Orlando, FL - The investigational oral anticoagulant dabigatran looks to be as effective as the current standard of care, the low-molecular-weight heparin enoxaparin, in the prevention of venous thromboembolism (VTE) after orthopedic surgery, but has "a clear benefit" in offering oral administration in place of subcutaneous injection [1]. So says Dr Bengt Eriksson (University Hospital Sahlgrenska/Östra, Gothenburg, Sweden), speaking at the American Society of Hematology 48th Annual Meeting. He was presenting results from the RE-MODEL study in 2076 patients.

Once the drug is available (the launch is expected in 2008), Eriksson predicts that there will be a gradual shift away from the use of enoxaparin to dabigatran, in both the United States and Europe. "The benefit is convenience, while safety and efficacy are at the same level," he said in an interview.

An oral drug is far more convenient for patients, he commented. These orthopedic patients are discharged from the hospital four days after surgery, but they need to continue taking the drug for a further 10 to 14 days, he explained, and it is much easier for them to swallow a pill than to inject subcutaneously. Another advantage is that dabigatran is given at a fixed dose and does not need to be adjusted for age or weight. It also appears to be free of drug-drug and drug-food interactions, he said.

In this trial, there was no signal of liver toxicity, he commented, although he added that the drug was used short term, for just longer than a week, and so "we cannot draw any definite conclusions." He pointed out that the liver problems with a predecessor, ximelagatran, were seen after several weeks on the drug, in patients who had been taking it for five to eight weeks, so "we still need to wait for longer-term data on this drug, and this should come from the ongoing studies."

The study that Eriksson was presenting is one of several phase 3 studies sponsored by the manufacturer of dabigatran, Boehringer Ingelheim. Two others are still ongoing—RE-NOVATE, in hip-replacement patients, is also looking at VTE prevention, while RE-LY involves patients with atrial fibrillation taking the drug to prevent stroke.

RE-MODEL was designed as a noninferiority trial, and this was shown by dabigatran at both doses tested. Dabigatran was administered at 150 mg or 220 mg once daily, with a half dose given on day of surgery one to four hours postoperatively, while enoxaparin 40 mg was given once daily by subcutaneous injection and was started 12 hours before surgery. Treatment was continued for 6 to 10 days, with follow-up at three months after surgery.

All three groups had similar results for the primary end point of total VTE and all-cause mortality and for the secondary end point of proximal deep vein thrombosis (DVT) and/or pulmonary embolism (PE) (collectively termed VTE). One patient died in each group. Side effects were also similar across the three arms, including the results for elevated liver-function tests (LFT); elevated liver function was defined as alanine transaminase (ALT) levels more than three times the upper limit of normal.

"Although considerable progress has been made in the treatment of VTE, new advances are emerging that have the potential to rapidly change the therapeutic scenario," Eriksson said in a statement. "The analysis of these phase 3 data confirms that once-daily dabigatran etexilate, given early in the postoperative period, was as safe and effective as the standard of care in preventing VTE for patients undergoing total knee replacement."