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| |  Piboserod Improves Left-Ventricular Function in Patients With Symptomatic Heart Failure: Presented at HF2008 By Chris Berrie MILAN, Italy -- June 18, 2008 -- The 5-HT4 serotonin receptor antagonist piboserod provides small but significant improvements compared with placebo in left-ventricular ejection fraction (LVEF) in patients with symptomatic heart failure (HF) receiving optimised standard treatment, according to a multicentre, prospective, randomised, double-blind, placebo-controlled, parallel-group trial. The concept behind this novel approach to HF treatment is that expression of 5-HT4 receptors and plasma levels of serotonin have been shown to be increased in patients with heart failure, the researchers said during a presentation here on June 16 at the Heart Failure 2008 (HF2008) Congress. Principal investigator John K. Kjekshus, MD, PhD, Department of Cardiology, Rikshospitalet University Hospital, Oslo, Norway, said, "As beta-adrenergic receptors are down-regulated in heart failure and [the 5-HT4 serotonin] receptor is up-regulated, we thought that inhibition might be beneficial." To evaluate the safety and effects on LVEF of piboserod treatment versus placebo when administered in addition to optimised standard therapies in patients with stable HF, Dr. Kjekshus and colleagues evaluated 137 patients with LVEF <=35% who were treated for 24 weeks and were assessed for LVEF by magnetic resonance imaging MRI. The researchers randomised 70 patients to placebo and 67 patients to piboserod. All baseline characteristics were well matched between the treatment groups, and all patients received optimised standard therapies. Piboserod treatment was up-titrated from 20 mg to 40 mg after 2 weeks and to the 80-mg maintenance dose after 4 weeks. At 24 weeks, as compared with placebo, piboserod caused a small but significant 1.7% benefit over placebo in change in LVEF (-0.3% vs 1.4%; P = .02). For the small subset of patients not receiving beta-blocker therapy, there was a trend for slightly larger benefit with piboserod (2.7%; P = .15). Further trends towards improvements with piboserod were seen for end-systolic volume index (-1.1 vs -4.2 mL/m2; P = .0687) and systolic blood pressure (3.3 vs -1.4 mm Hg; P = .075). There were no significant changes or specific trends seen between active treatment and placebo for the range of secondary endpoints. In the safety analysis for serious adverse events, the researchers found that the piboserod group had 22 events in 17 patients, compared with 7 events in 5 patients in the placebo group, a significant difference. Similarly, more patients discontinued treatment in the active arm (8 vs 3). Thus, the results confirm the data from animal studies, which showed improvements -- although small ones -- in left-ventricular function with piboserod.
[Presentation title: The Effect of Piboserod, a 5-HT4 Serotonin Receptor Antagonist, on Left Ventricular Function in Patients With Symptomatic Heart Failure. Abstract P730]
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