Antithrombotic Treatment With Factor XIa Inhibition to Optimize Management of Acute Thromboembolic Events in Total Knee Replacement - AXIOMATIC-TKR

Nov 15, 2021
Font Size
A
A
A
Author/Summarized by Author:
Anthony A. Bavry, MD,MPH,FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, FACC, MBA
Trial Sponsor:
Bristol Myers Squibb; Janssen Research and Development
Date Presented:
11/15/2021
Date Published:
11/15/2021
Original Posted Date:
11/15/2021
References

Contribution To Literature:

The AXIOMATIC-TKR trial showed that milvexian was beneficial at preventing venous thromboembolism after knee arthroplasty compared with enoxaparin.

Description:

The goal of the trial was to evaluate oral milvexian compared with subcutaneous enoxaparin among patients undergoing elective knee arthroplasty. Milvexian is a potent inhibitor of factor XIa, which is absorbed 2-4 hours after oral administration and has a half-life of 8-14 hours.

Study Design

  • Randomization
  • Parallel
  • Open-label

Participants undergoing elective knee arthroplasty were randomized to: milvexian 25 mg daily (n = 34) vs. milvexian 50 mg daily (n = 150) vs. milvexian 200 mg daily (n = 149) vs. milvexian 25 mg twice daily (n = 153) vs. milvexian 50 mg twice daily (n = 150) vs. milvexian 100 mg twice daily (n = 152) vs. milvexian 200 mg twice daily (n = 153) vs. enoxaparin 40 mg daily (n = 301).

  • Total number of enrollees: 1,242
  • Duration of follow-up: 14 days
  • Mean patient age: 69 years
  • Percentage female: 71%

Inclusion criteria:

  • Patients ≥18 years of age undergoing elective knee arthroplasty

Principal Findings:

The primary efficacy outcome, venous thromboembolism (asymptomatic deep vein thrombosis on mandatory unilateral venogram on days 10-14, symptomatic venous thromboembolism, or death), occurred at a rate of:

  • 25.0% in the milvexian 25 mg daily group
  • 23.6% in the milvexian 50 mg daily group
  • 6.5% in the milvexian 200 mg daily group

(p = 0.0003 for combined daily group vs. enoxaparin)

  • 20.9% in the milvexian 25 mg twice daily group
  • 11.3% in the milvexian 50 mg twice daily group
  • 9.0% in the milvexian 100 mg twice daily group
  • 7.6% in the milvexian 200 mg twice daily group

(p = 0.0004 for combined twice daily group vs. enoxaparin)

  • 21.4% in the enoxaparin 40 mg daily group

The primary safety outcome, any bleeding (composite of major [ISTH criteria], clinically relevant nonmajor, and minor bleeding), occurred at a rate of 4.1% in the milvexian group vs. 4.1% in the enoxaparin group.

Interpretation:

Among patients undergoing elective knee arthroplasty, the factor XIa inhibitor milvexian was effective at preventing venous thromboembolism compared with enoxaparin in this phase 2 randomized clinical trial. Milvexian was associated with a low rate of any bleeding, which was similar to the enoxaparin group.

References:

Weitz JI, Strony J, Ageno W, et al., on behalf of the AXIOMATIC-TKR Investigators. Milvexian for the Prevention of Venous Thromboembolism. N Engl J Med 2021;Nov 15:[Epub ahead of print].

Presented by Dr. Jeffrey I. Weitz at the American Heart Association Virtual Annual Scientific Sessions (AHA 2021), November 15, 2021.

Clinical Topics: Anticoagulation Management, Dyslipidemia, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Anticoagulation Management and Venothromboembolism, Lipid Metabolism, Novel Agents

Keywords: AHA Annual Scientific Sessions, AHA21, Anticoagulants, Arthroplasty, Replacement, Knee, Elective Surgical Procedures, Enoxaparin, Factor XIa, Hemorrhage, Primary Prevention, Vascular Diseases, Venous Thromboembolism, Venous Thrombosis


< Back to Listings