Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Venous Thrombosis and Pulmonary Embolism 2 - RECORD2

Jul 05, 2008
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Author/Summarized by Author:
Anthony A. Bavry, MD,MPH,FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Bayer HealthCare AG, Johnson & Johnson Pharmaceutical Research and Development LLC
Date Published:
01/01/2008
Date Updated:
07/05/2008
Original Posted Date:
07/05/2008
References

Description:

The goal of the trial was to evaluate extended treatment with the oral direct factor Xa inhibitor rivaroxaban compared with short-term subcutaneous enoxaparin in patients undergoing hip arthroplasty.

Hypothesis:

Extended duration rivaroxaban will be more effective in preventing venous thromboembolism (VTE).

Study Design

  • Randomized
  • Blinded
  • Stratified

Patients Screened: 2,554
Patients Enrolled: 2,509
Mean Follow Up: 30-42 days
Mean Patient Age: 62 years
Female: 54

Patient Populations:

Patients at least 18 years of age scheduled to undergo total hip arthroplasty

Exclusions:

• Need for bilateral total hip arthroplasty
• Pregnant or breast-feeding
• Active bleeding or high risk of bleeding
• Allergy or contraindication to one of the study medications
• Any condition preventing bilateral venography
• Severe liver disease
• Severe renal disease
• Use of protease inhibitors for treatment of human immunodeficiency virus
• Planned intermittent pneumatic compression
• Indication for anticoagulation that does not allow it to be termination

Primary Endpoints:

Composite of all-cause mortality, nonfatal pulmonary embolism, or any DVT (either symptomatic or asymptomatic detected by bilateral venography) at 30-42 days

Secondary Endpoints:

• Major VTE: defined as VTE-related death, nonfatal pulmonary embolism, or proximal DVT
• Incidence of DVT
• Symptomatic VTE during the treatment period and during follow-up

Drug/Procedures Used:

Patients undergoing hip arthroplasty were randomized to 10 mg of oral rivaroxaban once daily beginning after surgery and continued for 31-39 days (n = 1,252) or 40 mg of subcutaneous enoxaparin once daily beginning the evening before surgery and continued for 10-14 days (n = 1,257).

Principal Findings:

The mean duration of therapy was 33.5 days with rivaroxaban and 12.4 days with enoxaparin. History of VTE (for rivaroxaban vs. enoxaparin) was 0.8% versus 1.6%, previous orthopedic surgery was 18.3% versus 18.9%, and the median duration of surgery was 95.0 minutes versus 93.0 minutes.

The primary outcome occurred in 2.0% of the rivaroxaban group and 9.3% of the enoxaparin group (p < 0.0001). Major VTE was 0.6% versus 5.1% (p < 0.0001), death during the treatment period was 0.2% versus 0.7% (p = 0.29), death during follow-up was 0% versus 0.2% (p = 0.50), nonfatal pulmonary embolism was 0.1% versus 0.5% (p = 0.37), any deep vein thrombosis (DVT) was 1.6% versus 8.2% (p <0.0001), symptomatic VTE during treatment was 0.2% versus 1.2% (p = 0.004), and symptomatic VTE during follow-up was 0.1% versus 0.2% (p = 0.62), respectively, for rivaroxaban versus enoxaparin.

Major bleeding occurred in <0.1% of the rivaroxaban group and <0.1% of the enoxaparin group. Any bleeding during treatment was 6.6% versus 5.5%, minor bleeding was 6.5% versus 5.5%, and hemorrhagic wound complication was 1.6% versus 1.7%, respectively. Serious adverse events occurred in 7.3% versus 10.7%, whereas any adverse event occurred in 62.5% versus 65.7%, respectively.

Interpretation:

The use of extended duration rivaroxaban was superior to short-term enoxaparin in preventing VTE after total hip replacement. Rivaroxaban reduced the composite outcome of death, nonfatal pulmonary embolism, or any DVT 30-42 days after surgery. This was driven by a reduction in distal and proximal DVTs, including symptomatic VTE. The incidence of major bleeding and serious adverse events were similar between the rivaroxaban and enoxaparin groups.

RECORD2 confirms the superiority and favorable safety profile of extended duration rivaroxaban (10 mg daily for mean treatment duration of 34 days) compared with short-term enoxaparin. This trial complements the findings of RECORD1 and RECORD3.

References:

Kakkar AK, Brenner B, Dahl OE, et al., on behalf of the RECORD2 Investigators. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet 2008;June 25:[Epub ahead of print].

Keywords: Arthroplasty, Replacement, Hip, Complement System Proteins, Follow-Up Studies, Morpholines, Enoxaparin, Thiophenes, Pulmonary Embolism, Venous Thromboembolism, Venous Thrombosis, Factor Xa, Orthopedics


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