Nadroparin 0.3 mL Versus Enoxaparin 40 mg in the Prevention of Venous Thromboembolism in Abdominal Surgery for Colorectal Cancer: A Randomized Double-Blind Comparative Study.
Authors: Simonneau Gerald 
Published: October 2019

Background: The relative benefit-to-risk ratio of various LMWH in the setting of colorectal cancer surgery has never been directly compared. Objective: We performed a multicenter, randomized, double-blind study to compare the efficacy and safety of enoxaparin 40 mg (4000 anti-Xa IU) and nadroparin 0.3 mL (2850 anti-Xa IU) in the prevention of venous thromboembolism (VTE) after colorectal cancer surgery.

Methods: Patients undergoing elective colorectal adenocarcinoma resection under general anesthesia were recruited. They were randomized to receive once daily either nadroparin 0.3 mL or enoxaparin 40 mg subcutaneously for 9±2 days, starting 2 to 4 hours preoperatively. The primary efficacy outcome was the composite of deep-vein thrombosis (DVT) detected by bilateral venography or documented symptomatic DVT or pulmonary embolism (PE) up to Day 12. The main safety outcomes were major bleeding and all-cause death. A blinded independent committee adjudicated all outcomes.

Results: A total of 1288 patients (median age: 69, range: 26–97 years; men: 61.4%) were randomized either to nadroparin (n=653) or to enoxaparin (n=635). Efficacy was evaluable in 950 (73.8%) patients who underwent contrast venography or had a symptomatic thromboembolic event. The rate of VTE at Day 12 was 15.9% for nadroparin and 12.6% for enoxaparin (relative risk reduction 21.3% [95% CI: −7.75; 42.5]). This difference was not statistically significant (p=0.13, Chi-squared test). In contrast, there were more symptomatic VTE, including symptomatic PE, in the enoxaparin group than in the nadroparin group (Table). Furthermore, the rate of major bleeding was significantly lower in nadroparin-treated patients than in enoxaparin-treated patients (Table). By Day 12, there were three (0.5%) deaths related to VTE or major bleeding in enoxaparin patients compared with none in nadroparin patients. By Day 60, 23 (3.5%) patients receiving nadroparin and 23 (3.5%) patients receiving enoxaparin had died.

Conclusion: Enoxaparin 40 mg was not more effective than nadroparin 0.3 mL in the prevention of total VTE in patients undergoing colorectal cancer surgery. The non-significant difference between the two groups was mainly due to a lower rate of asymptomatic distal DVT in the enoxaparin group than in the nadroparin group. However, nadroparin was more effective than enoxaparin for reducing symptomatic VTE, including PE, and was associated with significantly less major bleeding.

Efficacy and safety results at Day 12 Nadroparin 0.3 mL, n/N (%) Enoxaparin 40 mg, n/N (%) p *Chi-squared test Total VTE 74/464 (15.9) 61/486 (12.7) 0.13* Asymptomatic proximal DVT 15/503 (3.0) 14/515 (2.7) 0.81 Asymptomatic distal DVT 58/503 (11.5) 42/515 (8.2) 0.07 Symptomatic VTE 1/643 (0.2) 9/628 (1.4) 0.01 Symptomatic proximal DVT 1/643 (0.2) 4/628 (0.6) 0.22 Symptomatic PE 0/643 (0.0) 5/628 (0.8) 0.03 Major bleeding 47/643 (7.3) 72/628 (11.5) 0.01 All-cause death 2/643 (0.3) 8/628 (1.3) 0.06