Clinical research
Ximelagatran versus warfarin forstroke prevention in patientswith nonvalvular atrial fibrillation: SPORTIF ii: a dose-guiding, tolerability, and safety study

https://doi.org/10.1016/S0735-1097(03)00255-9Get rights and content
Under an Elsevier user license
open archive

Abstract

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.

Abbreviations

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)

Cited by (0)

Study funded by AstraZeneca Public Limited Company. Dr. Petersen served as a consultant to AstraZeneca.