Low-molecular-weight heparin (nadroparin) and very low doses of warfarin in the prevention of upper extremity thrombosis in cancer patients with indwelling long-term central venous catheters: a pilot randomized trial.
OBJECTIVE
Upper extremity thrombosis is a major complication of central venous catheters implanted for chemotherapy in cancer patients. Vitamin K antagonists and low-molecular-weight heparins have been recommended in this setting, but their relative benefit-to-risk ratios have never been compared.


METHODS
A prospective, randomized, open, parallel-group, multicenter trial was performed comparing the antithrombotic efficacy and safety of warfarin and the low-molecular-weight heparin, nadroparin, in cancer patients who had undergone central venous catheter implantation. Warfarin was given orally at a fixed daily dose of 1 mg and nadroparin was injected subcutaneously at a fixed daily dose of 2,850 IU for 90 days, or until venographically-confirmed thrombosis occurred. The primary efficacy outcome was the occurrence of upper extremity thrombosis confirmed by venography performed 90 days after insertion of the catheter, or earlier if symptoms of thrombosis had appeared. Safety end-points were bleeding and thrombocytopenia.


RESULTS
Fifty-nine patients were included in the study. A total of 21 and 24 patients in the nadroparin and warfarin groups, respectively, were evaluable for primary efficacy. Six out of the 21 patients in the nadroparin group (28.6%) and 4 out of the 24 patients in the warfarin group (16.7%) had venographically-documented upper extremity thrombosis at day 90 (p=0.48). Safety was satisfactory and similar with both treatments.


CONCLUSIONS
Warfarin at a fixed, very low dose and nadroparin at a fixed, prophylactic dose had comparable benefit-to-risk ratios in the prevention of thrombosis associated with central venous catheters in cancer patients.
Mismetti
Patrick
P
Thrombosis Research Group Clinical Pharmacology Department, University Hospital Saint-Etienne, Clinique Mutualiste La Digonnière, France. patrick.mismetti@chu-st-etienne.fr
Mille
Dominique
D
Laporte
Silvy
S
Charlet
Véronique
V
Buchmüller-Cordier
Andréa
A
Jacquin
Jean-Philippe
JP
Fournel
Pierre
P
Dutrey-Dupagne
Claire
C
Decousus
Herv
H
D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage; D002405:Catheterization, Central Venous / Q000009:adverse effects*; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017762:Nadroparin / Q000008:administration & dosage; D009369:Neoplasms / Q000150:complications*; D010865:Pilot Projects; D011446:Prospective Studies; D013810:Therapeutic Equivalency; D013927:Thrombosis / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D016896:Treatment Outcome; D034941:Upper Extremity; D014859:Warfarin / Q000008:administration & dosage*
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D017762:Nadroparin; D014859:Warfarin