The trial of 5,407 patients found that those given the pill apixaban were 64 percent less likely to develop clots in their legs or die than those given injections of Lovenox, the standard treatment. The research, dubbed Advance-3 and sponsored by Pfizer and Bristol-Myers, was published today in the New England Journal of Medicine. Both companies are based in New York.
A study released in March by the two drugmakers showed apixaban was superior to Lovenox in preventing clots from forming after knee-replacement surgery. Apixaban and similar new oral blood thinners will provide alternatives to difficult-to- use treatments such as warfarin, a 56-year-old anticoagulant -- first used as rat poison -- that requires constant monitoring, said the lead researcher, Michael Rud Lassen.
“This new drug offers a real advancement for patients,” said Lassen, a spine surgeon and a researcher with the University of Copenhagen’s department of orthopedics, in a telephone interview on Dec. 21. He said he will use apixaban in his patients if the drug is approved by regulators.
People undergoing hip or knee surgery are at risk of developing blood clots, and about 40 percent to 60 percent of patients getting the procedures develop clots if not treated preventively, Pfizer and Bristol-Myers said in a statement today. The global market for anticoagulants in 2009 rose to $690.5 million, from $686.2 million in 2008, and this year through September the market totaled $528.3 million, according to IMS Health Inc., a research company in Norwalk, Connecticut.
Pfizer and Bristol-Myers are asking for European approval for apixaban for use in patients undergoing hip and knee replacements. In the U.S., the companies are seeking marketing clearance of the drug for use in preventing strokes in patients with irregular heartbeat, or atrial fibrillation. The condition increases the likelihood of clots, said Jack Lawrence, the Bristol-Myers vice president in charge of apixaban development, in a telephone interview on Dec. 21.
Warfarin, the standard drug given to patients with atrial fibrillation, causes side effects and is difficult for doctors to dose and monitor to reduce bleeding risk. All blood-thinning medicines raise some risk of bleeding.
“There is great hope in the new oral anticoagulants and their potential to replace, to a large degree, the current standards of care,” Lawrence said. “Likely there will be room for multiple agents. Each drug will have subtle differences that might encourage one or the other to be prescribed.”
Blood Thinner Rivals
Johnson & Johnson, Bayer AG and Boehringer Ingelheim GmbH sell new oral medicines in Europe to prevent clots after hip and knee surgery.
Boehringer, based in Ingelheim, Germany, received U.S. approval in October for its anti-clotting drug Pradaxa to prevent stroke in patients who have atrial fibrillation, New Brunswick, New Jersey-based J&J and Leverkusen, Germany-based Bayer are awaiting U.S. clearance for their blood thinner Xarelto.
“The potential impact of these oral, highly specific, fixed-dose drugs that do not require routine monitoring will no doubt be substantial,” wrote Elaine Hylek, an associate professor of medicine at Boston University School of Medicine, in an editorial in the journal. If these drugs “prove to be effective across the broad spectrum of patients in routine care and are conscientiously priced, the worldwide impact will be huge.”
In the study, patients undergoing total hip replacement received either apixaban twice a day or an injection of Lovenox every 24 hours. Apixaban was started 12 to 24 hours after surgery, while Lovenox was begun 12 hours before surgery. Treatment continued for 35 days after surgery and patients were followed for an additional 60 days after completing their medicines.
The researchers found that 27 patients taking apixaban, or 1.4 percent, developed blood clots in the leg or a blockage in a lung artery or died. These figures compared with 74, or 3.9 percent, in the Lovenox group, giving those taking apixaban a 64 percent reduction in their risk of developing those complications, according to the report.
Those taking apixaban were also more than 50 percent less likely to develop blood clots in their upper legs, which can travel to the lungs, causing death, Lassen said. Bleeding occurred in a similar percentage of people taking either apixaban or Lovenox, the study showed.
In November, Bristol-Myers and Pfizer halted a trial of apixaban after an increase in bleeding outweighed benefits for patients who had recently suffered a heart attack or severe chest pain.
The companies are also studying apixaban as a treatment for blood clots in the legs and for pulmonary embolism, a condition in which the clot breaks free and travels to the lung, causing a blockage in a lung artery that can lead to death, Lawrence said.
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