bisoprolol, despite similar degrees of heart-rate reduction 48 .…”

Section: Microvascular Anginamentioning

confidence: 99%

A 'diamond' approach to personalized treatment of angina

et al. 2017

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Chronic stable angina pectoris is the most prevalent symptomatic manifestation of ischaemic heart disease, and its management is a priority (BOX 1). Current clinical guidelines recommend antianginal therapy to control symptoms, before considering coronary artery revasculariza tion [1][2][3][4] . However, revascularization by either percutaneous coronary angioplasty or CABG surgery is indicated in patients who have significant artery steno sis (50% left main narrowing or proximal three-vessel disease) to reduce myocardial ischaemia and its adverse clinical manifestation. Antianginal agents are approved by documenting that they improve total exercise duration, together with a reduction in daily frequency of chronic stable angina compared with placebo and/or equivalence to an active comparator. Cardiovascular outcomes, although highly advocated, are not a pre requisite for regulatory approval. None of the antianginal drugs has been proved to reduce cardiovascular mortality or the rate of myocardial infarction. When patients are optimally treated, mortality for chronic stable angina is low, which might explain why all trials designed to improve prognosis have been negative. Guidelines recom mend a first-choice and a second-choice approach, based more on tradition and expert opinion, rather than evidence. This categorical approach has been questioned in the past couple of years 5-8 . Newer antianginal drugs, which are classified as second choice, have more evidence-based clinical data that are more contemporary to support their use than is available for the traditional first-choice drugs. Equally, the often-needed combin ation of double or triple therapy is based on expert opinion and not related to the underlying pathophysio logy. What constitutes optimal antianginal treatment, therefore, varies considerably between countries, and the majority of doctors treat their patients according to their own preconceptions.A group of experts with experience and interest in chronic stable angina met at the University of Ferrara, Italy, to discuss an individualized approach to medical treatment of chronic stable angina, on the basis E X P E RT C O N S E N S U S D O C U M E N TA 'diamond' approach to personalized treatment of angina Abstract | In clinical guidelines, drugs for symptomatic angina are classified as being first choice (β-blockers, calcium-channel blockers, short-acting nitrates) or second choice (ivabradine, nicorandil, ranolazine, trimetazidine), with the recommendation to reserve second-choice medications for patients who have contraindications to first-choice agents, do not tolerate them, or remain symptomatic. No direct comparisons between first-choice and second-choice treatments have demonstrated the superiority of one group of drugs over the other. Meta-analyses show that all antianginal drugs have similar efficacy in reducing symptoms, but provide no evidence for improvement in survival. The newer, second-choice drugs have more evidence-based clinical data that are more contemporary than is available for tr...

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“…23 Recently, the first study of the effect of ivabradine on the coronary collateral circulation in humans has been published. The results of this first-time clinical, placebocontrolled randomized study show that ivabradine improves coronary collateral flow index in patients with stable coronary artery disease and diminishes electrocardiographic signs of ischaemia 24 ( Figure 6). These data also demonstrate the differential advantage of ivabradine confirmed by the lack of data on improvement of collateral circulation with b-blockers.…”

Section: Coronary Flow Reservementioning

confidence: 94%

The role of ivabradine in improving myocardial perfusion, adding to the antianginal benefits

Vardas

Skalidis

2015

Eur Heart J Suppl

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The most common cause of oxygen demand/supply mismatch is atherosclerotic narrowing of the coronary artery, resulting in decreased coronary blood flow. However, endothelial dysfunction and/or microvascular dysfunction may be responsible for myocardial ischaemia and importantly may often coexist in patients with angina. Coronary flow reserve reflects the functional capacity of coronary circulation to adapt to the blood demand during increased cardiac work. In addition, coronary flow reserve predicts long-term adverse cardiovascular outcome. Therefore, a clear understanding of myocardial perfusion pathophysiology and a knowledge of the antianginal-anti-ischaemic drugs effect on coronary circulation are crucial for the judicious use of medications for the treatment of angina patients with coronary artery disease. This article discusses the role of ivabradine in improvement of myocardial perfusion based on data drawn from relevant preclinical and clinical investigations. Experimental data suggest that heart rate reduction with ivabradine causes greater increase in duration of diastolic perfusion time and coronary flow compared with b-blockade due to absence of impairing of left ventricular contractility and coronary vasomotion. In consequence, the full benefits of heart rate reduction for improved coronary perfusion could be realized with ivabradine. Following experimental data, clinical studies demonstrated anti-ischaemic and antianginal efficacy of ivabradine in patients with stable coronary artery disease. These clinical benefits have been supported by recent clinical data on improvement of coronary flow reserve, and coronary collateral circulation with ivabradine supports the role of ivabradine as an important anti-ischaemic and antianginal agent in patients with angina in addition to other recommended therapies or revascularization.

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The effect of heart rate reduction by ivabradine on collateral function in patients with chronic stable coronary artery disease

Abstract: NCT01039389.

Cited by 51 publications

References 23 publications

Fluid shear stress upregulates placental growth factor in the vessel wall via NADPH oxidase 4

Fluid shear stress upregulates placental growth factor in the vessel wall via NADPH oxidase 4

A 'diamond' approach to personalized treatment of angina

The role of ivabradine in improving myocardial perfusion, adding to the antianginal benefits

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