Stephen L. Kates, Eduardo Salvati, Lars Gunnar Johnsen.
Response/Recommendation: Hip fracture patients treated with arthroplasty are at higher risk of venous thromboembolism (VTE) and should receive some form of chemothromboprophylaxis. Studies demonstrate that aspirin (ASA) is an effective agent for prevention of VTE in this patient’s population.
Strength of Recommendation: Strong.
Rationale: Hip fracture is one of the most common orthopaedic conditions worldwide, which is associated with 1.7 to 3.6% rate of deep venous thrombosis (DVT), and 1.1% rate of developing pulmonary embolism (PE)1,2. Treatment of the hip fracture with total hip arthroplasty (THA) or hemiarthroplasty (HA) is associated with a higher risk of VTE when compared with treatment by internal fixation (hazard ratio [HR] 2.67, p=0.02)3. Administration of thromboprophylaxis to patients undergoing surgical treatment of hip fracture has been shown to reduce VTE events4. Other studies have questioned the need for routine administration of chemoprophylaxis to these patients and advocated prophylaxis in high-risk populations such as those with a history of VTE, elderly patients (> 75 years), women, and those receiving HA5.
From a timing standpoint, one large registry study has shown superiority of prophylactic treatment with low-molecular-weight heparin (LMWH) beginning preoperatively when compared with postoperative initiation of anticoagulation6. There are very few studies that specifically address chemoprophylaxis in patients undergoing HA or THA for hip fracture. One such study found that the combination of mechanical prophylaxis combined with fondaparinux was superior to fondaparinux prophylaxis alone7. Another study evaluated the role of low-dose ASA for patients with hip fracture undergoing HA or internal fixation and found that administration of low-dose ASA was associated with increased need for blood transfusion and a higher all-cause mortality during the first year after surgery8. However, a meta-analysis comparing ASA vs. other thromboprophylaxis showed a statistically nonsignificant trend favoring other anticoagulants (relative risk [RR]= 1.60). The risk of bleeding was found to be considerably lower when ASA was administered vs. other anticoagulants (RR= 0.32)9. One of the sentinel studies was the Pulmonary Embolism Prevention (PEP) trial that included 13,356 patients with hip fracture receiving ASA vs. placebo. Administration of ASA to hip fracture patients was found to reduce the risk of VTE by a third10.
A recent multi-institutional study evaluated 1,141 patients with femoral neck fracture who underwent THA or HA. Patients were allocated into cohorts based on the type of prophylaxis administered that included ASA (n=454) and other anticoagulants (n=687). The overall VTE rate was 1.98% for patients receiving ASA, compared to 6.7% for patients receiving other anticoagulants (p<0.001). When controlling for potential confounders in the multivariate analysis, ASA was independently associated with a lower risk of VTE (odds ratio [OR] 0.31 95% confidence interval [CI] 0.13-0.65; effect size estimate: -1.17; p=0.003). In addition, patients receiving ASA demonstrated a lower rate of 90 days readmission, and periprosthetic joint infection (PJI). Furthermore, patients administered ASA had a lower rate of allogeneic blood transfusion despite no difference in preoperative hemoglobin levels.
Based on the available literature, it appears that patients with hip fracture undergoing HA or THA are at higher risk of VTE and require prophylaxis. ASA appears to be an effective agent for the prevention of VTE in this patient’s population.
References:
1. Campbell A, Lott A, Gonzalez L, Kester B, Egol KA. Patient-Centered Care: Total Hip Arthroplasty for Displaced Femoral Neck Fracture Does Not Increase Infection Risk. J Healthc Qual. 2020;42(1):27-36. doi:10.1097/JHQ.0000000000000213
2. Warren JA, Sundaram K, Hampton R, Billow D, Patterson B, Piuzzi NS. Venous thromboembolism rates remained unchanged in operative lower extremity orthopaedic trauma patients from 2008 to 2016. Injury. 2019;50(10):1620-1626. doi:10.1016/j.injury.2019.09.003
3. MacDonald DRW, Neilly D, Schneider PS, et al. Venous Thromboembolism in Hip Fracture Patients: A Subanalysis of the FAITH and HEALTH Trials. J Orthop Trauma. 2020;34 Suppl 3:S70-S75. doi:10.1097/BOT.0000000000001939
4. Li Q, Dai B, Xu J, et al. Can patients with femoral neck fracture benefit from preoperative thromboprophylaxis?: A prospective randomized controlled trial. Medicine (Baltimore). 2017;96(29):e7604. doi:10.1097/MD.0000000000007604
5. Lin Y-C, Lee S-H, Chen I-J, et al. Symptomatic pulmonary embolism following hip fracture: A nationwide study. Thromb Res. 2018;172:120-127. doi:10.1016/j.thromres.2018.10.014
6. Leer-Salvesen S, Dybvik E, Dahl OE, Gjertsen J-E, EngesæTer LB. Postoperative start compared to preoperative start of low-molecular-weight heparin increases mortality in patients with femoral neck fractures. Acta Orthop. 2017;88(1):48-54. doi:10.1080/17453674.2016.1235427
7. Tsuda Y, Yasunaga H, Horiguchi H, Fushimi K, Kawano H, Tanaka S. Effects of fondaparinux on pulmonary embolism following hemiarthroplasty for femoral neck fracture: a retrospective observational study using the Japanese Diagnosis Procedure Combination database. J Orthop Sci. 2014;19(6):991-996. doi:10.1007/s00776-014-0607-2
8. Kragh AM, Waldén M, Apelqvist A, Wagner P, Atroshi I. Bleeding and first-year mortality following hip fracture surgery and preoperative use of low-dose acetylsalicylic acid: an observational cohort study. BMC Musculoskelet Disord. 2011;12:254. doi:10.1186/1471-2474-12-254
9. Drescher FS, Sirovich BE, Lee A, Morrison DH, Chiang WH, Larson RJ. Aspirin versus anticoagulation for prevention of venous thromboembolism major lower extremity orthopedic surgery: a systematic review and meta-analysis. J Hosp Med. 2014;9(9):579-585. doi:10.1002/jhm.2224
10. Prevention of pulmonary embolism and deep vein thrombosis with low dose aspirin: Pulmonary Embolism Prevention (PEP) trial. Lancet. 2000;355(9212):1295-1302.