Incremental value and safety of oral ivabradine for heart rate reduction in computed tomography coronary angiography

Abstract

Background

Heart rate (HR) reduction is essential to achieve optimal image quality and diagnostic accuracy with computed tomography coronary angiography (CTCA). Administration of ivabradine could be an attractive alternative to beta-blockade to reduce HR.

Methods

One-hundred-twenty-three patients referred for CTCA were prospectively enrolled. Patients were divided in two groups depending on the absence or presence of chronic beta-blockade treatment. Within the two groups patients were randomized to either no additional premedication or oral ivabradine for 5 days prior to CTCA. In presence of chronic beta-blockade therapy it was shifted to atenolol 50 mg twice a day for 5 days prior to CTCA. HR and blood pressure were assessed at admission (T0), immediately before CTCA (T1) and during CTCA (T2). The target HR was < 65 bpm.

Results

Ivabradine significantly reduced HR during CTCA. Mean relative HR reduction was 15% for controls, 12% for chronic beta-blockade, 19% for ivabradine and 24% for both chronic beta-blockade and ivabradine at T2 (p for trend < 0.001). The rate of patients who reached the target HR at T2 was 83% in controls, 71% with chronic beta-blockade, 97% with ivabradine and 97% with both (p for trend < 0.05). The percentage of patients that needed additional IV beta-blockade at T1 decreased from 69% to 40% with ivabradine and 30% with both (p for trend < 0.05).

Conclusions

Ivabradine is safe and effective in increasing the rate of patients at target HR and in reducing the need for additional IV beta-blockade in patients referred for CTCA.

Introduction

Computed tomography coronary angiography (CTCA) is an emerging non-invasive tool for the diagnosis of coronary artery disease [1]. Its main ability is to assess coronary artery lumen and vessel wall resulting in a detailed analysis of stenosis severity as well as plaque burden and composition. Moreover CTCA is the only technique able to visualize coronary lumen in case of total occlusion, yielding decisive information before attempting Coronary Angioplasty [2]. Most of the studies on CTCA showed a high negative predictive value, ranging from 93% to 100%, in the ruling-out of significant coronary stenosis [3], [4], [5], [6]. The weighted mean sensitivity and specificity for the detection of coronary artery stenosis were respectively 93% and 96% [7]. CTCA is effective in evaluating coronary by-pass because of favorable anatomic position while imaging of implanted coronary stents is more challenging, mainly because of technical restriction [8]. On the other hand, the procedure leads to radiation exposure and contrast material injury; however, the former has being reduced by the technological improvement and the latter can be reduced by an adequate hydration on the patient undergoing CTCA [9], [10]. Importantly, to achieve optimal diagnostic accuracy, adequate image quality is mandatory. In this respect, a low and stable heart rate (HR) is an important prerequisite, whereas an increase in HR is associated with an almost linear deterioration of image quality and diagnostic accuracy [11], [12], [13]. Accordingly, to minimize coronary artery motion artifacts and optimize image quality, an HR < 65 bpm is required [3], [14]. To achieve HR reduction, beta-blocking medication or calcium-antagonists are routinely administered prior to the CTCA examination. However, several studies have reported that despite the use of aggressive beta-blocking strategies, target HR < 65 bpm cannot be achieved in all patients [15], [16], [17].

To improve HR control prior to CTCA, the use of ivabradine, a novel HR lowering agent, may be an attractive option [18], [19]. Ivabradine is a highly selective and specific inhibitor of the I_f current, which contributes to sinus node pacemaker activity. Notably, ivabradine lowers HR at concentrations that do not affect other cardiac ionic currents [18]. As a result, ivabradine has no other direct cardiovascular effects [20].

Although the pharmacological properties of ivabradine have been widely described, no studies have specifically addressed the efficacy and safety of oral administration of ivabradine in patients undergoing CTCA, so far.

The aim of the study was to assess whether oral premedication with ivabradine in patients referred for CTCA is safe and can significantly increase the rate of patients achieving the target HR (< 65 bpm) during the investigation as compared to chronic beta-blockade. Secondly, we assessed the reduction in the need of additional IV (intravenous) beta-blockers administration due to the use of oral ivabradine as compared to chronic beta-blockade.