Last update:
23-Jul-2008

Arch Hellen Med, 2000, 17(Supplement):64-70

LECTURE

Thromboprophylaxis:
Focus on high-risk orthopedic surgery
and the novel oral direct thrombin inhibitor H 376/95 and its active form melagatran

O.E. DAHL
Senior Researcher, Chief Surgeon, Department of Orthopaedics Research Forum,
Ullevaal University Hospital Oslo, Norway

Following major orthopedic surgery, such as total hip or total knee replacement (THR, TKR), thromboprophylaxis against venous thromboembolism (VTE) is usually continued for 7–10 days. However, in the 2–3 month period after THR there is reduced patient survival compared with the general population, with the majority of mortalities due to cardiorespiratory and vascular complications, including VTE. In addition, several studies have shown that symptoms of deep vein thrombosis occurred on average 27 (range 3–150) days after THR, and these data parallel an increase in subclinical VTE found after hospital discharge. It therefore seems that an extended period of thromboprophylaxis may be beneficial. Extended thromboprophylaxis for up to 35 days with low molecular weight heparin has been shown to significantly reduce the incidence of VTE. However, the use of current anticoagulants is limited and there is a need for a flexible prophylaxis for both inpatient and outpatient administration, which can be given parenterally and orally, without the need for coagulation monitoring. H 376/95 is a novel, oral, direct thrombin inhibitor that represents a new therapeutic concept in oral anticoagulant treatment. Pharmacokinetic studies in healthy volunteers have shown that melagatran, the active form of H 376/95, has a highly predictable and stable pharmacokinetic profile, with no clinically significant food or drug interactions. In a clinical study (METHRO II) in 1876 patients, sequential therapy with subcutaneous melagatran followed by oral H 376/95 was given for prophylaxis of VTE after THR or TKR. The results showed that melagatran followed by H 376/95 was efficacious and well tolerated. In conclusion, H 376/95 seems, to offer significant improvement in the medical management of thrombosis and may offer convenient long-term patient use without the need for routine coagulation monitoring.

Key words: Direct thrombin inhibitor, H 376/95, Major orthopedic surgery, Melagatran, Thromboprophylaxis.