The Pharmaceutical Journal
Vol 269 No 7222 p636
2 November 2002

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Thrombin inhibitor more effective than enoxaparin at preventing blood clots

A novel direct thrombin inhibitor has been found to be more effective than enoxaparin (Clexane) at preventing venous thromboembolism in patients undergoing elective hip or knee replacement surgery.

The inhibitor is being developed by AstraZeneca as both a subcutaneous injection, melagatran, and in an oral formulation, ximelagatran, a prodrug of melagatran. Both will carry the brand name Exanta.

In the expanded prophylaxis evaluation surgery study (EXPRESS), researchers randomly assigned 2,764 patients undergoing surgery to receive either a regimen of melagatran 2mg immediately before surgery followed by melagatran 3mg in the evening after surgery and then ximelagatran 24mg twice daily (ximelagatran group) or enoxaparin 40mg daily started the evening before surgery. The total duration of treatment was eight to 11 days.

The researchers report that the regimen of melagatran and ximelagatran reduced the risk of proximal deep vein thrombosis (DVT) and pulmonary embolism by almost two thirds compared with that for enoxaparin — the rate of proximal DVT and pulmonary embolism was 2.3 per cent in the ximelagatran group (n=1,138) and 6.3 per cent in the enoxaparin group (n=1,178) (P<0.000002). The melagatran and ximelagatran regimen also reduced the risk of proximal and distal DVT, pulmonary embolism and total mortality by a quarter compared with that for enoxaparin — total rate of venous thromboembolism was 20.3 per cent in the ximelagatran group (n=1,141) and 26.6 per cent in the enoxaparin group (n=1,184) (P<0.0003).

The number of cases of symptomatic venous thromboembolism was eight in the ximelagatran group and 13 in the enoxaparin group. Bleeding events and transfusion rates were both more common in the ximelagatran group than in the enoxaparin group.

Ximelagatran in combination with melagatran is expected to receive a licence in the United Kingdom during the latter half of next year for the prevention of venous thromboembolism in patients undergoing knee and hip replacement surgery.

Data were presented at the International Congress on Thrombosis held in Bologna last week.