GOTHENBURG, Sweden -- After hip replacement, an investigational oral thrombin inhibitor is an "attractive alternative" to prevent venous thrombosis, researchers here found.
GOTHENBURG, Sweden, Sept. 14 -- After hip replacement, an investigational oral thrombin inhibitor is an "attractive alternative" to prevent venous thrombosis, researchers here found.
In a randomized, double-blind study of nearly 3,500 patients, dabigatran etexilate (Rendix) was as good as subcutaneous enoxaparin (Lovenox) at preventing blood clots and death, according to Bengt Eriksson, M.D., of the Sahlgrenska University Hospital here, and international colleagues.
In the industry-sponsored study, the two drugs also had equivalent safety, Dr. Eriksson and colleagues reported in the Sept. 15 issue of The Lancet.
Treatment to prevent deep-vein clots is recommended after hip replacement surgery, because up to 20% of patients have thromboses, diagnosed by venography, despite routine prophylactic anti-coagulant therapy, Dr. Eriksson and colleagues said.
Such therapy is suggested for up to 11 days, but with hospital stays getting shorter, fewer patients get the full recommended treatment and often take aspirin instead. New oral treatments "are clearly needed," the researchers said.
The researchers compared two doses of dabigatran etexilate (220 and 150 mg daily) with 40 mg daily of exonaparin, with a combined endpoint of venous thrombosis (with or without symptoms) or death.
Patients were treated for a median of 33 days. Of the 3,494 patients, 1,157 got the high dose of dabigatran etexilate, 1,174 got the low dose, and 1,162 were treated with enoxaparin.
But because venography was either not available or was unreadable, 24% of the randomized patients were not included in the final efficacy analysis, leaving 880 patients in the high-dose dabigatran etexilate group, 874 in the low-dose group, and 897 in the enoxaparin group.
The researchers had defined a 7.7% difference in efficacy as the non-inferiority margin, determined by previous studies comparing enoxaparin with placebo.
The researchers found that:
The absolute differences in efficacy versus enoxaparin were 0.7% for the high dose of dabigatran etexilate and 1.9% for the low dose -- within the 7.7% non-inferiority margin.
The number of major bleeding events among patients on either dose of dabigatran etexilate was not significantly different than that seen among enoxaparin patients.
Liver enzyme elevations and acute coronary events were also not different, the researchers said.
The study is in "many important methodological respects exemplary," commented John Norrie, M.Sc., of the Centre for Healthcare Randomized Trials at Scotland's University of Aberdeen, in an accompanying editorial.
He noted that the loss of 24% of the patients creates a gap in the data, although the researchers -- on the basis of sensitivity analyses -- argued that the result is robust.
"The bottom line is that the effect of these missing data is unknown," he said.