Search

We investigated the hemodynamic effects of 2 short‐acting β1‐blockers, landiolol and esmolol, in the continuous presence of dobutamine in a prospective, single‐center, randomized, crossover study in 16 healthy White volunteers. Dobutamine was infused at a rate sufficient to increase the heart rate by at least 30 beats per minute, followed by a 60‐minute infusion of 50 μg/kg/min esmolol or 10 μg/kg/min landiolol on top of the unchanged dobutamine infusion. Concentrations of β‐blockers and their metabolites in blood, heart rate, and blood pressure were followed for 180 minutes. Landiolol reduced the dobutamine‐induced heart rate and blood pressure increases better than esmolol. After discontinuation of β‐blocker administration, heart rate recovered swiftly to preinfusion values in both study arms. Systolic and diastolic blood pressure recovered partially after landiolol but showed a continued reduction after esmolol. No serious adverse events were observed. The heart rate effect is characteristic for β‐blockers, whereas the blood pressure effects are likely due to direct and indirect β‐blocker effects as well as influences on various ion channels. This may explain why landiolol that is devoid of effects on renin and sodium, calcium, and potassium channels behaves different from esmolol with respect to blood pressure recovery. [ABSTRACT FROM AUTHOR]

Summary: Anagrelide is an established treatment option for essential thrombocythaemia (ET). A prolonged release formulation was developed with the aim of reducing dosing frequency and improving tolerability, without diminishing efficacy. This multicentre, randomized, double blind, active‐controlled, non‐inferiority trial investigated the efficacy, safety and tolerability of anagrelide prolonged release (A‐PR) over a reference product in high‐risk ET patients, either anagrelide‐naïve or ‐experienced. In a 6 to 12‐week titration period the individual dose for the consecutive 4‐week maintenance period was identified. The primary endpoint was the mean platelet count during the maintenance period (3 consecutive measurements, day 0, 14, 28). Of 112 included patients 106 were randomized. The mean screening platelet counts were 822 × 109/l (95% confidence interval (CI) 707–936 × 109/l) and 797 × 109/l (95% CI 708–883 × 109/l) for A‐PR and the reference product, respectively. Both treatments effectively reduced platelet counts, to mean 281 × 109/l for A‐PR (95% CI 254–311) and 305 × 109/l (95% CI 276–337) for the reference product (P < 0·0001, for non‐inferiority). Safety and tolerability were comparable between both drugs. The novel prolonged‐release formulation was equally effective and well tolerated compared to the reference product. A‐PR provides a more convenient dosing schedule and will offer an alternative to licensed immediate‐release anagrelide formulations. [ABSTRACT FROM AUTHOR]