Current prophylactic regimens against deep-vein thrombosis (DVT) following hip surgery include subcutaneous low-molecular-weight heparin (LMWH) initiated on a delayed basis or oral anticoagulants. Recent clinical trials suggest that LMWH initiated in closer proximity to surgery, which harmonizes with the perioperative initiation of DVT, is more effective than current clinical practice. LMWH initiated 4-6 hours after surgery (just-in-time regimen) has shown superior efficacy vs oral anticoagulants. LMWH initiated 12 hours before surgery or 12-24 hours postoperatively was not more effective than oral anticoagulants. We performed a systematic review of the literature to assess the efficacy and safety of the direct thrombin inhibitor melagatran or ximelagatran and the pentasaccharide fondaparinux administered at different times in relation to surgery vs LMWH or oral anticoagulants.
Studies were identified using MEDLINE, reviewing references from retrieved articles and scanning abstracts from conference proceedings. Randomized trials comparing direct thrombin inhibitors or pentasaccharides administered at different times relative to surgery vs LMWH or oral anticoagulants for prophylaxis in hip or knee surgery patients evaluated using contrast venography were selected. Two reviewers extracted data independently.
Subcutaneous melagatran given immediately prior to surgery followed by oral ximelagatran has shown superior efficacy when compared with LMWH started the evening before surgery (p<0.0001). With prophylaxis initiated the morning after surgery, ximelagatran was statistically significantly less effective than LMWH. Three additional studies evaluating melagatran/ximelagatran versus LMWH or oral anticoagulant prophylaxis confirm the importance of timing. When compared with LMWH initiated 12 hours preoperatively, fondaparinux started 6 hours postoperatively revealed significantly lower incidences of DVT (p<0.0001).CONCLUSIONS: In comparing new regimens for thromboprophylaxis against classical regimens, initiation time of each regimen is a critical factor. For the melagatran-ximelagatran regimen, timing dominated the effect of the regimen as administered.
Lower DVT rates are seen when antithrombotic agents are initiated in close proximity to surgery.
R.D. Hull, None.