The open-label study compared three intravenous doses of the monoclonal antibody abelacimab, given postoperatively, against a daily subcutaneous dose of enoxaparin.
A clot occurred in 22% of the enoxaparin recipients compared with 13% in the low dose group, 5% in the middle dose group and 4% with the highest dose (P<0.001 for the middle and highest doses).
Serious bleeding occurred in none of the 101 enoxaparin recipients and 2% or fewer among the 299 who received one of the three doses of abelacimab, which inhibits factor XI.
The findings also demonstrate that factor XI "is important for the development of postoperative venous thromboembolism," wrote the team, led by Dr. Jeffrey Weitz of McMaster University in Hamilton, Ontario.
The findings were also released virtually during the International Society on Thrombosis and Haemostasis' annual congress.
"The idea that a factor XI inhibition strategy can work just as well as -- or even better than -- enoxaparin is really paradigm-shifting in terms of our understanding of the pathogenesis of venous thrombosis," Dr. Weitz told Reuters Health in a telephone interview.
"Here we have a treatment that reduced the risk of postoperative venous thromboembolism by about 80% compared with enoxaparin but didn't increase the risk of bleeding," he said. "I think for sure doctors will be very heartened to see this."
The results come from volunteers treated at 16 centers in five countries.
Abelacimab was infused over 30 to 60 minutes 4 to 8 hours after surgery. Enoxaparin was given before or about 12 hours after surgery.
"All three abelacimab regimens met the criterion for noninferiority to enoxaparin," said the Weitz team. Superiority was seen in the two highest doses.
Nobody developed a symptomatic pulmonary embolism. The rates of serious adverse events were 3% among recipients of the middle dose of abelacimab and 1% among those getting the highest and lowest doses. Those events included two cases of medical device site joint infection, one wound infection and one case of coronavirus. There were no such instances among the enoxaparin recipients.
Among the 98 patients who received the highest dose of abelacimab, there were no cases of clinically relevant bleeding through day 30.
"The frequency of blood transfusions and postoperative hemoglobin levels with abelacimab were similar to those with enoxaparin," the researchers said.
Dr. Weitz, executive director of McMaster's Thrombosis and Atherosclerosis Research Institute, said he expects these results to reverberate well beyond these patients.
"Remember, bleeding is still the major complication and fear of bleeding is still a deterrent for patients who take anticoagulation treatment for atrial fibrillation," he said.
"Even when anticoagulants are prescribed, there's an inappropriate overuse of the lower dose regimens because doctors are afraid of bleeding. If we had safer anticoagulants, we could really revolutionize our management of patients with thrombotic disorders, and factor XI inhibitors are a promising class of agents for this group," Dr. Weitz said.
A phase 2 study of the drug in patients with atrial fibrillation is already underway.
The drug is also known as MAA868.
SOURCE: https://bit.ly/3rfeOwM The New England Journal of Medicine, online July 19, 2021.
By Gene Emery
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