Ximelagatran in Major Orthopedic Surgery: A Systematic Review and Meta-Analysis of Efficacy and Safety.
Authors: Lazo-Langner Alejandro , Rodger Marc A. , Wells Philip S. 
Published: April 2020

Abstract
Background. Venous thromboembolism (VTE) is a frequent complication of total hip (THR) and knee replacement (TKR). Current recommendations are to administer prophylaxis for at least 10 days with either low molecular weight heparin (LMWH), warfarin (warf) or fondaparinux. Ximelagatran (xim) might represent a convenient alternative not needing laboratory monitoring.
Methods. We conducted a protocolized systematic review of randomized control trials evaluating the use of xim (7&gt;d) for VTE prophylaxis in patients (pts) undergoing THR and TKR, screening MEDLINE, EMBASE, The Cochrane Library, and grey literature after 1980. Two reviewers assessed methodological quality using Jadad score and extracted data on outcomes (major VTE [proximal DVT, PE and death by PE], total VTE [assessed by venography], major bleeding and hepatic toxicity [ALT&gt;3x upper normal limit at venography]). Results were pooled using a random effects model. Subgroup and sensitivity analyses were done for type of surgery, xim dose, comparator, initial use of SC melagatran (mel) and methodological quality.
Results. Of 187 potentially relevant reports retrieved, 9 fulfilled the inclusion criteria. In total 13,756 pts were randomized to either xim (24&gt;mg bid x 7–12 d; 6,379 pts in 4 trials received initial SC mel) or a comparator (8,472 pts LMWH, 5,284 warf).
Pooled effect estimates of VTE and major bleeding in trials evaluating ximelagatran in orthopedic surgery Total Hip Replacement Total Knee Replacement OR(95% CI) p OR(95% CI) p NE Not evaluable. An OR &lt; 1 favours xim; an OR &gt; 1 favours comparator. All Studies Major VTE 0.76(0.29, 1.98) .58 0.68(0.53, 0.89) &lt;0.001 Total VTE 0.88(0.50, 1.55) 0.65 0.71(0.63, 0.80) &lt;0.001 Major Bleeding 1.70(0.78, 3.70) 0.18 1.38(0.86, 2.22) 0.19 Studies using SC melagatran Major VTE 1.49(1.20, 1.19) 0.12 0.53(0.33, 0.84) 0.008 Total VTE 0.70(0.36, 1.80) 0.31 0.77(0.61, 0.97) 0.03 Major Bleeding 2.05(0.81, 5.16) 0.13 1.12(0.55, 2.27) 0.76 Studies not using SC melagatran Major VTE NE NE 0.77(0.56, 1.06) 0.10 Total VTE NE NE 0.68(0.59, 0.78) &lt;0.001 Major Bleeding NE NE 1.63(0.86, 3.10) 0.13
In THR pts there were no differences in the odds of major or total VTE or major bleeding between the xim and LMWH groups. In TKR pts xim seemed to be superior to the comparator for preventing total VTE, however subgroup analysis showed that this might be true only for pts receiving initial SC mel or else, xim 36 mg. bid compared to warf (OR 0.64; 95%CI 0.55, 0.75; p&lt;0.001). In TKR pts xim was superior to LMWH for preventing major VTE only in the group receiving SC mel. Xim induced less cases of ALT elevation than LMWH and there were no differences when compared to warf
Pooled effect estimates of short-term liver toxicity in trials evaluating ximelagatran in orthopedic surgery OR(95% CI) p An OR &lt;1 favours xim; an OR &gt;1 favours comparator. Xim vs LMWH 0.36(0.25, 0.52) &lt;0.0001 Xim vs warf 0.81(0.30, 2.21) 0.69
Conclusion. Our results suggest that xim is not inferior to LMWH or warf for preventing VTE in patients undergoing THR or TKR and that in the latter it might even be superior to LMWH if initial SC mel is administered. Short-term liver toxicity seems to be less frequent in xim than in LMWH and no different from warf.