PURPOSE: To examine the efficacy and safety of fondaparinux in Japanese patients with pulmonary embolism (PE) and/or deep vein thrombosis (DVT).
METHODS: We conducted two studies, one for acute PE and the other for acute DVT, in Japanese patients. Subjects were randomized to either the fondaparinux or unfractionated heparin (UFH) group in a 3:1 ratio. In the fondaparinux group, 5 mg (< 50 kg), 7.5 mg (50-100 kg), or 10 mg (>100 kg) was given once daily subcutaneously for 5 to 10 days as the initial treatment. In the UFH group, the reference group, the dose was adjusted to maintain activated partial thromboplastin time at 1.5 to 2.5 times the control value. Concomitant warfarin therapy was initiated following the start of initial treatment and continued alone until Day 90. The efficacy and safety were adjudicated blindly by the Central Independent Adjudication Committee.
RESULTS: Eighty patients were randomized to receive treatment in the two studies. In the pooled analysis, 57.9% were PE patients with DVT, and 45.9% were DVT patients with PE. No recurrent symptomatic venous thromboembolism (VTE), the primary efficacy endpoint, was noted. As assessed by multi-detector row computed tomography, the improvement rate at the end of the initial treatment and follow-up period was 71.4% and 86.8% in 42 patients with PE and 57.8% and 83.3% in 46 patients with DVT in the fondaparinux group, respectively. The rate of major bleeding during the initial treatment period, the primary safety endpoint, was 1.7% in the fondaparinux group. These results were comparable to those in the UFH group.
CONCLUSION: The efficacy of fondaparinux in reducing the risk of recurrent VTE was confirmed. Furthermore, tolerability was confirmed for the safety in Japanese patients.
CLINICAL IMPLICATIONS: PE and DVT are often complicated by each other. Fondaparinux, a factor Xa inhibitor, is a useful drug as initial treatment for acute PE or acute DVT patients, which allows simple once-daily subcutaneous administration without the need for monitoring of the coagulation system.
DISCLOSURE: Mashio Nakamura, Consultant fee, speaker bureau, advisory committee, etc. Mashio Nakamura, Yoshiaki Okano, Hiroki Minamiguchi, and Takeyoshi Kunieda received consultant fees from GSK-Japan.; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. These studies were sponsored by GSK-Japan.