Ximelagatran reduces post-MI events
The direct thrombin inhibitor ximelagatran (Exanta) reduces the risk of death, recurrent heart attack or severe chest pain by nearly one-quarter after six months' treatment on top of standard therapy, including aspirin. This finding comes from the first study of this new oral anticoagulant in patients who have had a myocardial infarction (MI).
The phase II study randomised 1,883 patients within 14 days of having
an MI to treatment with one of four doses of ximelagatran (24, 36, 48
or 60mg twice daily) or placebo. All patients were also treated with
aspirin and other agents, including statins and angiotensin-converting
enzyme (ACE) inhibitors, for the prevention of recurrent events.
Results at six months showed that ximelagatran reduced the risk of the
combined endpoint of death, recurrent non-fatal MI and severe, recurrent
chest pain from 16.3 per cent in the placebo group to 12.7 per cent,
corresponding to a relative risk reduction of 24 per cent (hazard ratio
0.76; 95 per cent confidence interval 0.59–0.98; P=0.036). The
lowest dose of ximelagatran achieved similar benefits to the higher doses,
so this
will be used in future post-MI trials.
Presenting the results at the recent European Society of Cardiology congress
in Vienna, Professor Lars Wallentin, Uppsala University Hospital, Sweden,
and lead investigator of the study, said: “The study supports the
concept that long-term treatment with an oral direct thrombin inhibitor
significantly reduces arterial thrombotic events.” He noted that
adding a platelet inhibitor with a different mode of action to aspirin
achieved additional benefits in reducing thromboembolism. Results showed
a 34 per cent reduction in the relative risk of death, MI and stroke
with ximelagatran.
Safety data from the ESTEEM study (efficacy and safety of the oral thrombin
inhibitor ximelagatran in combination with aspirin, in patients with
recent myocardial damage) showed that the risk of bleeding was relatively
low, with major bleeding events in 1.8 per cent of patients treated with
the drug compared with 0.9 per cent of those in the placebo group; 21.9
per cent of patients treated with ximelagatran suffered bleeds of any
kind (minor or major). Transient elevation of liver enzymes was greater
after two to three months’ treatment with ximelagatran than with
placebo, but this resolved in all patients whether or not they stopped
taking the drug. The study is published in The Lancet (2003;362:789). |
