H.R. Buller, G. Agnelli

1
Treatment of Proximal Deep Vein Thrombosis
(DVT) Rivaroxaban Once or Twice Daily Had
Similar Efficacy and Safety to Standard Therapy
in Phase II Studies

• H.R. Buller, G. Agnelli
• Presented at the XXIst Congress of International
  Society on Thrombosis and Haemostasis (ISTH)
  2007 Meeting, July 6-12th in Geneva, Switzerland.

2
Treatment of Proximal DVT

• Background
• Rivaroxaban is an oral, direct Factor Xa
  inhibitor
• Objective
• To determine the safety and efficacy of
• Once or twice daily dosing of Rivaroxaban
• In patients with acute, systomatic, proximal DVT
  without pulmonary embolism (PE)
• Relative to standard therapy
• heparin/LMWHvitamin K antagonist INR 23

Buller, H.R. and G. Agnelli. Presented at ISTH
2007 in Geneva, Switzerland, abstract O-W-052.
3
Treatment of Proximal DVT

• Methods
• EINSTEIN-DVT (n543) Patients received
• Rivaroxaban 20 mg once daily (od)
• Rivaroxaban 30 mg od
• Rivaroxaban 40 mg od
• Or standard therapy
• Efficacy outcome
• Symptomatic, recurrent DVT or symptomatic PE
• recurrent venous thromboembolism VTE
• And asymptomatic deterioration on ultrasonography
  (US) or perfusion lung scan, at 3 months

Buller, H.R. and G. Agnelli. Presented at ISTH
2007 in Geneva, Switzerland, abstract O-W-052.
4
Treatment of Proximal DVT

• Methods
• ODIXa-DVT (n613) Patients received
• Rivaroxaban 10 mg twice daily (bid)
• Rivaroxaban 20 mg bid
• Rivaroxaban 30 mg bid
• Or standard therapy
• Efficacy outcome
• Thrombus regression on ultrasonography without
  recurrent VTE at 3 weeks
• Recurrent VTE and asymptomatic deterioration on
  ultrasonography at 3 months

Buller, H.R. and G. Agnelli. Presented at ISTH
2007 in Geneva, Switzerland, abstract O-W-052.
5
Study Designs
Enoxaparin(1 mg/kg)
Eligible patients those with symptomatic,
proximal DVT at baseline
Number of patients randomized CCUS complete
compression ultrasound PLS perfusion lung scan
CUS compression ultrasound
Buller, H.R. and G. Agnelli. Presented at ISTH
2007 in Geneva, Switzerland, abstract O-W-052.
6
Results
20 mg 30 mg 40 mg 60 mg Standard Therapy
ODIXa-DVT (bid study) ODIXa-DVT (bid study) ODIXa-DVT (bid study) ODIXa-DVT (bid study) ODIXa-DVT (bid study) ODIXa-DVT (bid study)
Efficacy outcome () 1.1 -- 1.1/3.0 1.0 1.0
Major bleeding () 1.7 -- 1.7/1.7 3.0 0
EINSTEIN-DVT (od study) EINSTEIN-DVT (od study) EINSTEIN-DVT (od study) EINSTEIN-DVT (od study) EINSTEIN-DVT (od study) EINSTEIN-DVT (od study)
Efficacy outcome () 6.1 5.4 6.6 -- 9.9
Major bleeding () 0.7 1.5 0 -- 1.5
Efficacy Outcome at 3 Months
Table Rivaroxaban (total daily dose)
Results are shown as 20 mg bid/40 mg bid.
20mg bid 40mg bid 60mg bid 40mg od Standard Therapy
Thrombus regression 53.0 59.2 43.8 45.9
Thrombus Regression at 3 Weeks
Buller, H.R. and G. Agnelli. Presented at ISTH
2007 in Geneva, Switzerland, abstract O-W-052.
7
Treatment of Proximal DVT

• Conclusion
• Rivaroxaban given either once or twice daily had
  similar efficacy and safety to standard therapy
• In patients with acute, systematic, proximal DVT
  without pulmonary embolism (PE)
• This oral direct factor Xa inhibitor can be given
  as the sole treatment in a fixed dose appears to
  be a very attractive alternative to standard
  therapy in patients with DVT

Buller, H.R. and G. Agnelli. Presented at ISTH
2007 in Geneva, Switzerland, abstract O-W-052.