Regulation of Coagulation in Orthopaedic Surgery to Prevent Deep Vein Thrombosis and Pulmonary Embolism 4 - RECORD4

May 07, 2009
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, FACC
Trial Sponsor:
Bayer Schering Pharma AG, and Johnson & Johnson Pharmaceutical Research & Development
Date Published:
01/01/2009
Date Updated:
05/07/2009
Original Posted Date:
05/07/2009
References

Description:

The goal of the trial was to evaluate treatment with the direct factor Xa inhibitor rivaroxaban, compared with enoxaparin after total knee arthroplasty.

Hypothesis:

Rivaroxaban would be noninferior to enoxaparin in preventing deep venous thrombosis (DVT).

Study Design

  • Randomized
  • Blinded
  • Parallel
  • Stratified

Patients Screened: 3,418
Patients Enrolled: 3,148
Mean Follow Up: 17 days
Mean Patient Age: 64 years
Female: 66%

Patient Populations:

  • Patients at least 18 years of age undergoing total knee arthroplasty

Exclusions:

  • Active bleeding or high risk for bleeding
  • Contraindication to enoxaparin
  • Any condition that would prevent bilateral venography
  • Severe liver or renal disease
  • Use of drugs that inhibit cytochrome P450
  • Pregnancy or breast-feeding
  • Planned intermittent pneumatic compression
  • Requirement for chronic anticoagulation

Primary Endpoints:

  • Any DVT, nonfatal PE, or all-cause mortality at 17 days

Secondary Endpoints:

  • Major VTE, nonfatal PE, or death related to VTE
  • Major bleeding
  • Nonmajor bleeding
  • Asymptomatic VTE
  • Symptomatic VTE
  • Death during the follow-up period

Drug/Procedures Used:

After total knee arthroplasty, patients were randomized to oral rivaroxaban 10 mg daily (n = 1,584) versus subcutaneous enoxaparin 30 mg twice daily (n = 1,564). Rivaroxaban was given 6-8 hours after surgery, while enoxaparin was given 12-24 hours after surgery. Mandatory bilateral venography was performed between 11 and 15 days.

Principal Findings:

Overall, 3,148 patients were randomized. The mean age was 64 years, 66% were women, mean body mass index was 31 kg/m2, and 58% had regional anesthesia. The mean time from surgery until the study medication was started was 7 hours in the rivaroxaban group and 17 hours in the enoxaparin group. Study drugs were administered for a mean duration of 11.7 days for the rivaroxaban group and 11.0 days for the enoxaparin group.

The primary efficacy outcome, any DVT, nonfatal pulmonary embolism (PE), or all-cause mortality at 17 days occurred in 6.9% of the rivaroxaban group versus 10.1% of the enoxaparin group (p = 0.012).

Major venous thromboembolism (VTE) was 1.2% versus 2.0% (p = 0.12), death was 0.1% versus 0.2% (p = 0.74), PE was 0.3% versus 0.5% (p = 0.53), and major bleeding was 0.7% versus 0.3% (p = 0.11), respectively, for rivaroxaban versus enoxaparin.

Interpretation:

Among patients undergoing total knee arthroplasty, the use of oral rivaroxaban is superior to subcutaneous enoxaparin in the prevention of any DVT, nonfatal PE, or all-cause mortality. Major bleeding was nonsignificantly increased in the rivaroxaban group. This study complements earlier RECORD trials. A notable difference is the shorter duration of anticoagulation therapy in the present trial (11-12 days) versus approximately 33 days in RECORD1. Accumulating data from these series of studies indicate that rivaroxaban is a safe and convenient drug to prevent VTE after major orthopedic surgery.

References:

Turpie AG, Lassen MR, Davidson BL, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet 2009;373:1673-80.

Keywords: Morpholines, Pulmonary Embolism, Thiophenes, Venous Thromboembolism, Orthopedics, Complement System Proteins, Body Mass Index, Enoxaparin, Phlebography, Venous Thrombosis, Factor Xa


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