Extended prophylaxis of venous thromboembolism with idraparinux.
BACKGROUND
The extended use of vitamin K antagonists for prophylaxis against venous thromboembolism is often constrained by risk-benefit limitations and inconvenience. We evaluated the efficacy and safety of a 6-month extension of prophylaxis against recurrent venous thromboembolism with idraparinux in patients who had initially received 6 months of prophylaxis with an anticoagulant.


METHODS
We randomly assigned patients who had completed 6 months of prophylaxis with idraparinux or a vitamin K antagonist and in whom extended anticoagulation was warranted to receive once-weekly injections of 2.5 mg of idraparinux or placebo for 6 months without monitoring. The primary efficacy and safety outcomes were recurrent venous thromboembolism and major bleeding.


RESULTS
Of 1215 patients, 6 of 594 (1.0%) in the idraparinux group and 23 of 621 (3.7%) in the placebo group had recurrent venous thromboembolism (P=0.002). Major bleeding occurred in 11 patients (1.9%) in the idraparinux group and in none in the placebo group (P<0.001). Of these 11 episodes, 3 were fatal intracranial hemorrhages. As compared with patients whose initial treatment was a vitamin K antagonist, patients whose initial treatment was idraparinux who were assigned to 6 months in the placebo group had a lower incidence of recurrent thromboembolism (0.7% vs. 5.9%); patients who received 6 additional months of idraparinux therapy had a higher incidence of major bleeding (3.1% vs. 0.9%).


CONCLUSIONS
During a 6-month extension of thromboprophylaxis, idraparinux was effective in preventing recurrent thromboembolism but was associated with an increased risk of a major hemorrhage. (ClinicalTrials.gov number, NCT00071279 [ClinicalTrials.gov].).
Academic Medical Center, Department of Vascular Medicine, F4-211, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. h.r.buller@amc.uva.nl
Buller
Harry R
HR
Cohen
Ander T
AT
Davidson
Bruce
B
Decousus
Hervé
H
Gallus
Alex S
AS
Gent
Michael
M
Pillion
Gerard
G
Piovella
Franco
F
Prins
Martin H
MH
Raskob
Gary E
GE
D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D065427:Factor Xa Inhibitors; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007279:Injections, Subcutaneous; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009844:Oligosaccharides / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D011655:Pulmonary Embolism / Q000188:drug therapy* / Q000401:mortality; D055502:Secondary Prevention; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000188:drug therapy* / Q000401:mortality; D014812:Vitamin K / Q000037:antagonists & inhibitors
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009844:Oligosaccharides; D014812:Vitamin K; C479958:idraparinux