Clinical Experience of Nadroparin in Patients with Cancer

Clinical Experience of Nadroparin in Patients with Cancer

Franco Piovella, Marisa Barone


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Short-term Initial Treatment
Venous thromboembolism appears to be more aggressive in cancer patients. Compared with non-cancer patients, deep-vein thrombosis is more frequently bilateral, located in the more proximal veins or at unusual sites.8,55,56 Furthermore, antithrombotic drugs are less effective and their use associated with more bleeding complications. Compared with patients without cancer, cancer patients have a two- to three-fold higher risk of recurrent thrombosis and a two- to six-fold higher risk of haemorrhagic complications.57–59 Despite this, international guidelines on the initial treatment of venous thromboembolism in patients with cancer are not specific to this population.2–4 A recent meta-analysis of clinical trials performed in the general population with venous thromboembolism showed that the risk–benefit ratio of low-molecular-weight heparins was better than that of unfractionated heparin, with a greater efficacy for reducing recurrence and overall death.60 This greater efficacy of lowmolecular-weight heparins was also confirmed in a group of patients with cancer.61 In patients with pulmonary embolism, low-molecular-weight heparins were at least as effective and safe as unfractionated heparin.62 As their use is also easier from a practical perspective, low-molecular-weight heparins are generally preferred for the initial five- to 10-day treatment of venous thromboembolism, including in patients with cancer.2–4

As for other low-molecular-weight heparins, no trial has specifically studied nadroparin in the initial treatment of venous thromboembolism in patients with cancer. In the nadroparin trials in this setting,63–65 cancer patients represented a subgroup, varying between 14 and 22% (see Table 3). Overall, these trials showed that nadroparin administered once or twice daily was both efficacious and safe in terms of bleeding risk in the initial treatment of patients with venous thromboembolism. The once-daily regimen of nadroparin at double concentration is particularly attractive for patients with cancer who are already receiving a number of other drugs. Of note, the efficacy of such a once-daily regimen has not been demonstrated for all of the other available low-molecular-weight heparins.66,67

Several reports have shown that the outpatient treatment of venous thromboembolism in cancer patients was safe and effective,68,69 a particularly interesting result in this population, who are frequently hospitalised for many other reasons. The benefit of nadroparin in the outpatient treatment of patients with venous thromboembolism has also been proved in several trials, which included 13–18% cancer patients.70,71

Long-term Secondary Prevention
The use of vitamin K antagonists is particularly problematic in patients with cancer, with a significantly greater risk of unpredictable levels of anticoagulation due to frequent drug interactions, malnutrition, vomiting or liver dysfunction. Their use also requires frequent laboratory monitoring.72 Low-molecular-weight heparins do not have these drawbacks.73 Furthermore, in the long-term secondary prevention of venous thromboembolism in patients with cancer, low-molecular-weight heparins were shown to be at least as effective and safe as vitamin K antagonists.74,75 These drugs also improved the quality of life of palliative care cancer patients, who felt liberated from hospitals or clinics.76 Thus, in international guidelines on the long-term treatment of venous thromboembolism in patients with cancer,2–4 low-molecular-weight heparins are recommended for the first three to six months after the event; the consideration of anticoagulation for an indefinite period for patients with active cancer (metastatic disease or continuing chemotherapy) is also proposed.

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