AIMS: Myocardial 5-HT(4) serotonin (5-HT) receptors are increased and activated in heart failure (HF). Blockade of 5-HT(4) receptors reduced left ventricular (LV) remodelling in HF rats. We evaluated the effect of piboserod, a potent, selective, 5-HT(4) serotonin receptor antagonist, on LV function in patients with HF. METHODS AND RESULTS: This was a prospective, double-blind, parallel group trial in patients with NYHA class II-IV HF and LV ejection fraction (EF) < or =0.35. Patients receiving standard HF treatment were randomized to placebo (n = 70) or piboserod 80 mg (n = 67) for 24 weeks including 4 weeks up titration. The primary endpoint was LVEF measured by cardiac magnetic resonance imaging (MRI). Secondary endpoints were LV volumes, N-terminal pro-brain natriuretic peptide, norepinephrine, quality of life, and 6 min walk test. Piboserod significantly increased LVEF by 1.7% vs. placebo (CI 0.3, 3.2, P = 0.020), primarily through reduced end-systolic volume from 165 to 158 mL (P = 0.060). There was a trend for greater increase in LVEF (2.7%, CI -1.1, 6.6, P = 0.15) in a small subset of patients not on chronic beta-blocker therapy. There was no significant effect on neurohormones, quality of life, or exercise tolerance. Patients on piboserod reported more adverse events, but numbers were too small to identify specific safety issues. CONCLUSION: Although patients with chronic HF had a small but significant improvement in LVEF when treated with piboserod for 24 weeks, the result was not reflected in significant changes in other efficacy parameters, and its clinical relevance remains uncertain.
RCT Entities:
AIMS: Myocardial 5-HT(4) serotonin (5-HT) receptors are increased and activated in heart failure (HF). Blockade of 5-HT(4) receptors reduced left ventricular (LV) remodelling in HF rats. We evaluated the effect of piboserod, a potent, selective, 5-HT(4) serotonin receptor antagonist, on LV function in patients with HF. METHODS AND RESULTS: This was a prospective, double-blind, parallel group trial in patients with NYHA class II-IV HF and LV ejection fraction (EF) < or =0.35. Patients receiving standard HF treatment were randomized to placebo (n = 70) or piboserod 80 mg (n = 67) for 24 weeks including 4 weeks up titration. The primary endpoint was LVEF measured by cardiac magnetic resonance imaging (MRI). Secondary endpoints were LV volumes, N-terminal pro-brain natriuretic peptide, norepinephrine, quality of life, and 6 min walk test. Piboserod significantly increased LVEF by 1.7% vs. placebo (CI 0.3, 3.2, P = 0.020), primarily through reduced end-systolic volume from 165 to 158 mL (P = 0.060). There was a trend for greater increase in LVEF (2.7%, CI -1.1, 6.6, P = 0.15) in a small subset of patients not on chronic beta-blocker therapy. There was no significant effect on neurohormones, quality of life, or exercise tolerance. Patients on piboserod reported more adverse events, but numbers were too small to identify specific safety issues. CONCLUSION: Although patients with chronic HF had a small but significant improvement in LVEF when treated with piboserod for 24 weeks, the result was not reflected in significant changes in other efficacy parameters, and its clinical relevance remains uncertain.
Authors: Trond Brattelid; Eirik Qvigstad; Lise R Moltzau; Silje V S Bekkevold; Dagny L Sandnes; Jon Arne K Birkeland; Tor Skomedal; Jan-Bjørn Osnes; Ivar Sjaastad; Finn Olav Levy Journal: PLoS One Date: 2012-09-20 Impact factor: 3.240
Authors: Faraz Afzal; Eirik Qvigstad; Jan Magnus Aronsen; Lise Román Moltzau; Ivar Sjaastad; Tor Skomedal; Jan-Bjørn Osnes; Finn Olav Levy Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2011-09-08 Impact factor: 3.000
Authors: Ulrich Gergs; Timo Gerigk; Jonas Wittschier; Constanze T Schmidbaur; Clara Röttger; Mareen Mahnkopf; Hanna Edler; Hartmut Wache; Joachim Neumann Journal: Biomedicines Date: 2021-05-18