Is Low-Molecular-Weight Heparin Safer Than Warfarin for Secondary Prevention of Venous Thromboembolism in Cancer Patients?—Reply

In reply

We thank Dr Theerman for his comments on the INR target in patients receiving oral anticoagulants. Although we agree that this treatment was associated with a high rate of bleeding in our patients, we do not agree with his suggestion of maintaining patients with acute VTE on a lower level of oral anticoagulation. Our study was designed to test a novel anticoagulant strategy (ie, long-term LMWH therapy), which has to be compared with a reference regimen. Warfarin therapy adjusted to obtain an INR of 2 to 3 is the current recommendation for treating VTE and is supported by a large body of literature.¹ In addition, strong and consistent data support that low INR values are associated with a high risk of recurrent thrombosis.² Finally, although patients with cancer are known to have an increased risk of bleeding when receiving anticoagulants, they also carry a higher risk of thromboembolic recurrences.³ In our study, the recurrence rate in the warfarin group was twice higher than in the LMWH group, and a lower-intensity warfarin therapy may have resulted in an even higher rate of thromboembolic complications in this group.⁴ As suggested by Dr Theerman, most of the major bleeding episodes were observed at the time the INR value was greater than 3. The question is not the level of desired anticoagulation but the difficulty in maintaining the INR at a prespecified level, which appears more difficult in patients with cancer than in those without.