Bayer and Johnson & Johnson’s first-in-class oral blood thinner Xarelto is more efficacious and as safe as Sanofi-Aventis’ Lovenox in preventing venous thromboembolism (VTE) in patients undergoing knee replacement surgery.

This was the message that came from the RECORD3 study, the first Phase III results for Xarelto (rivaroxaban), the investigational oral direct Factor Xa inhibitor, presented at the XXI Congress of the International Society for Thrombosis and Haemostasis in Geneva, Switzerland. VTE manifests most commonly as deep vein thrombosis (DVT), usually in the leg, or pulmonary embolism (PE), a potentially life-threatening clot in the lungs. Patients undergoing major orthopaedic surgery such as knee replacement are at high risk of VTE, and Lovenox (enoxaparin) is currently recommended as the standard preventive treatment in these and other at-risk patients.

RECORD3 is the first trial to report from the RECORD programme, four studies investigating Xarelto in knee and hip replacement. Compared with Lovenox, Xarelto achieved a significant 49% relative risk reduction (RRR) in the composite primary endpoint of DVT, non-fatal PE and all-cause mortality. There was an even greater, also significant RRR of 62% in the risk of developing the secondary endpoint of major DVT (a composite of DVT in the thigh, non-fatal PE, and VTE-related death).

Importantly, this result for Xarelto was achieved with no increased risk of major bleeding compared to Lovenox or any signal of abnormal liver function tests. Bleeding is a risk with any anticoagulant, but liver tests have become a concern since the high-profile withdrawal last year of AstraZeneca’s Exanta (ximelagatran) due to liver safety concerns.

Speaking at a press conference on RECORD3, Professor Alexander Turpie, McMaster University, Canada commented: “Oral treatment with a Factor Xa inhibitor results in the most effective prophylaxis ever seen in patients undergoing major orthopaedic surgery. More than that, if this concept of Factor Xa works – and I think it will – it will revolutionise long-term oral anticoagulant therapy and it will completely change how we manage patients”.

Although major orthopaedic surgery is a large potential market for a new oral anticoagulant, the holy grail is to replace warfarin as long-term stroke prevention in the much larger group of patients with heart arrhythmias, an indication currently being tested for Xarelto in the Phase III ROCKET AF study. In the meantime, if results from the other RECORD studies match up to RECORD3, Bayer and J&J will be on track to submit Xarelto for VTE prevention in major orthopaedic surgery by the end of 2007 in Europe and during 2008 in the USA. This should put it ahead of Bristol Myers Squibb/Pfizer's apixaban, another direct Factor Xa inhibitor currently in Phase III. By Sue Lyon