Direct thrombin inhibitors versus vitamin K antagonists or LMWHs for prevention of venous thromboembolism following total hip or knee replacement

Direct thrombin inhibitors (ximelagatran, dabigatran and desirudin) may be as effective as LMWH and vitamin K antagonists in the prevention of major venous thromboembolism in total hip or knee replacement but seem to show higher mortality and cause more bleeding than LMWH.

A Cochrane review included 14 studies with a total of 21 642 subjects for efficacy and 27 360 for safety. Only patients subjected to elective total hip replacement (THR) or total knee replacement (TKR) were included but no patients with hip repair or hip fracture. Nine studies investigated ximelagatran, 4 oral dabigatran, and one subcutaneous desirudin. No difference was observed in major venous thromboembolism (VTE) in direct thrombin inhibitors (DTIs) compared with LMWH in total hip or knee replacement surgery (OR 0.91, 95% CI 0.69 to 1.19, statistical heterogeneity I² 71%; 11 studies, n= 17 428). Three studies compared DTIs versus warfarin (all used ximelagatran in TKR), and no difference was observed (OR 0.85, 95% CI 0.63 to 1.15; 3 studies, n= 4 327).

More total bleeding events were observed in the DTI group in patients subjected to THR (OR 1.40, 95% CI 1.06 to 1.85; I² 41%) compared with LMWH. No difference was observed between ximelagatran and warfarin in TKR (OR 1.76, 95% CI 0.91 to 3.38). All-cause mortality was higher in the DTI group compared with LMWH when the reported follow-up events were included (OR 2.06; 95% CI 1.10 to 3.87; 11 studies, n= 22 065). No severe hepatic complications were reported in the analysed studies. Studies that initiated anticoagulation before surgery showed less VTE events; those that began anticoagulation after surgery showed more VTE events in comparison with LMWH. Therefore, the effect of the DTIs compared with LMWH appears to be influenced by the time of initiation of coagulation more than the effect of the drug itself.

Comment: The quality of evidence is downgraded by inconsistency (variability in results across studies) and by potential reporting bias. Ximelagatran was removed from the market due to hepatocellular damage in February 2006.

Ədəbiyyat

1. Salazar CA, Malaga G, Malasquez G. Direct thrombin inhibitors versus vitamin K antagonists or low molecular weight heparins for prevention of venous thromboembolism following total hip or knee replacement. Cochrane Database Syst Rev 2010;(4):CD005981.