Comparison of DOACs and LMWH for Thromboprophylaxis After Total Knee Arthroplasty

Total knee arthroplasty is associated with a substantial risk of venous thromboembolism, and pharmacological thromboprophylaxis is routinely used after surgery. This study aims to compare three thromboprophylaxis strategies and their effects on postoperative venous hemodynamics following primary total knee arthroplasty.

Eligible adults undergoing elective primary unilateral total knee arthroplasty will be enrolled after providing written informed consent. Participants will be randomly assigned to one of three treatment groups: apixaban 2.5 mg twice daily, rivaroxaban 10 mg once daily, or weight-adjusted enoxaparin 40-60 mg once daily. According to the study protocol, patients receive an initial LMWH prophylactic treatment 6 hours after surgery and subsequently receive the randomized thromboprophylaxis regimen 24 hours after surgery. Treatment is planned for 14 days.

The primary objective is to compare peak systolic velocity (PSV) in major lower-limb veins between the three thromboprophylaxis groups using duplex Doppler ultrasound during the 28-day postoperative period. Additional Doppler parameters will include time-averaged mean velocity, vessel diameter, venous flow volume, respiratory phasicity, distal augmentation, and visible intraluminal sludging.

Secondary assessments will include postoperative rehabilitation, level of immobilization, articular stiffness, range of motion, static and dynamic pain, postoperative bleeding, anticoagulation-related adverse effects or overdose, suspected venous thromboembolism, return to the operating room, infections, and other postoperative complications.

Doppler assessments will be performed at baseline and on Days 7, 15, 21, and 28. The Doppler examiner will be blinded to the assigned anticoagulation regimen. Measurements will be performed using spectral Doppler ultrasound at the common femoral and popliteal veins.

The study plans to recruit at least 138 participants, with a minimum of 46 participants in each treatment group. The sample size was calculated to detect a 15% difference in the mean peak systolic velocity of the common femoral vein, with a two-sided alpha level of 0.05 and 80% statistical power.

• Apixaban (Drug): Apixaban 2.5 mg twice daily, starting 24 hours after surgery, for 14 days. Participants receive initial LMWH prophylaxis 6 hours after surgery before starting the assigned regimen.
• Rivaroxaban (Drug): Rivaroxaban 10 mg once daily, starting 24 hours after surgery, for 14 days. Participants receive initial LMWH prophylaxis 6 hours after surgery before starting the assigned regimen.
• Enoxaparin (LMWH) (Drug): Enoxaparin 40-60 mg once daily, weight-adjusted, starting 6 hours after surgery, for 14 days.

Primary outcomes

• Mean Peak Systolic Velocity of the Common Femoral Vein at Postoperative Days 0, 7, 15, 21, and 28 [Postoperative day 0 through day 28.]: Peak systolic velocity (PSV) of the common femoral vein will be measured using duplex Doppler ultrasound at baseline (postoperative day 0) and on postoperative days 7, 15, 21, and 28. Results will be expressed in centimeters per second (cm/s) and summarized as mean and standard deviation at each time point for the three thromboprophylaxis groups: apixaban 2.5 mg twice daily, rivaroxaban 10 mg once daily, and enoxaparin once daily. The mean PSV will be compared between groups.

Secondary outcomes

• Mean Time-Averaged Mean Velocity of the Common Femoral and Popliteal Veins [Within 28 days after surgery]: Time-averaged mean blood flow velocity will be measured separately in the common femoral and popliteal veins by duplex Doppler ultrasound at postoperative days 0, 7, 15, 21, and 28. Results will be expressed in centimeters per second (cm/s) and summarized as mean and standard deviation for each vein, treatment group, and time point.
• Mean Diameter of the Common Femoral and Popliteal Veins [Within 28 days after surgery]: The diameter of the common femoral vein and popliteal vein will be measured separately by duplex Doppler ultrasound at postoperative days 0, 7, 15, 21, and 28. Results will be expressed in millimeters (mm) and summarized as mean and standard deviation for each vein, treatment group, and time point.
• Mean Venous Blood Flow Volume in the Common Femoral and Popliteal Veins [Within 28 days after surgery]: Venous blood flow volume will be measured separately in the common femoral and popliteal veins by duplex Doppler ultrasound at postoperative days 0, 7, 15, 21, and 28. Results will be expressed in \[confirmed unit\] and summarized as mean and standard deviation for each vein, treatment group, and time point.
• Number of Participants with Normal Respiratory Phasicity in the Common Femoral and Popliteal Veins [Within 28 days after surgery]: Respiratory phasicity will be assessed separately in the common femoral and popliteal veins at postoperative days 0, 7, 15, 21, and 28. Findings will be classified as normal or reduced/blunted. The number and percentage of participants with normal respiratory phasicity will be reported for each vein, treatment group, and time point.
• Number of Participants with Preserved Distal Venous Flow Augmentation [Within 28 days after surgery]: Distal venous flow augmentation will be assessed separately in the common femoral and popliteal veins at postoperative days 0, 7, 15, 21, and 28 and classified as present or absent. The number and percentage of participants with augmentation present will be reported for each vein, treatment group, and time point.
• Number of Participants with Visible Intraluminal Venous Sludging [Days 7, 15, 21, and 28]: Visible intraluminal venous sludging will be assessed separately in the common femoral and popliteal veins by duplex Doppler ultrasound. Findings will be classified as present or absent. The number and percentage of participants with visible sludging will be reported for each vein, treatment group, and assessment time point.
• Number of Participants with Postoperative Complications [During the 28-day follow-up]: The number and percentage of participants experiencing clinically relevant postoperative bleeding, anticoagulation-related adverse events or overdose, suspected venous thromboembolism, return to the operating room, or postoperative infection will be reported during the 28-day follow-up. Each complication will be reported separately.
• Number of Participants with Postoperative Cardiovascular Complications [During the 28-day follow-up]: The number and percentage of participants experiencing cardiovascular complications during the 28-day postoperative follow-up will be reported. The specific cardiovascular events assessed will be defined according to the study protocol.

Sex: All, ages: 18 Years to 80 Years

Inclusion Criteria:

* Adults aged 18 years or older undergoing elective primary unilateral total knee arthroplasty.
* Able to provide informed consent.

Exclusion Criteria:

* Allergy or contraindication to the study medications.
* Requirement for long-term therapeutic anticoagulation.
* Requirement for antiplatelet therapy.
* Pregnancy or lactation.
* Active cancer or cancer treatment.
* Documented previous venous thromboembolism in the target limb.
* Hypercoagulable state.
* BMI >40 kg/m².
* Severe inflammatory disease.
* Age >80 years.
* Inability to comply with follow-up.
* Incomplete data.