Fondaparinux Requires Further Study Before Firm Recommendation

British orthopedic surgeons are a skeptical group, and when it comes to chemoprophylaxis for venous thromboembolism, strong opinions are guaranteed to emerge, especially in the light of a new anticoagulant. The editorial by Heit¹ clearly highlights the clinical and economic arguments for thromboprophylaxis and succinctly outlines the potential benefits and shortcomings of fondaparinux compared with low-molecular-weight heparin.¹ Fondaparinux offers a benefit with an overall 50% reduction in venographic deep vein thrombosis, but without reduction in symptomatic end points at day 11 or in fatal and nonfatal pulmonary embolism and mortality at day 49.² Even if the venographic reductions translated into fractional reductions in clinical end points, such a marginal reduction must be balanced against an absolute 1% increase in bleeding.^1,3 Safety is the central concern of surgeons in the United Kingdom, not marginal increases in efficacy. One of the fondaparinux studies investigated hip fracture and highlighted the need for improved thromboprophylaxis strategy in these patients (fatal thromboembolic events occurred in 1% at day 49).⁴ As with most clinical trials, the patients with hip fracture were highly selected; those with impaired renal function or any hemorrhagic tendency were excluded. Although the need for improved prophylaxis is clear, elderly, fragile patients with hip fracture must be carefully screened before exposure to fondaparinux, especially given its long half-life and lack of antidote. Given the price premium for fondaparinux (more than 50% in the United Kingdom), I concur with Heit¹ that detailed cost-effectiveness analyses, both from a US and a UK perspective, are required before this novel synthetic indirect factor Xa inhibitor can be firmly recommended.