Astra Zeneca's new oral direct thrombin inhibitor, H 376/95, is reported to have shown greater efficacy than low molecular weight heparin as prophylaxis against venous thromboembolism in hip and knee replacement surgery.
This was shown in a study (known as METHRO II) which was presented at the recent International Congress on Thrombosis in Portugal.
H 376/95, which is still in clinical trials, is converted to the active form, melagatran, after absorption.
METHRO II included 1,916 patients, recruited in 13 European countries, including the UK, with two-thirds undergoing total hip replacement surgery and one-third having total knee replacement surgery. Patients were randomised to two regimens of thromboprophylaxis for eight to 11 days. One group received subcutaneous melagatran (1, 1.5, 2.25 or 3mg twice daily, or placebo), followed by oral H 376/95 (8, 12, 18 or 24mg twice daily). The other group received low molecular weight heparin (dalteparin 5000IU once daily subcutaneously, starting the evening before surgery). Thromboembolism was assessed on the final day of treatment and patients were followed up for four to six weeks post-operatively.
In hip replacement, venous thromboembolism occurred in 11.9 per cent of patients treated with the new thrombin inhibitor, compared with 25.5 per cent of patients treated with dalteparin (P<0.0001), with similar findings in knee replacement (22.0 per cent vs 33.7 per cent with dalteparin, P=0.0014).
Dr Bengt Eriksson (associate professor of orthopaedic surgery, Sahlgrenska University hospital, Gothenburg, Sweden), lead investigator of the study, commented: "H 376/95 has a number of practical advantages, especially oral administration, offering patients the possibility of taking tablets instead of having injections." Unlike warfarin, there was also no need for laboratory monitoring.
The study showed no difference in bleeding between H 376/95 and dalteparin.