Effect of Aspirin vs Enoxaparin on Symptomatic Venous Thromboembolism in Patients Undergoing Hip or Knee Arthroplasty

Author:

,Sidhu Verinder S.12,Kelly Thu-Lan3,Pratt Nicole3,Graves Stephen E.4,Buchbinder Rachelle56,Adie Sam7,Cashman Kara8,Ackerman Ilana56,Bastiras Durga4,Brighton Roger910,Burns Alexander W. R.11,Chong Beng Hock1213,Clavisi Ornella14,Cripps Maggie12,Dekkers Mark15,de Steiger Richard16,Dixon Michael17,Ellis Andrew1819,Griffith Elizabeth C.8,Hale David20,Hansen Amber12,Harris Anthony21,Hau Raphael1622,Horsley Mark23,James Dugal24,Khorshid Omar25,Kuo Leonard26,Lewis Peter27,Lieu David28,Lorimer Michelle8,MacDessi Samuel729,McCombe Peter30,McDougall Catherine31,Mulford Jonathan32,Naylor Justine Maree12,Page Richard S.33,Radovanovic John34,Solomon Michael35,Sorial Rami36,Summersell Peter37,Tran Phong38,Walter William L.181939,Webb Steve5,Wilson Chris4041,Wysocki David42,Harris Ian A.1243

Affiliation:

1. School of Clinical Medicine, UNSW Medicine and Health, UNSW Sydney, Sydney, New South Wales, Australia

2. Whitlam Orthopaedic Research Centre, Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia

3. Clinical and Health Sciences, Quality Use of Medicines Pharmacy Research Centre, University of South Australia, Adelaide, South Australia, Australia

4. Australian Orthopaedic Association National Joint Replacement Registry, Adelaide, South Australia, Australia

5. Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia

6. Monash-Cabrini Department of Musculoskeletal Health and Clinical Epidemiology, Cabrini Health, Melbourne, Victoria, Australia

7. School of Clinical Medicine, UNSW Medicine and Health, St George and Sutherland Clinical Campuses, Faculty of Medicine and Health, UNSW Sydney, New South Wales, Australia

8. South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia

9. Orthopaedic Department, Westmead Private Hospital, Westmead, Sydney, New South Wales, Australia

10. Orthopaedic Department, Lakeview Private Hospital, Baulkham Hills, Sydney, New South Wales, Australia

11. Orthopaedic Department, Calvary John James Hospital, Deakin, Canberra, Australian Capital Territory, Australia

12. Department of Medicine, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia

13. Department of Hematology, New South Wales Pathology, Kogarah Campus, Sydney, New South Wales, Australia

14. Musculoskeletal Australia, Melbourne, Victoria, Australia

15. Orthopaedic Department, Greenslopes Private Hospital, Greenslopes, Brisbane, Queensland, Australia

16. Department of Surgery, Epworth Healthcare, University of Melbourne, Melbourne, Victoria, Australia

17. Orthopaedic Department, Kareena Private Hospital, Sutherland, Sydney, New South Wales, Australia

18. Orthopaedic Department, Royal North Shore Hospital, St Leonard’s, Sydney, New South Wales, Australia

19. Sydney Musculoskeletal Health Flagship Centre of the University of Sydney and Royal North Shore Hospital, St Leonard’s, Sydney, New South Wales, Australia

20. Orthopaedic Department, Hornsby and Kuringai Hospital, Hornsby, Sydney, New South Wales, Australia

21. Centre for Health Economics, Monash Business School, Monash University, Melbourne, Victoria, Australia

22. Eastern Health Clinical School, Monash University, Box Hill, Victoria, Australia

23. Orthopaedic Department, Royal Prince Alfred Hospital, Camperdown, Sydney, New South Wales, Australia

24. Bendigo Healthcare Group, Bendigo Hospital, Bendigo, Victoria, Australia

25. Orthopaedic Department, Fremantle Hospital, Fremantle, Western Australia, Australia

26. Orthopaedic Department, Canterbury Hospital, Canterbury, Sydney, New South Wales, Australia

27. Orthopaedic Department, Calvary Hospital, Adelaide, South Australia, Australia

28. Orthopaedic Department, Fairfield Hospital, Fairfield, Sydney, New South Wales, Australia

29. Orthopaedic Department, St George Private Hospital, Kogarah, Sydney, New South Wales, Australia

30. Orthopaedic Department, Frankston Hospital, Frankston, Melbourne, Victoria, Australia

31. Orthopaedic Department, The Prince Charles Hospital, Chermside, Brisbane, Queensland, Australia

32. Orthopaedic Department, Launceston General Hospital, Launceston, Tasmania, Australia

33. School of Medicine, St John of God Hospital and Barwon Health, Deakin University, Geelong, Victoria, Australia

34. Orthopaedic Department, Mater Hospital, Raymond Terrace, Brisbane, Queensland, Australia

35. Orthopaedic Department, Prince of Wales Hospital, Randwick, Sydney, New South Wales, Australia

36. Orthopaedic Department, Nepean Hospital, Nepean, Sydney, New South Wales, Australia

37. Orthopaedic Department, Coffs Harbour Base Hospital, Coffs Harbour, New South Wales, Australia

38. Orthopaedic Department, Western Health, Melbourne, Victoria, Australia

39. The Kolling Institute, Faculty of Medicine and Health, The University of Sydney and the Northern Sydney Local Health District, Sydney, New South Wales, Australia

40. Orthopaedic Department, Flinders Medical Centre, Bedford Park, Adelaide, South Australia, Australia

41. Department of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia

42. Orthopaedic Department, Sir Charles Gardiner Hospital, Perth, Western Australia, Australia

43. Institute of Musculoskeletal Health, School of Public Health, The University of Sydney, Sydney, New South Wales, Australia

Abstract

ImportanceThere remains a lack of randomized trials investigating aspirin monotherapy for symptomatic venous thromboembolism (VTE) prophylaxis following total hip arthroplasty (THA) or total knee arthroplasty (TKA).ObjectiveTo determine whether aspirin was noninferior to enoxaparin in preventing symptomatic VTE after THA or TKA.Design, Setting, and ParticipantsCluster-randomized, crossover, registry-nested trial across 31 hospitals in Australia. Clusters were hospitals performing greater than 250 THA or TKA procedures annually. Patients (aged ≥18 years) undergoing hip or knee arthroplasty procedures were enrolled at each hospital. Patients receiving preoperative anticoagulation or who had a medical contraindication to either study drug were excluded. A total of 9711 eligible patients were enrolled (5675 in the aspirin group and 4036 in the enoxaparin group) between April 20, 2019, and December 18, 2020. Final follow-up occurred on August 14, 2021.InterventionsHospitals were randomized to administer aspirin (100 mg/d) or enoxaparin (40 mg/d) for 35 days after THA and for 14 days after TKA. Crossover occurred after the patient enrollment target had been met for the first group. All 31 hospitals were initially randomized and 16 crossed over prior to trial cessation.Main Outcomes and MeasuresThe primary outcome was symptomatic VTE within 90 days, including pulmonary embolism and deep venous thrombosis (DVT) (above or below the knee). The noninferiority margin was 1%. Six secondary outcomes are reported, including death and major bleeding within 90 days. Analyses were performed by randomization group.ResultsEnrollment was stopped after an interim analysis determined the stopping rule was met, with 9711 patients (median age, 68 years; 56.8% female) of the prespecified 15 562 enrolled (62%). Of these, 9203 (95%) completed the trial. Within 90 days of surgery, symptomatic VTE occurred in 256 patients, including pulmonary embolism (79 cases), above-knee DVT (18 cases), and below-knee DVT (174 cases). The symptomatic VTE rate in the aspirin group was 3.45% and in the enoxaparin group was 1.82% (estimated difference, 1.97%; 95% CI, 0.54%-3.41%). This failed to meet the criterion for noninferiority for aspirin and was significantly superior for enoxaparin (P = .007). Of 6 secondary outcomes, none were significantly better in the enoxaparin group compared with the aspirin group.Conclusions and RelevanceAmong patients undergoing hip or knee arthroplasty for osteoarthritis, aspirin compared with enoxaparin resulted in a significantly higher rate of symptomatic VTE within 90 days, defined as below- or above-knee DVT or pulmonary embolism. These findings may be informed by a cost-effectiveness analysis.Trial RegistrationANZCTR Identifier: ACTRN12618001879257

Publisher

American Medical Association (AMA)

Subject

General Medicine

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