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Supportive Oncology
Table 2: Efficacy and Safety of Nadroparin versus Enoxaparin in Colorectal Cancer Surgery
28
Nadroparin n/N(%) Enoxaparin n/N (%) Relative risk (95% CI)
Venous thromboembolism (primary outcome) 74/464 (15.9) 61/486 (12.6) 1.27 (0.93–1.74)
Any proximal deep-vein thrombosis 15/503 (3) 14/515 (2.7)
Distal deep-vein thrombosis only 58/503 (11.5) 42/515 (8.2)
Symptomatic venous thromboembolism 1/643 (0.2) 9/628 (1.4)
Symptomatic deep-vein thrombosis 1/643 (0.2) 5/628 (0.8)
Symptomatic pulmonary embolism 0/643 (0) 5/628 (0.8)
Major bleeding 47/643 (7.3) 72/628 (11.5) 0.64* (0.45–0.91)
Death from any cause 2/653 (0.3) 8/635 (1.3) 0.24** (0.05–1.15)
*p=0.012; **p=0.07.
Figure 1: Low-molecular-weight Heparins versus Unfractionated
true difference in efficacy between the various low-molecular-weight
Heparin in General Surgery (35 studies)
heparins and the nadroparin dosage regimen remains to be seen; however,
RR (95% CI)
in a meta-analysis of low-molecular-weight heparins in general surgery
Nadroparin (n=2,917; 5 studies) 0.61 (0.41–0.92)
patients, the sole low-molecular-weight heparin shown to be statistically
Certoparin (n=2,921; 11 studies) 0.86 (0.65–1.14)
more effective than unfractionated heparin was nadroparin (see Figure 1).
Daltaparin (n=2,764; 10 studies) 0.90 (0.65–1.26)
In this analysis, the safety of nadroparin in terms of bleeding risk was
Enoxaparin (n=4,919; 7 studies) 0.96 (0.77–1.19)
comparable to that of unfractionated heparin.
25
Parnaparin (n=173; 2 studies) 0.33 (0.05–2.08)
Relative risk 0 0.5 1 1.5 2
The efficacy and safety of a similar dosage regimen of nadroparin 2,850
LMWH better UFH better
anti-Xa IU once daily or 0.3ml were shown in cancer patients undergoing
Meta-analysis comparing the efficacy for preventing the occurrence of deep-vein thrombosis
other types of surgical procedures, as described below.
of various low-molecular-weight heparins (LMWH) with that of unfractionated heparin (UFH)
in patients undergoing general surgery.
25
Lung Surgery
compared with dalteparin 2,500 anti-Xa IU once daily in 194 patients The efficacy and safety of nadroparin in 150 patients undergoing lung
undergoing elective abdominal surgery; 92 patients had cancer (47.4%). surgery for cancer were investigated in a randomised, open trial.
36
The incidence of deep-vein thrombosis was 16.3% (95% CI 9–25) in the Nadroparin was given once daily either at a fixed dosage (2,850 anti-Xa IU
nadroparin group versus 32.3% (95% CI 23–43) in the dalteparin group. In or 0.3ml) or according to bodyweight (3,800 anti-Xa IU for those between
a subsequent study, the incidence of deep-vein thrombosis with once-daily 40 and 70kg, and 5,700 anti-Xa IU for those between 71 and 110kg).
5,000 IU dalteparin was 14.1% (95% CI 7–21).
31
Treatment was initiated 12 hours before surgery and continued for eight
days. No cases of symptomatic deep-vein thrombosis or pulmonary
Another randomised trial specifically examined the risk–benefit ratio embolism were reported in either study group. There were two major
of nadroparin in 61 patients undergoing major abdominal surgery for bleeding episodes in the fixed-dosage group, and six in the bodyweight-
cancer.
32
Nadroparin given at the same dosage regimen as in previous trials adjustment group.
significantly (p<0.01) reduced the incidence of deep-vein thrombosis from
35.4% without thromboprophylaxis to 6.8%. The volume of intra-operative Urological Surgery
blood loss or transfused blood and the number of patients with blood The efficacy and safety of nadroparin were compared with those of
transfusion or with wound haematomas were comparable in the two study unfractionated heparin in cancer patients undergoing radical retropubic
groups. However, a higher (p<0.05) post-operative transfusion requirement prostatectomy.
37
Fifty patients were randomly assigned to receive either
was observed in the group receiving nadroparin. once-daily 2,850 anti-Xa IU nadroparin (0.3ml) or thrice-daily 5,000U
unfractionated heparin. Nadroparin and unfractionated heparin were
These data all indicate that the same dosage regimen of nadroparin initiated 12 and two hours before surgery, respectively. Treatment was
(i.e. 2,850 anti-Xa IU once daily, or 0.3ml) is effective and safe in the maintained at least until hospital discharge. No patient in either group
prevention of venous thromboembolism after surgery, irrespective of presented symptomatic deep-vein thrombosis or pulmonary embolism.
whether patients have cancer. This is a noteworthy distinction between There was one major bleeding event in a patient treated with unfractionated
nadroparin and other low-molecular-weight heparins. In a subpopulation of heparin. During the first post-operative week, 42% of nadroparin and 57%
general surgery patients operated on for cancer, enoxaparin 20mg once of unfractionated heparin patients required transfusion.
daily (i.e. 2,000 anti-Xa IU) tended to be less effective than thrice-daily
5,000U unfractionated heparin.
33
A higher dose of enoxaparin (40mg once Neurosurgery
daily, or 4,000 anti-Xa IU) was required in order for this drug be as effective Craniotomy for brain neoplasm carries a high risk of venous
as unfractionated heparin; however, this result was obtained at the cost of thromboembolism.
38
Despite this, peri-operative anticoagulant prophylaxis
a trend towards an increased risk of major bleeding.
34
Likewise, in a for post-operative venous thromboembolism in neurosurgical patients has
subgroup of abdominal surgery patients with cancer, once-daily 5,000 anti- not gained wide acceptance because of the concern about intracranial
Xa IU dalteparin was more effective than once-daily 2,500 anti-Xa IU haemorrhage; physical methods are favoured by neurosurgeons. A
dalteparin for preventing venous thromboembolism (8.5 versus 14.9%; randomised, double-blind trial investigated the efficacy and safety of adding
p<0.05). The frequency of bleeding complications was not significantly nadroparin post-operatively to graduated compression stockings for the
different between the two arms (4.6 versus 3.6%).
35
Whether this reflects a prevention of venous thromboembolism in 485 patients, about 80% of
36 EUROPEAN ONCOLOGY
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