A randomized study comparing the efficacy and safety of nadroparin 2850 IU (0.3 mL) vs. enoxaparin 4000 IU (40 mg) in the prevention of venous thromboembolism after colorectal surgery for cancer.
BACKGROUND
The optimal thromboprophylactic dosage regimen of low-molecular-weight heparins in high-risk general surgery remains debatable.


OBJECTIVE
We performed a randomized, double-blind study to compare the efficacy and safety of nadroparin 2850 IU (0.3 mL) and enoxaparin 4000 IU (40 mg) in the prevention of venous thromboembolism (VTE) after colorectal surgery for cancer.


METHODS
Patients undergoing resection of colorectal adenocarcinoma were randomized to receive once daily either 2850 IU nadroparin or 4000 IU enoxaparin s.c. for 9 +/- 2 days. The primary efficacy outcome was the composite of deep vein thrombosis (DVT) detected by bilateral venography or documented symptomatic DVT or pulmonary embolism up to day 12. The main safety outcome was major bleeding. A blinded independent committee adjudicated all outcomes.


RESULTS
Out of 1288 patients analyzed, efficacy was evaluable in 950 (73.8%) patients. The VTE rate was 15.9% (74/464) in nadroparin-treated patients and 12.6% (61/486) in enoxaparin-treated patients, a relative risk of 1.27 (95% confidence interval; CI: 0.93-1.74) that did not met the criterion for non-inferiority of nadroparin. The rate of proximal DVT was comparable in the two groups (3.2% vs. 2.9%, respectively), but that of symptomatic VTE was lower in nadroparin-treated patients (0.2% vs. 1.4%). There was significantly (P = 0.012) less major bleeding in nadroparin- than in enoxaparin-treated patients (7.3% vs. 11.5%, respectively).


CONCLUSIONS
Compared with those receiving enoxaparin 4000 IU, patients treated with nadroparin 2850 IU showed a higher incidence of asymptomatic distal DVT, but a lower incidence of symptomatic VTE. Nadroparin treatment was safer in terms of bleeding risk.
Simonneau
G
G
Department of Pulmonary and Critical Medicine, Antoine Beclere University Hospital, Clamart, France. gerald.simonneau@abc.aphp.fr
Laporte
S
S
Mismetti
P
P
Derlon
A
A
Samii
K
K
Samama
C-M
CM
Bergman
J-F
JF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000601:surgery*; D017984:Enoxaparin / Q000627:therapeutic use*; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017762:Nadroparin / Q000627:therapeutic use*; D011183:Postoperative Complications; D013923:Thromboembolism / Q000188:drug therapy / Q000517:prevention & control*; D020246:Venous Thrombosis / Q000188:drug therapy / Q000517:prevention & control*
D000925:Anticoagulants; D017984:Enoxaparin; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D017762:Nadroparin