Rivaroxaban: An Oral, Direct Factor Xa Inhibitor for the Prevention of Venous Thromboembolism in Total Knee Replacement Surgery

1
Rivaroxaban An Oral, Direct Factor Xa Inhibitor
for the Prevention of Venous Thromboembolism in
Total Knee Replacement Surgery Results of the
RECORD 3 Study

• M.R. Lassen, A.G. Turpie, N. Rosencher,
  L.C. Borris, W. Ageno, J.R. Lieberman,
  T.J. Bandel, F. Misselwitz
• Presented at the XXIst Congress of International
  Society on Thrombosis and Haemostasis (ISTH)
  2007 Meeting, July 6-12th in Geneva, Switzerland.

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Rivaroxaban An Oral, Direct Factor Xa Inhibitor
for the Prevention of VTE in Total Knee
Replacement Surgery Results of the RECORD 3
Study
Background

• Rivaroxaban is a novel, oral, direct Factor Xa
  inhibitor

Objective

• To determine the efficacy and safety of
  once-daily (qd) rivaroxaban as compared to qd
  enoxaparin for the prevention of venous
  thromboembolism (VTE) in patients undergoing
  total knee arthroplasty (TKA)

Lassen MR, et al. Presented at ISTH 2007 in
Geneva, Switzerland, abstract O-S-006-B.
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Rivaroxaban An Oral, Direct Factor Xa Inhibitor
for the Prevention of VTE in Total Knee
Replacement Surgery Results of the RECORD 3
Study
Methods

• Double-blind trial
• Randomized 2531 patients undergoing TKR to
• rivaroxaban 10 mg
• or enoxaparin 40 mg once daily
• Enoxaparin was started before surgery, and
  rivaroxaban 68 hours after surgery
• Both were continued for 1014 days

Lassen MR, et al. Presented at ISTH 2007 in
Geneva, Switzerland, abstract O-S-006-B.
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Rivaroxaban An Oral, Direct Factor Xa Inhibitor
for the Prevention of VTE in Total Knee
Replacement Surgery Results of the RECORD 3
Study
Methods

• Primary efficacy outcome
• Venous thromboembolism (VTE) diagnosed by
  mandatory venography
• Symptomatic VTE
• And all-cause mortality
• Primary safety outcome
• Major bleeding

Lassen MR, et al. Presented at ISTH 2007 in
Geneva, Switzerland, abstract O-S-006-B.
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Study Design
Lassen MR, et al. Presented at ISTH 2007 in
Geneva, Switzerland, abstract O-S-006-B.
6
Study Flow
Lassen MR, et al. Presented at ISTH 2007 in
Geneva, Switzerland, abstract O-S-006-B.
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Rivaroxaban An Oral, Direct Factor Xa Inhibitor
for the Prevention of VTE in Total Knee
Replacement Surgery Results of the RECORD 3
Study
Results

• 1254 patients were randomized to rivaroxaban
• 824 were evaluable for primary efficacy outcome
• 1277 patients were randomized to enoxaparin
• 878 were evaluable for primary efficacy outcome

Lassen MR, et al. Presented at ISTH 2007 in
Geneva, Switzerland, abstract O-S-006-B.
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Primary Efficacy Endpoints
Lassen MR, et al. Presented at ISTH 2007 in
Geneva, Switzerland, abstract O-S-006-B.
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Secondary Efficacy Endpoints
Lassen MR, et al. Presented at ISTH 2007 in
Geneva, Switzerland, abstract O-S-006-B.
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Main Safety Endpoints
Lassen MR, et al. Presented at ISTH 2007 in
Geneva, Switzerland, abstract O-S-006-B.
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Bleeding Assessment
n Enoxaparin 40 mg once daily (n1239) Rivaroxaban 10 mg once daily (n1220)
Any bleeding 60 4.8 60 4.9

Major bleeding 6 0.5 7 0.6
Fatal 0 0
Hemorrhagic spinal puncture 2 1
Leading to re-operation 4 5
Leading to fall in hemoglobin 0 1
Leading to transfusion of ?2 units of blood 0 1
Non-major bleeding 54 4.4 53 4.3
Clinically relevant non-major bleeding 28 2.3 33 2.7
Hemorrhagic wound complications 24 25
Other non-major bleeding 31 22
On-treatment bleeding major bleeding events
could qualify for more than one subcategory
event occurred before intake of active drug
extra-surgical-site bleeding composite of
excessive wound hematoma and surgical-site
bleeding safety population, n2459
Lassen MR, et al. Presented at ISTH 2007 in
Geneva, Switzerland, abstract O-S-006-B.
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Rivaroxaban An Oral, Direct Factor Xa Inhibitor
for the Prevention of VTE in Total Knee
Replacement Surgery Results of the RECORD 3
Study
Conclusions

• Rivaroxaban was significantly more effective than
  enoxaparin in the prevention of VTE after TKR in
  this study
• Bleeding was similarly low in both groups
• This study with rivaroxaban is the first
  demonstration of the effectiveness and safety of
  a fixed, unmonitored regimen of an oral Factor Xa
  inhibitor in antithrombotic therapy

Lassen MR, et al. Presented at ISTH 2007 in
Geneva, Switzerland, abstract O-S-006-B.