Absence of transaminase increase after 4-week administration of fondaparinux (Arixtra^®), a new synthetic and selective inhibitor of factor Xa, in the PENTHIFRA-PLUS study

Abstract number: P2052

Lassen^* M., Bauer† K. A., Eriksson‡ B. I., Turpie§ A. G. G.

§Hamilton Health Sciences Corporation, Canada ‡Sahlgrenska University Hospital/ÖSTRA, Sweden; ^*University Hospital of Copenhagen Hillerød, Denmark; †VA Boston Healthcare System, USA;

Increases in serum transaminases are known adverse events of a number of antithrombotic compounds. Fondaparinux is a new synthetic selective inhibitor of factor Xa. In four studies involving 7344 patients undergoing major orthopedic surgery, a once-daily subcutaneous dose of 2.5 mg fondaparinux starting 6 h postoperatively, reduced the incidence of venous thromboembolism (VTE) by 55.2%, as compared with enoxaparin, without significantly increasing the risk of clinically important bleeding. No significant increase in transaminases clearly related to fondaparinux was identified up to day 11. However, in trials with peri-operative measurement of transaminases and using an active control, it is difficult to sort out whether the variations of serum transaminases observed are related to the surgical context or induced by study drugs. In the PENTHIFRA-PLUS study, hip fracture surgery patients were exposed to fondaparinux up to 4 weeks postoperatively, and the efficacy and safety of fondaparinux was compared in a randomized and double-blind manner to placebo. After an initial open-label treatment of once-daily 2.5 mg of fondaparinux for 7 ± 1 days, 656 patients were randomized to receive either the same dose-regimen of fondaparinux or placebo for 21 ± 2 days. The incidence of all VTE and symptomatic VTE was reduced to a very low absolute incidence of 1.4% and 0.3%, compared with 35.0% and 2.7% with placebo (relative risk reductions: 95.9% and 88.8%, P < 0.001 and P = 0.021). Serum transaminases were measured at randomization and at the end of the study. The results show that transaminase increase was rare both in the fondaparinux and placebo groups and variations in transaminases were comparable between the two groups (Table 1). Thus, prolonged administration of 2.5 mg fondaparinux for up to 4 weeks was no more likely to induce significant changes in liver enzymes than placebo.

Table 1.  Variations in transaminases between randomization and the end of the study