The Pharmaceutical Journal
Vol 279 No 7474 433
20 October 2007

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Oral anticoagulant as effective as enoxaparin

Dabigatran etexilate, an oral anticoagulant, is as effective as enoxaparin in reducing the risk of venous thromboembolism after total hip replacement surgery, according to research published in The Lancet last month (2007;370:949).

Dabigatran etexilate is a prodrug that is rapidly converted to its active form dabigatran, which specifically and reversibly inhibits thrombin. It is administered orally and trials have shown that there is no need for coagulation monitoring.

The RENOVATE study, sponsored by the drug’s manufacturer Boehringer Ingelheim, was a phase III double-blind trial of 3,494 patients undergoing total hip replacement who were randomised to receive either dabigatran etexilate or enoxaparin.

Dabigatran etexilate was given at a dose of 220mg or 150mg orally, once daily, starting with a half dose one to four hours after surgery. Enoxaparin 40mg was given subcutaneously, once daily, starting the evening before surgery. The primary outcome was the composite of total venous thromboembolism (venographic or symptomatic) and death from all causes during treatment.

During a median treatment duration of 33 days, the researchers observed the primary outcome in 60 patients (6.7 per cent) in the enoxaparin group, in 53 patients (6.0 per cent) in the dabigatran 220mg group and in 75 patients (8.6 per cent) in the dabigatran 150mg group. Both doses of dabigatran were as effective as enoxaparin, say the researchers.

The researchers also found no significant difference in the frequency of major bleeding events between dabigatran 220mg and 150mg (2 per cent and 1.3 per cent, respectively) and enoxaparin (1.6 per cent). About half of all major bleeding events started before treatment. There were no major bleeding events reported after hospital discharge in the dabigatran groups.

“ On the basis of the ease of once-daily dosing and there being no need for coagulation monitoring, dabigatran etexilate can be considered to be an attractive alternative to other thromboprophylaxis regimens for patients undergoing total hip replacement surgery,” the researchers conclude.

The author of an accompanying editorial (ibid, p915) warns that, with major bleeding rates so low, tens of thousands of people would need to be randomised to provide definitive safety comparisons between dabigatran and enoxaparin.