Bilateral vs. ipsilateral venography as the primary efficacy outcome measure in thromboprophylaxis clinical trials: a systematic review

Abstract

Summary. Contrast venography, in combination with symptomatic venous thromboembolism (VTE), is the standard efficacy outcome measure in clinical trials of thromboprophylaxis in major orthopedic surgery. It is uncertain whether performing bilateral venography offers any real advantage over venography of the operated leg alone. This study was undertaken to determine the risk of isolated contralateral deep vein thrombosis (DVT) following major orthopedic surgery and to evaluate whether bilateral venography, rather than venography on the operated leg alone, offers any gain in DVT detection and, thereby, improves efficiency in clinical study design. A systematic review of prospective studies that reported DVT incidence as the primary efficacy outcome based on mandatory bilateral venography in patients undergoing elective hip or knee arthroplasty or hip fracture repair was conducted. Based on the use of bilateral venography as a primary efficacy outcome measure, the incidence of any DVT is 16.7% following total hip replacement, 18.8% after hip fracture repair, and 33.8% after total knee replacement. While DVT risk in the operated leg varies depending on the type of surgery, the risk of isolated DVT in the non-operated leg is approximately 4% to 5% in all three procedures. By increasing the detection of any DVT, the use of bilateral venography reduces required sample size by 16% to 25% compared to ipsilateral venography. In clinical trials evaluating the efficacy of thromboprophylaxis in major orthopedic surgery, bilateral venography reduces the risk of undiagnosed DVT in the non-operated leg and improves the efficiency of study design by substantially reducing the sample size requirement.

Evaluation of Deep Vein Thrombosis with Multidetector Row CT after Orthopedic Arthroplasty: a Prospective Study for Comparison with Doppler Sonography

“…However, the risk of an isolated DVT in the non-operated leg is approximately 4% to 5% (11). In the clinical trials that aimed at evaluating the efficacy of thromboprophylaxis for major orthopedic surgery, bilateral venography was noted to reduce the risk of undiagnosed DVT in the non-operated leg (11). …”

“…The diagnostic modalities for detecting the DVT that develops after total joint replacement includes conventional venography (11, 12), Doppler sonography (1-3,13-26), MR venography (27) and radionuclide venography (28). Compared with conventional venography, Doppler sonography has the advantage of being portable, painless and noninvasive, there are no side effects and it is a less expensive screening and surveillance tool for managing DVT (13).…”

A randomized evaluation of betrixaban, an oral factor Xa inhibitor, for prevention of thromboembolic events after total knee replacement (EXPERT)

“…Another factor which may have contributed to the lower event rate was the choice of unilateral venography on the operated leg rather than bilateral venography. On the other hand, the large majority of DVTs occur in the operated extremity (15), hence the choice of unilateral venography in the current study in an attempt to minimize patient discomfort and procedural risks. As expected, the majority of VTEs were distal DVTs identified from mandatory venography on Day 10 to 14 of the study.…”

Microsurgery and the Hypercoagulable State

“…Both mutations are relatively weak risk factors in the heterozygous state; the relative risk of venous thromboembolism they confer is similar to that reported for combination oral contraceptive use 50 and is dwarfed by the risk of venous thromboembolism associated with major surgery. 51,52 Thus, the contribution of these genotypes to postoperative venous thromboembolism is likely to be small. Deficiencies of protein C, protein S, and antithrombin and factor V Leiden homozygosity and factor V Leiden/ prothrombin G20210A compound heterozygosity are associated with a greater risk of venous thromboembolism, but are considerably rarer (Table 1).…”