Primary and secondary prophylaxis of venous thromboembolism with low-molecular-weight heparins: prolonged thromboprophylaxis, an alternative to vitamin K antagonists

Abstract

Low-molecular-weight heparins (LMWHs) are used widely in the treatment and prevention of venous thromboembolism (VTE). The LMWHs dalteparin and enoxaparin reduce the rate of VTE by at least 50% if administered for 4-5 weeks following major orthopedic surgery, compared with in-hospital prophylaxis for 7-15 days. Meta-analyses have confirmed that the size of the reduction is similar for both clinical and asymptomatic VTE. Vitamin K antagonists (VKAs) have been shown to be associated with significantly higher bleeding rates compared with LMWH when used as prolonged prophylaxis against VTE following major orthopedic surgery. Patients with cancer are a recognized group at high risk of VTE, and those undergoing major surgery for their malignancy are at particular risk. Evidence from clinical trials is amassing to show that prolonged prophylaxis with LMWH (dalteparin, enoxaparin) in these patients can significantly reduce the rate of postoperative VTE. In cancer patients with acute VTE, the traditional approach is to initiate acute treatment with unfractionated heparin or LMWH followed by long-term treatment with VKA to prevent recurrence. However, clinical trial data have confirmed that the LMWH dalteparin, when administered for 6 months, is significantly more effective than VKA in preventing recurrence, cutting the rate of VTE by 52% without increasing the risk of bleeding. A new and intriguing area of interest is whether LMWH can enhance survival in patients with cancer. Preliminary data suggest that a biological effect of LMWH may act to prolong survival in patients with cancer.