Ximelagatran - Uses

Uses

Ximelagatran was expected to replace warfarin and sometimes aspirin and heparin in many therapeutic settings, including deep venous thrombosis, prevention of secondary venous thromboembolism and complications of atrial fibrillation such as stroke. The efficacy of ximelagatran for these indications had been well documented,, except for non valvular atrial fibrillation. The clinical efficacy of ximelagatran in preventing stroke and thrombo-embolic events in atrial fibrilation when compared with warfarin at INR 2–3 was evaluated in one open-label (SPORTIF-III) and one double-blind (SPORTIF-V) prospective randomized trial. The event rates in open label SPORTIF III were 1.64 vs. 2.30%, corresponding to a difference of − 0.66% (95% CI − 1.4, 0.13) and in double-blind SPORTIF V were 1.61 vs. 1.16%, corresponding to a difference of + 0.45% (95% CI = − 0.13, 1.03). These results were not considered to fulfil the current US FDA requirements to prove non-inferiority in efficacy. So ximelagatran was inferior to warfarin in this indication.These findings, in combination with evidence of liver toxicity and higher risk of coronary events, prevented the registration at the first application in the USA in 2004.

An advantage, according to early reports by its manufacturer, was that it could be taken orally without any monitoring of its anticoagulant properties. This would have set it apart from warfarin and heparin, which require monitoring of the international normalized ratio (INR) and the partial thromboplastin time (PTT), respectively. A disadvantage recognised early was the absence of an antidote in case acute bleeding develops, while warfarin can be antagonised by vitamin K and heparin by protamine sulfate.