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

Objectives: 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). Methods: During diagnostic coronary angiography (baseline), twenty-one patients with stable CAD under-went 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 (5mg 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. Results: Heart rate was significantly lower after treatment with ivabradine (78 +/- 14bpm 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). Conclusions: 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. (C) 2010 Elsevier Ireland Ltd. All rights reserved.