Aspirin or Rivaroxaban for VTE Prophylaxis after Hip or Knee Arthroplasty

This article discusses the prevention of venous thromboembolism (VTE) and is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do or do not outweigh risks, burden, and costs. Grade 2 suggestions imply that individual patient values may lead to different choices (for a full discussion of the grading, see the "Grades of Recommendation" chapter by Guyatt et al). Among the key recommendations in this chapter are the following: we recommend that every hospital develop a formal strategy that addresses the prevention of VTE (Grade 1A). We recommend against the use of aspirin alone as thromboprophylaxis for any patient group (Grade 1A), and we recommend that mechanical methods of thromboprophylaxis be used primarily for patients at high bleeding risk (Grade 1A) or possibly as an adjunct to anticoagulant thromboprophylaxis (Grade 2A). For patients undergoing major general surgery, we recommend thromboprophylaxis with a low-molecular-weight heparin (LMWH), low-dose unfractionated heparin (LDUH), or fondaparinux (each Grade 1A). We recommend routine thromboprophylaxis for all patients undergoing major gynecologic surgery or major, open urologic procedures (Grade 1A for both groups), with LMWH, LDUH, fondaparinux, or intermittent pneumatic compression (IPC). For patients undergoing elective hip or knee arthroplasty, we recommend one of the following three anticoagulant agents: LMWH, fondaparinux, or a vitamin K antagonist (VKA); international normalized ratio (INR) target, 2.5; range, 2.0 to 3.0 (each Grade 1A). For patients undergoing hip fracture surgery (HFS), we recommend the routine use of fondaparinux (Grade 1A), LMWH (Grade 1B), a VKA (target INR, 2.5; range, 2.0 to 3.0) [Grade 1B], or LDUH (Grade 1B). We recommend that patients undergoing hip or knee arthroplasty or HFS receive thromboprophylaxis for a minimum of 10 days (Grade 1A); for hip arthroplasty and HFS, we recommend continuing thromboprophylaxis > 10 days and up to 35 days (Grade 1A). We recommend that all major trauma and all spinal cord injury (SCI) patients receive thromboprophylaxis (Grade 1A). In patients admitted to hospital with an acute medical illness, we recommend thromboprophylaxis with LMWH, LDUH, or fondaparinux (each Grade 1A). We recommend that, on admission to the ICU, all patients be assessed for their risk of VTE, and that most receive thromboprophylaxis (Grade 1A).

VTE is a serious, but decreasing complication following major orthopedic surgery. This guideline focuses on optimal prophylaxis to reduce postoperative pulmonary embolism and DVT. The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. In patients undergoing major orthopedic surgery, we recommend the use of one of the following rather than no antithrombotic prophylaxis: low-molecular-weight heparin; fondaparinux; dabigatran, apixaban, rivaroxaban (total hip arthroplasty or total knee arthroplasty but not hip fracture surgery); low-dose unfractionated heparin; adjusted-dose vitamin K antagonist; aspirin (all Grade 1B); or an intermittent pneumatic compression device (IPCD) (Grade 1C) for a minimum of 10 to 14 days. We suggest the use of low-molecular-weight heparin in preference to the other agents we have recommended as alternatives (Grade 2C/2B), and in patients receiving pharmacologic prophylaxis, we suggest adding an IPCD during the hospital stay (Grade 2C). We suggest extending thromboprophylaxis for up to 35 days (Grade 2B). In patients at increased bleeding risk, we suggest an IPCD or no prophylaxis (Grade 2C). In patients who decline injections, we recommend using apixaban or dabigatran (all Grade 1B). We suggest against using inferior vena cava filter placement for primary prevention in patients with contraindications to both pharmacologic and mechanical thromboprophylaxis (Grade 2C). We recommend against Doppler (or duplex) ultrasonography screening before hospital discharge (Grade 1B). For patients with isolated lower-extremity injuries requiring leg immobilization, we suggest no thromboprophylaxis (Grade 2B). For patients undergoing knee arthroscopy without a history of VTE, we suggest no thromboprophylaxis (Grade 2B). Optimal strategies for thromboprophylaxis after major orthopedic surgery include pharmacologic and mechanical approaches.

Previous trials of antiplatelet therapy for the prevention of venous thromboembolism have individually been inconclusive, but a meta-analysis of their results indicated reductions in the risks of deep-vein thrombosis and of pulmonary embolism in various high-risk groups. The aim of this large randomised placebo-controlled trial was to confirm or refute these apparent benefits. During 1992-1998, 148 hospitals in Australia, New Zealand, South Africa, Sweden and the UK randomised 13,356 patients undergoing surgery for hip fracture, and 22 hospitals in New Zealand randomised a further 4088 patients undergoing elective arthroplasty. Study treatment was 160 mg daily aspirin or placebo, started preoperatively and continued for 35 days. Patients received any other thromboprophylaxis thought necessary. Follow-up was of mortality and of in-hospital morbidity up to day 35. Among the patients with hip fracture, allocation to aspirin produced proportional reductions in pulmonary embolism of 43% (95% CI 18-60; p=0.002) and in symptomatic deep-vein thrombosis of 29% (3-48; p=0.03). Pulmonary embolism or deep-vein thrombosis was confirmed in 105 (1.6%) of 6679 patients assigned aspirin compared with 165 (2.5%) of 6677 assigned placebo, which represents an absolute reduction of 9 (SE 2) per 1000 and a proportional reduction of 36% (19-50; p=0.0003). Similar proportional effects were seen in all major subgroups, including patients receiving subcutaneous heparin. Aspirin prevented 4 (1) fatal pulmonary emboli per 1000 patients (18 aspirin-group vs 43 placebo-group deaths), representing a proportional reduction of 58% (27-76; p=0.002), with no apparent effect on deaths from any other vascular cause (hazard ratio 1.04 [95% CI 0.86-1.26]) or non-vascular cause (1.01 [0.84-1.23]). Deaths due to bleeding were few (13 aspirin vs 15 placebo), but there was an excess of 6 (3) postoperative transfused bleeding episodes per 1000 patients assigned aspirin (p=0.04). Among elective-arthroplasty patients, rates of venous thromboembolism were lower, but the proportional effects of aspirin were compatible with those among patients with hip fracture. These results, along with those of the previous meta-analysis, show that aspirin reduces the risk of pulmonary embolism and deep-vein thrombosis by at least a third throughout a period of increased risk. Hence, there is now good evidence for considering aspirin routinely in a wide range of surgical and medical groups at high risk of venous thromboembolism.