OBJECTIVES: We sought to compare the tolerability and safety of three fixed doses of ximelagatran versus warfarin in patients with nonvalvular atrial fibrillation (NVAF). BACKGROUND: Anticoagulants such as warfarin lower the risk of stroke in patients with NVAF. Ximelagatran is a novel, oral direct thrombin inhibitor with predictable pharmacokinetics and no known food or pharmacokinetic drug interactions. METHODS: This was a 12-week, randomized, parallel-group, dose-guiding study of NVAFpatients with at least one additional risk factor for stroke. The primary end point was the number of thromboembolic events and bleedings. Three groups received ximelagatran (n = 187) at 20, 40, or 60 mg twice daily, given in a double-blind fashion, without routine coagulation monitoring. In a fourth group, warfarin (n = 67) was managed and monitored according to normal routines, aiming for an International Normalized Ratio of 2.0 to 3.0. RESULTS: A total of 254 patients received study drug. One ischemic stroke (nonfatal) and one transient ischemic attack (TIA) occurred in the ximelagatran group. Two TIAs occurred in the warfarin group. No major bleeds were observed in the ximelagatran group. One major bleed occurred in a warfarin-treated patient. The number of minor and multiple minor bleeds was low, but there was a slight increase by ximelagatran dose. The 60-mg dose resulted in the same number of bleeding events as that with warfarin. S-alanine aminotransferase was increased in eight patients (4.3%) taking ximelagatran, but normalized with continuous treatment or cessation of the drug. CONCLUSIONS: Fixed oral doses of ximelagatran up to 60 mg twice daily were well tolerated, without the need for dose adjustment or coagulation monitoring.
RCT Entities:
OBJECTIVES: We sought to compare the tolerability and safety of three fixed doses of ximelagatran versus warfarin in patients with nonvalvular atrial fibrillation (NVAF). BACKGROUND: Anticoagulants such as warfarin lower the risk of stroke in patients with NVAF. Ximelagatran is a novel, oral direct thrombin inhibitor with predictable pharmacokinetics and no known food or pharmacokinetic drug interactions. METHODS: This was a 12-week, randomized, parallel-group, dose-guiding study of NVAFpatients with at least one additional risk factor for stroke. The primary end point was the number of thromboembolic events and bleedings. Three groups received ximelagatran (n = 187) at 20, 40, or 60 mg twice daily, given in a double-blind fashion, without routine coagulation monitoring. In a fourth group, warfarin (n = 67) was managed and monitored according to normal routines, aiming for an International Normalized Ratio of 2.0 to 3.0. RESULTS: A total of 254 patients received study drug. One ischemic stroke (nonfatal) and one transient ischemic attack (TIA) occurred in the ximelagatran group. Two TIAs occurred in the warfarin group. No major bleeds were observed in the ximelagatran group. One major bleed occurred in a warfarin-treated patient. The number of minor and multiple minor bleeds was low, but there was a slight increase by ximelagatran dose. The 60-mg dose resulted in the same number of bleeding events as that with warfarin. S-alanine aminotransferase was increased in eight patients (4.3%) taking ximelagatran, but normalized with continuous treatment or cessation of the drug. CONCLUSIONS: Fixed oral doses of ximelagatran up to 60 mg twice daily were well tolerated, without the need for dose adjustment or coagulation monitoring.
Authors: Regina E Roller; Bernhard Iglseder; Peter Dovjak; Monika Lechleitner; Ulrike Sommeregger; Ursula Benvenuti-Falger; Ronald Otto; Birgit Böhmdorfer; Markus Gosch Journal: Wien Med Wochenschr Date: 2010-06
Authors: Ulf G Eriksson; Susanne Johansson; Per-Ola Attman; Henrik Mulec; Lars Frison; Gunnar Fager; Ola Samuelsson Journal: Clin Pharmacokinet Date: 2003 Impact factor: 6.447
Authors: Karin Wåhlander; Maria Eriksson-Lepkowska; Lars Frison; Gunnar Fager; Ulf G Eriksson Journal: Clin Pharmacokinet Date: 2003 Impact factor: 6.447
Authors: Eva Bredberg; Tommy B Andersson; Lars Frison; Annelie Thuresson; Susanne Johansson; Maria Eriksson-Lepkowska; Marita Larsson; Ulf G Eriksson Journal: Clin Pharmacokinet Date: 2003 Impact factor: 6.447