A Randomized, Double-Blind, Placebo-Controlled, Phase III Study of the Short-Acting β(1)-Adrenergic Receptor Blocker Landiolol Hydrochloride for Coronary Computed Tomography Angiography in Japanese Patients with Suspected Ischemic Cardiac Disease

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 β(1)-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.