CLINICAL RESEARCH
Ximelagatran versus warfarin forstroke prevention in patientswith nonvalvular atrial fibrillation
SPORTIF ii: a dose-guiding, tolerability, and safety study
Palle Petersen, MD, DMSc, FCCP*,*,
Margaretha Grind, MD, PhD ,
John Adler, MSc SPORTIF II Investigators
* Department of Neurology, University State Hospital, Rigshospitalet, Copenhagen, Denmark
Department of Clinical Science and Medicine, AstraZeneca R&D Charnwood, Loughborough, United Kingdom
Department of Biostatistics, AstraZeneca R&D, Mölndal, Sweden
Manuscript received September 17, 2002;
revised manuscript received December 20, 2002,
accepted December 27, 2002.
* Reprint requests and correspondence: Dr. Palle Petersen, Department of Neurology, University State Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
pape{at}rh.dk
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 NVAF patients 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.
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Abbreviations and Acronyms
| | AE | = adverse event | | AF | = atrial fibrillation | | aPTT | = activated partial thromboplastin time | | Fe-Hb | = fecal hemoglobin | | INR | = International Normalized Ratio | | NVAF | = nonvalvular atrial fibrillation | | S-ALAT | = S-alanine aminotransferase | | SPORTIF | = Stroke Prevention by ORal Thrombin Inhibitor in atrial Fibrillation trial | | TIA | = transient ischemic attack | | U-Hb | = urinary erythrocytes (hemoglobin) |
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