New drug prevents dangerous complications of hip and knee surgery

A McMaster University researcher predicts a new oral blood thinner will revolutionize treatment for preventing dangerous blood clots in patients undergoing hip and knee surgery.

Dr. Alexander Turpie, professor of medicine at the Michael G. DeGroote School of Medicine, oversaw four major international studies on the drug rivaroxaban (Xarelto).

All studies found the drug was significantly more effective than the current standard enoxaparin (low molecular weight heparin) in preventing venous thrombosis (VTE). VTE begins with a blood clot in a vein and is a serious, frequent and potentially fatal complication of major orthopedic surgery.

Heparin and warfarin are the anticoagulants commonly used to treat this condition, but warfarin, in particular, is difficult to monitor because it changes with diet, other drugs and alcohol.

“Much of that will be overcome with this new drug,” Turpie said.

Turpie chairs the executive committee for the RECORD clinical program (Regulation of Coagulation in major Orthopedic surgery reducing the Risk of DVT and PE), a global program of four clinical trials (RECORDS1, 2, 3 and 4) involving more than 12,500 patients which is comparing oral rivaroxaban with injectable enoxaparin.

He is presenting a meta-analysis of the four studies on Thursday, June 26 at the 20th International Congress on Thrombosis in Athens, Greece.

“It will be the first time people will see the dramatic benefits,” he said. “When you put it all together, you can see the growth and potential for this drug.”

Results of the RECORD3 clinical trial, of which Turpie is the senior author, appear today in the New England Journal of Medicine (NEJM).

RECORD3 is a randomized, double-blind trial of 2,531 patients undergoing total knee replacement surgery. Patients received either oral rivaroxaban, 10 mg once daily, beginning six to eight hours after surgery, or a 40 mg injection of enoxaparin once a day, beginning 12 hours before surgery. Both treatments continued for 10 to 14 days.

For patients treated with rivaroxaban, there was a 49 per cent relative risk reduction (RRR) in total VTE and a 62 per cent RRR in major VTE compared with those treated with enoxaparin. Both drugs showed a low rate of bleeding.

In the same NEJM issues, other researchers reported on the RECORD1 study, which also found that rivaroxaban was “significantly more effective” than enoxaparin.

An accompanying editorial in the NEJM suggested the positive reports from the two RECORD studies raises questions that reach far beyond individual drugs to the overall process of drug development, such as what are the guiding principles for developing safe, effective and widely applicable anticoagulants?

Rivaroxaban is a novel, oral, once-daily direct Factor Xa inhibitor in advanced clinical development for a wide range of indications to prevent and treat blood clots. It works at a pivotal stage in the complex coagulation process to directly inhibit the enzyme Factor Xa. Based on extensive studies, the drug has been shown to have a wide therapeutic window without the need for routine monitoring.

The drug is being jointly developed by Bayer HealthCare and Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

It is not licensed for sale in Canada. Bayer Inc. has submitted a regulatory filing to Health Canada for approval to market rivaroxaban.

The number of total knee and total hip replacements is rising in Canada, with the majority of procedures being performed on people aged 55 and older.

From 2004 to 2005, close to 60,000 people underwent hip and knee replacement surgeries in Canada. Among these patients, blood clots are the most common cause of re-hospitalization. VTE is considered the most frequent preventable serious and potentially fatal complication following major orthopedic surgery.

The threat of blood clots goes far beyond orthopedic surgeries: Blood clots are one of the leading causes of global disease and death in many patients, including those with atrial fibrillation, heart attack and acutely ill hospitalized patients, such as those with cancer.