A randomized, double-blind, placebo-controlled, phase III study of the short-acting β1-adrenergic receptor blocker landiolol hydrochloride for coronary computed tomography angiography in Japanese patients with suspected ischemic cardiac disease

Abstract

Objectives and background: The objective of this study was to investigate the image quality-improving and heart rate-lowering effects of landiolol hydrochloride (a short-acting β1-adrenergic receptor blocker) on coronary computed tomography angiography (CCTA). During CCTA, β-adrenergic receptor blockers have been commonly used to lower heart rate and improve image quality.

Methods: A total of 258 subjects suspected of having ischemic cardiac disease and requiring CCTA were randomized to either a landiolol hydrochloride 0.125 mg/kg group or placebo group to study the efficacy and safety of landiolol hydrochloride in a multicenter, double-blind, randomized parallel study. The primary endpoint was the diagnosable proportion (proportion of subjects whose coronary stenosis was diagnosable).

Results: The diagnosable proportions about the reconstruction images at mid-diastole were 68.2 and 38.2 % in the landiolol hydrochloride and placebo group, respectively, indicating significant superiority of landiolol hydrochloride over placebo (p < 0.0001). The diagnosable proportions about the optimal reconstruction images were 81.4 and 54.2 % in the landiolol hydrochloride and placebo group, respectively, indicating significant superiority of landiolol hydrochloride over placebo (p < 0.0001). The mean heart rate-lowering effect was first observed soon after administration of landiolol hydrochloride, was most marked at 3-5 min, and disappeared 30 min after completion of administration. The mean heart rate-lowering proportion at that time was -19.1 ± 8.1 % and -5.9 ± 9.7 % in the landiolol hydrochloride and placebo groups, respectively, showing a significantly higher proportion in the landiolol hydrochloride group.

Conclusions: Landiolol hydrochloride was confirmed to significantly and rapidly lower heart rate after intravenous injection, suggesting that it is a safe and useful agent for improving the image quality of CCTA.

Fig. 1

Time flow of study drug administration. The study drug was administered over 1 min, ≥5 min after nitrate drug administration. CCTA coronary computed tomography angiography, CT computed tomography

Fig. 2

Flow diagram of subjects

Fig. 3

Mean ± standard deviation changes in heart rate. Rotation speed of the X-ray tube was set at the maximum speed for each type of computed tomography equipment. CCTA coronary computed tomography angiography, CT computed tomography, *p < 0.05 vs. placebo (t test)

Fig. 4

Mean ± standard deviation changes in blood pressure. Mean blood pressure showed a significant difference between the two groups, but the lowering proportion was limited, as shown in Table 3. CCTA coronary computed tomography angiography, CT computed tomography, *p < 0.05 vs. placebo (t test)

Fig. 5

Relationship between diagnosable proportion and heart rate. There was a positive correlation between the diagnosable proportion and heart rate