Comparative effectiveness of venous thromboembolism prophylaxis options for the patient undergoing total hip and knee replacement: a network meta‐analysis

Abstract

Summary Background There are numerous trials and several meta-analyses comparing venous thromboembolism (VTE) prophylaxis options after total hip and knee replacement (THR and TKR). None prior included simultaneous comparison of new with older options. Objective To measure simultaneously the relative risk of VTE and hemorrhage for 12 prophylaxis options. Methods We abstracted VTE and hemorrhage information from randomized controlled trials published between January 1990 and June 2016 comparing 12 prophylaxis options. We then constructed networks to compute relative risk for each option relative to low molecular weight heparin at once daily dosing (LMWH Low). Results Main Relative to LMWH Low, direct oral Xa inhibitors had the lowest risk of total DVT - asymptomatic and symptomatic (OR 0.45 95% CI 0.35-0.57) translating to 53 to 139 fewer DVTs per 1000 patients. VKAs titrated to INR 2-3 predicted 56% more DVT events (OR 1.56 95% CI 1.14-2.14). Aspirin performed similarly (OR 0.80 95% CI 0.34-1.86) although small numbers prohibit firm conclusions. direct oral Xa inhibitors did not lead to significantly more bleeding (OR 1.21 95% CI 0.79-1.90). Secondary Relative to LMWH Low, direct oral Xa inhibitors prevented fourfold more symptomatic DVTs (OR 0.25 95% CI 0.13-0.47). Conclusions Relative to LMWH Low, direct oral Xa inhibitors had a more favorable profile of VTE and hemorrhage risk whereas VKAs had a less favorable profile. The profile of other agents was not more or less favorable. Clinicians should consider these profiles when selecting prophylaxis options.

Comparative efficacy and safety of anticoagulants for prevention of venous thromboembolism after hip and knee arthroplasty

“…Kapoor et al. ( 2017 ) performed a comprehensive NMA that included a vitamin K antagonist, aspirin, a mechanical device, and heparin, as well as an oral Xa inhibitor. The oral anticoagulant was analyzed as a single integrated group and it showed a 4-fold decrease in symptomatic VTEs compared with E40, while all other interventions did not show a more favorable profile than E40.…”

“… 2012 , Kapoor et al. 2017 ). However, they did not provide comparison according to the 2 different doses of enoxaparin and did not include edoxaban.…”

Safety and effectiveness of aspirin and enoxaparin for venous thromboembolism prophylaxis after total hip and knee arthroplasty: a systematic review

“…Different from our review, Kapoor et al compared all low‐molecular‐weight heparin (e.g. enoxaparin, dalteparin) with aspirin while we only used enoxaparin as the active comparator . Also, they did not report p ‐scores.…”

“…A previous review performed a comprehensive NMA investigating available RCTs to assess the effectiveness of VTE prophylaxis after THA and TKA . Different from our review, Kapoor et al compared all low‐molecular‐weight heparin (e.g.…”

“…Even though Kapoor et al included more comparative arms and used all low‐molecular‐weight heparin as the active comparator, which made them able to expand their evidence base, they were not able to draw firm conclusions about aspirin. This corresponds with our findings, which showed that the evidence base around aspirin as a VTE prophylaxis is limited.…”