Perspective:

This important meta-analysis provides additional perspective on the relative benefits of factor Xa inhibitors versus LMWH for VTE prophylaxis after knee or hip replacement surgery. This is an important topic because the incidence of VTE after such surgery is historically high. The topic will remain controversial, however. The authors themselves point out that the very small number of events observed suggest that if there is any difference between these agents, it is quite small. Furthermore, the bleeding outcomes were often treated as a composite event, most often only ‘major bleeding,’ which may grossly undercount wound hematoma, or minor wound bleeding. This is a concern for the operating surgeons, as it may predispose to wound infections. Also, mandatory venographic screening was performed at the end of prophylaxis in all trials. This may have overcounted endpoints with the discovery of clinically silent DVT. (On the other hand, this may have resulted in the discovery of clinically minor DVTs which, because of treatment, never became symptomatic, resulting in an undercount of symptomatic DVT events.)

The most recent edition of the American College of Chest Physicians antithrombotic guidelines reflects the confusion in this field by recommending no fewer than 8 agents (including aspirin alone), as supportable by the literature for VTE prophylaxis in this situation. Given the cost of comparative effectiveness studies, and the conflicting concerns of interested parties, the controversy over best prophylaxis is unlikely to be resolved soon.