New No-Needle Approach Prevents Blood Clots

Researchers from the University of Oklahoma (OU; USA), the University of Copenhagen (Denmark), and other institutions conducted a double-blind, double-dummy study involving 3,195 patients undergoing total knee replacement who underwent randomization. A total of 1,599 patients were assigned to receive 2.5 mg of apixaban orally twice daily, and 1,596 were assigned to receive enoxaparin injected subcutaneously every 12 hours; 908 subjects were not eligible for the efficacy analysis. Both medication groups were started 12 to 24 hours after surgery and continued for 10 to 14 days. The primary efficacy outcome was a composite of asymptomatic and symptomatic DVT, nonfatal pulmonary embolism, and death from any cause during treatment. Patients were followed for 60 days after anticoagulation therapy was stopped.

The researchers found that apixaban proved just as effective at preventing blood clots as enoxaparin, while reducing the risk of bleeding by half; the primary efficacy outcome was 9% with apixaban as compared with 8.8% with enoxaparin, and the composite incidence of major bleeding and clinically relevant nonmajor bleeding was 2.9% with apixaban and 4.3% with enoxaparin. The researchers concluded that despite the fact that apixaban did not meet the prespecified statistical criteria for noninferiority, its use was associated with lower rates of clinically relevant bleeding, and it had a similar adverse-event profile. A major point in favor of apixaban was that it is delivered orally. The study was published in the August 6, 2009, issue of the New England Journal of Medicine (NEJM).

"This is a major step in our fight to prevent DVT and the many unnecessary deaths each year caused by blood clots after joint replacement surgery. We now have a better treatment that reduces the risk of bleeding, and a patient no longer has to endure injections by needle,” said coauthor Gary Raskob, Ph.D., dean of the OU College of Public Health.

On average, 1-3% of people undergoing total joint replacement will end up with a symptomatic DVT or a pulmonary embolism. Apixaban--a specific factor Xa inhibitor currently in Phase III clinical trials--may provide effective thromboprophylaxis with a low risk of bleeding and improved ease of use compared to enoxaparin, a low-molecular-weight heparin that predominantly targets factor Xa but to some extent also inhibits thrombin.

Related Links:
University of Oklahoma
University of Copenhagen