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Editor's Correspondence
December 8/22, 2003

Fondaparinux and Prolonged Thromboprophylaxis After Hip Fracture Surgery—Reply

Arch Intern Med. 2003;163(22):2790. doi:10.1001/archinte.163.22.2789

In reply

My colleagues and I read with interest the comments of Dr Nurmohamed about the PENTHIFRA-Plus study.1 The importance of the duration of fondaparinux prophylaxis after major orthopedic surgery was first suggested in 4 previous short-term trials, since the efficacy of fondaparinux in preventing VTE was significantly related to the duration of its postoperative administration.2 Furthermore, in the 1-week PENTHIFRA trial in patients undergoing hip fracture surgery, 58.5% of fondaparinux-treated patients in whom a thromboembolic event did not occur received prolonged thromboprophylaxis with the investigators' choice of anticoagulant during follow-up.3 The PENTHIFRA-Plus study was the first trial to evaluate the benefit of extended thromboprophylaxis after hip fracture surgery. The incidence of VTE after 4-week fondaparinux therapy was therefore assumed on the basis of 2 previous long-term prophylaxis trials studying a low-molecular-weight heparin (LMWH) in a lower-risk group of patients undergoing elective hip replacement surgery.4,5 In the first of these trials,4 venography was systematically performed at discharge, and the VTE rate was 13% at the end of 1 week of treatment (31 DVTs in 238 patients). All these patients were excluded from the long-term trial. Four weeks after surgery, there were 6 additional VTEs in the group of patients randomized to long-term thromboprophylaxis with LMWH. If mandatory discharge venography would not have been performed, we can assume that half of the patients with asymptomatic DVT at discharge (ie, 15 patients) would have been enrolled in the group of 119 patients randomized to long-term thromboprophylaxis. Therefore, the total number of VTEs at the end of 4-week thromboprophylaxis would have been 21 (ie, an incidence of 17.6%). In the second long-term prophylaxis trial performed without mandatory discharge venography, the VTE rate at the end of 4-week treatment was also 18%.5 Thus, in patients undergoing total hip replacement surgery with LMWH therapy, the VTE rate increased from 13% at the end of 1-week treatment to 18% at the end of 4-week treatment (ie, a 1.4-fold increase).

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