Harman Chaudhry MD MSc1, and Mitch Winemaker MD FRCSC2 1 Division of Orthopaedic Surgery, Department of Surgery, University of Toronto, Toronto, ON, Canada 2 Division of Orthopaedic Surgery, Department of Surgery, McMaster University, Hamilton, ON, Canada Thromboembolic disease – specifically PE and deep vein thrombosis (DVT) – was once a common and morbid complication following TKA. The combination of iatrogenic surgical trauma, immobilization, and venous stasis (the so‐called Virchow’s triad) result in the formation of clots in the deep veins of the lower extremity, some of which migrate to the pulmonary circulation, potentially leading to fatal pulmonary disease. The introduction of prophylactic anticoagulation following TKA substantially reduced the incidence of thromboembolic disease in the lower extremities.1 However, PE remains a dreaded, albeit infrequent, postoperative complication. Ongoing research has endeavored to determine the optimal prophylactic regimen to prevent thromboembolism following TKA. There are several available options for the prophylaxis of thromboembolic disease following TKA. Mechanical prophylaxis includes the use of lower extremity pneumatic compression devices or continuous passive motion (CPM) to prevent venous stasis and the subsequent development of DVT. Chemoprophylaxis has traditionally involved the use of warfarin (i.e. a vitamin K antagonist), acetylsalicylic acid (ASA), heparin, or low‐molecular‐weight heparin (LMWH). Newer pharmacologic agents, referred to as direct oral anticoagulants or DOACs, are gaining widespread acceptance due to their perceived efficacy and convenience (i.e. oral administration, no requirement for weekly monitoring, etc.). DOACs include agents which directly inhibit thrombin or clotting factors (e.g. factor Xa inhibitors). The optimal choice has remained elusive. Two competing issues have led to substantial controversy over the years. The need to prevent thromboembolism, including asymptomatic DVT, figured prominently in the first set of clinical guidelines on thromboembolism prophylaxis developed by the American College of Chest Physicians (ACCP).2 On the contrary, concerns regarding clinically important bleeding complications (e.g. hematoma, wound healing complications, etc.) in addition to the prevention of PE (but not necessarily asymptomatic DVT) were important considerations in the initial guidelines developed by the American Academy of Orthopaedic Surgeons (AAOS).2 Owing to these differences, some of the recommendations issued by each association, particularly pertaining to the use of ASA and other pharmacologic prophylactic agents, were in direct conflict with one another.3 The most recent guidelines, however, are more concordant and have resolved major conflicts.4,5 There are multiple randomized controlled trials (RCTs) addressing the topic of older (or traditional) prophylactic options (i.e. mechanical prophylaxis, warfarin, heparin, and LMWHs), as well as several methodologically robust systematic reviews and meta‐analyses.6,7 Similar quality evidence exists comparing newer‐generation anticoagulants to other newer‐generation anticoagulants.8,9 The most thorough quantitative summary of the latter is provided by a network meta‐analysis comparing venous thromboembolism and major bleeding amongst six common prophylactic anticoagulants: fondaparinux, dabigatran, rivaroxaban, apixaban, edoxaban, and enoxaparin.8 The use of ASA for thromboembolism prophylaxis instead of anticoagulants has been the subject of controversy,10 but it has also been the explored in several RCTs and a meta‐analysis.11 The meta‐analysis evaluated eight RCTs comparing ASA versus anticoagulants in 1408 patients undergoing surgery for hip fracture, hip arthroplasty, or knee arthroplasty along with subgroup analyses conducted in each subcategory. Collectively, the available literature on these comparisons represents level I evidence. The use of a mechanical prophylaxis devices alone (i.e. intermitted pneumatic leg compression) does not prevent the risk of DVT as effectively as if an anticoagulant is added to this regimen (risk ratio [RR] = 0.52; 95% confidence interval [CI]: 0.33–0.82).6 The risk of PE, or major or minor bleeding, is no different between regimens. The use of CPM devices after TKA has also been investigated in terms of preventing venous thromboembolism. A Cochrane review found that there was no advantage to the use of CPM in preventing venous thromboembolism after TKA (RR = 1.22; 95% CI: 0.85–1.79).7 In a network meta‐analysis, LMWH was compared to DOACs (and various DOACs were compared to one another).8 The following DOACs were found to decrease the odds of venous thromboembolism as compared to enoxaparin (i.e. LMWH): apixaban (odds ratio [OR] = 0.59; 95% CI: 0.42–0.84), fondaparinux (OR = 0.47; 95% CI: 0.33–0.65), rivaroxaban (OR = 0.41; 95% CI: 0.30–0.58), and edoxaban (OR = 0.45; 95% CI: 0.24–0.84). Fondaparinux and rivaroxaban were found to increase the odds of major bleeding in comparison to LMWH (OR = 1.46; 95% CI: 1.05–2.03 and OR = 1.28; 95% CI: 1.04–1.57, respectively), whereas apixaban appeared to decrease the odds of major bleeding (OR = 0.82; 95% CI: 0.69–0.98). Importantly, the authors noted that all trials informing these conclusions were vulnerable to unclear or high risk of bias, and all were industry‐sponsored trials.8
48 Venous Thromboembolism in Total Knee Arthroplasty
Clinical scenario
Top three questions
Question 1: In patients undergoing TKA, are newer generation anticoagulants superior to older agents for venous thromboembolism prophylaxis?
Rationale
Clinical comment
Available literature and quality of the evidence
Findings
Mechanical prophylaxis
DOACs
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