Ivabradine improves coronary flow reserve in patients with stable coronary artery disease

Cardiology Department, University Hospital of Heraklion, and Biostatistics Lab, University of Crete, Crete, Greece.
Atherosclerosis (Impact Factor: 3.99). 12/2010; 215(1):160-5. DOI: 10.1016/j.atherosclerosis.2010.11.035
Source: PubMed


Although treatment with ivabradine reduces the incidence of hospital admissions for myocardial infarction and coronary revascularisation, there are no data concerning its effect on coronary circulation. The purpose of this study was to assess the effects of ivabradine on coronary flow velocity and flow reserve (CFR) in patients with stable coronary artery disease (CAD).
During diagnostic coronary angiography (baseline), twenty-one patients with stable CAD underwent coronary flow velocity measurements (APV cm/s) in a non-culprit vessel, using a Doppler guidewire, at rest (r) and after adenosine administration to achieve maximal hyperaemia (h). During programmed coronary intervention in the culprit vessel, the same measurements were repeated one week after treatment with ivabradine (5 mg twice daily), both at the intrinsic heart rate and at a paced heart rate identical to that before treatment. CFR was defined as h-APV/r-APV.
Heart rate was significantly lower after treatment with ivabradine (78±14 bpm vs 65±9 bpm, p<0.001). Also, a reduction of r-APV (17.0±5.5 vs 19.7±7.6, p=0.003) and augmentation of h-APV (57.9±17.8 vs 53.5±21.4, p=0.009) leading to CFR improvement (3.51±0.81 vs 2.78±0.61, p<0.001) were observed. During pacing, although r-APV reverted to values similar to those before treatment (20.0±6.5 vs 19.7±7.6, p=NS), a sustained improvement in h-APV was observed (59.5±19.7 vs 53.5±21.4, p=0.007) and CFR remained higher than before treatment (3.04±0.66 vs 2.78±0.61, p<0.001).
Ivabradine treatment significantly improves hyperaemic coronary flow velocity and CFR in patients with stable CAD. These effects remain even after heart rate correction indicating improved microvascular function.

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Available from: Emmanouil I Skalidis, Aug 20, 2014
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    • "An interesting study on the pleiotropic effects of ivabradine comes from Skalidis et al.45 These authors demonstrated that a reduction in heart rate by means of ivabradine was able to improve coronary blood flow at rest. "
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    ABSTRACT: Elevated heart rate could negatively influence cardiovascular risk in the general population. It can induce and promote the atherosclerotic process by means of several mechanisms involving endothelial shear stress and biochemical activities. Furthermore, elevated heart rate can directly increase heart ischemic conditions because of its skill in unbalancing demand/supply of oxygen and decreasing the diastolic period. Thus, many pharmacological treatments have been proposed in order to reduce heart rate and ameliorate the cardiovascular risk profile of individuals, especially those suffering from coronary artery diseases (CAD) and chronic heart failure (CHF). Ivabradine is the first pure heart rate reductive drug approved and currently used in humans, created in order to selectively reduce sinus node function and to overcome the many side effects of similar pharmacological tools (ie, β-blockers or calcium channel antagonists). The aim of our review is to evaluate the role and the safety of this molecule on CAD and CHF therapeutic strategies.
    Full-text · Article · Jun 2014 · Drug Design, Development and Therapy
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    • "It may also be explained by the prolonged diastolic period (per cardiac beat and per minute). Moreover, we can speculate that the endothelial-dependent vasodilatation expressed by the significant changes observed in the photoplethysmographic curves in peripheral and coronary territories plays an important role in improving coronary blood reserve as has already been described [35] [36], and flow velocity may have a direct effect on coronary vessels and reduced ventricular wall tension, with improvement of ventricular relaxation [14], added to diminished right ventricular diastolic diameter with significant reduction of arterial pulmonary pressure, which probably reflects improved coronary perfusion pressure (aortic mean pressure/coronary sinus ratio). "
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    ABSTRACT: Background. Ivabradine is an If ion current inhibitor that has proved to reduce mortality in patients with systolic heart failure by slowing heart rate without decreasing myocardial contractility. Photoplethysmography is a simple, low-cost optical technique that can evaluate vascular function and detect changes in blood flow, pulse, and swelling of tissular microvascular space. Objective. To evaluate the effect of ivabradine on endothelial function by photoplethysmography in diastolic and right heart failure patients. Methodology. 15 patients were included (mean age of 78.1 ± 9.2 years) with optimally treated diastolic and right heart failure. They underwent photoplethysmography before and after induced ischemia to evaluate the wave blood flow on the finger, using the maximum amplitude time/total time (MAT/TT) index. Two measurements were made before and after oral Ivabradine (mean 12.5 mg a day during 6 months of followup). Results. In the study group, the MAT/TT index was 29.1 ± 2.2 versus 24.3 ± 3.2 (P = 0.05) in basal recording and 30.4 ± 2.1 versus 23.3 ± 2.9 (P = 0.002), before versus after ischemia and before versus after Ivabradine intervention, respectively. Conclusions. Ivabradine administration improves endothelial function (shear stress) in diastolic and right heart failure patients.
    Full-text · Article · Oct 2013
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    • "Skalidis et al. [46] assessed the effect of ivabradine (5 mg twice daily) on coronary blood flow velocity and coronary flow reserve (CFR) in patients with stable CAD (n = 21). Coronary blood flow was assessed invasively using intracoronary Doppler measurements at baseline and after 1 week of ivabradine treatment. "
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    ABSTRACT: Heart rate is an important contributor in the pathophysiology of both coronary artery disease (CAD) and heart failure (HF). Ivabradine is an anti-anginal and anti-ischaemic agent, which selectively and specifically inhibits the I f current in the sino-atrial node and provides pure heart rate reduction without altering other cardiac parameters, including conduction, and without directly affecting other haemodynamic parameters. It is approved for the treatment of CAD and HF. This article summarises the pharmacological properties, pharmacokinetics, clinical efficacy and tolerability of ivabradine in the treatment of CAD and HF, and presents evidence demonstrating that the pharmacological and clinical properties and clinical efficacy of ivabradine make it an important therapeutic choice for patients with stable CAD or HF. The positive effect of ivabradine on angina pectoris symptoms and its ability to reduce myocardial ischemia make it an important agent in the management of patients with stable CAD or chronic HF. Further studies are underway to add to the already robust evidence of ivabradine for the prevention of cardiovascular events in patients with CAD but without clinical HF. The SIGNIFY (Study assessInG the morbidity–mortality beNefits of the I f inhibitor ivabradine in patients with coronarY artery disease) trial includes patients with stable CAD and an LVEF above 40 %, with no clinical sign of HF, and is investigating the long-term effects (over a period of 48 months) of ivabradine in a large study population. So far, this study has included more than 19,000 patients from 51 countries.
    Full-text · Article · Sep 2013 · Drugs
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