Ximelagatran continues to show promise as anticoagulation agent
Promising results from two clinical trials of a new anticoagulant were published last month in The New England Journal of Medicine.
Ximelagatran (Exanta), manufactured by AstraZeneca, is an orally administered
direct thrombin inhibitor. Researchers say that the agent does not require
monitoring of coagulation or dose adjustment.
Ximelagatran was compared with warfarin for the prevention of venous
thromboembolism after total knee replacement in a multicentre study of
1,851 patients. At a dose of 36mg twice daily, the new agent was superior
to warfarin for the composite end point of venous thromboembolism and
death from all causes (20.3 per cent versus 27.6 per cent). There were
no significant differences in the incidence of major bleeding or the
composite secondary end point of proximal deep vein thrombosis, pulmonary
embolism and death (2003;349:1703). A previous trial had found that a
dose of 24mg ximelagatran had a similar efficacy to warfarin.
A report from the same journal showed that the new anticoagulant was
superior to placebo for secondary prevention of venous thromboembolism.
In a double blind, multicentre trial, 1,233 patients with venous thromboembolism
who had undergone six months of anticoagulant therapy were assigned extended
secondary prevention with either ximelagatran 24mg daily or placebo for
18 months without coagulation monitoring.
A recurrence of venous thromboembolism was seen in 12 out of 612 patients
treated with the active agent and 71 out of 611 given placebo. There
was no significant increase in bleeding complications with the active
drug, although there was an increase in the number of patients with transient
elevation in alanine aminotransferase levels.
The authors say that, for many patients with venous thromboembolism,
secondary prevention with vitamin K antagonists is not extended beyond
six months because the risk of recurrence may be outweighed by the risk
of major bleeding.
The author of an accompanying editorial welcomed the studies but warned
that liver function abnormalities seen in patients treated with ximelagatran,
although mostly transient, are of some concern (ibid, p1762). |
