ARIXTRA

1
ARIXTRA (fondaparinux sodium) in the
prevention of venous thromboembolism in major
orthopedic surgery.A Meta-Analysis of Four
Randomized Double-Blind Studies.
PENTAMAKS

• KA Bauer, BI Eriksson, MR Lassen, and AGG
  Turpieon behalf of the Steering Committees of
  the Pentasaccharide Orthopaedic Prophylaxis
  Studies

2
META-ANALYSIS OBJECTIVE AND DESIGN

• 4 multicenter, randomized, double-blind trials in
  7,344 patients comparing Arixtra o.d. with
  enoxaparin o.d. or b.i.d. in patients undergoing
  major orthopedic surgery.
• Total hip replacement surgery (THR) 2 trials,
• Major knee surgery (MKS) 1 trial,
• Hip fracture surgery (HFS) 1 trial.
• Same comparative drug, endpoints and Adjudication
  Committee.

3
META-ANALYSIS DESIGN
Treatment 7 2 Days
Arixtra 2.5 mg o.d.
start 6 2 hrs post-op
R
Enoxaparin 40 mg o.d. or 30 mg b.i.d.
start pre-op or post-op
Follow up Day 42 7
Venogram Day 511
4
META-ANALYSIS ENDPOINTS

• Primary efficacy VTE up to day 11
• deep-vein thrombosis (DVT) detected by mandatory
  bilateral venography, or
• documented symptomatic DVT, or
• pulmonary embolism.
• Primary safety Major bleeding.

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META-ANALYSIS EFFICACY RESULTS
Arixtra better
Enoxaparin better
Exact 95 CI
Hip replacement n 3,411
- 58.9 - 27.4
- 45.3
Hip fracture n 1,250
- 73.4 - 45.0
- 61.6
Knee replacement n 724
- 75.5 - 44.8
- 63.1
Overall odds reduction
- 63.1 - 45.8
p 10 -17
- 55.2
odds reduction
0
100
-100
-80
-60
-40
-20
20
40
60
80
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META-ANALYSIS SAFETY RESULTS
Arixtra N3,616 n () EnoxaparinN3,621n ()
Fatal bleeding 0 (0.0) 1 (0.0)
Bleeding in critical organ 0 (0.0) 1 (0.0)
Bleeding leading to reoperation 12 (0.3) 8 (0.2)
Bleeding with a bleeding index ? 2 84 (2.3) 53 (1.5)
The bleeding index was calculated as follows
number of units of packed red blood cells or
whole blood transfused (pre-bleeding) -
(post-bleeding) hemoglobin (g/dl) values.
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META-ANALYSIS CONCLUSION

• In patients undergoing major orthopedic surgery,
  Arixtra provided a significant benefit over
  enoxaparin in preventing DVT without increasing
  the risk of clinically relevant bleeding.